A Phase 2 interventional study of Ferroquine SSR97193 and Artefenomel in Plasmodium Falciparum Infection, sponsored by Sanofi. Terminated at 12 sites in 7 countries. Open to participants aged 6 Months to 69 Years. Per ClinicalTrials.gov, last updated 2022-03-24.
Sponsored by Sanofi · Phase 2, Interventional, and Treatment
Primary Objective:
To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.
Secondary Objectives:
To evaluate the efficacy of OZ439/FQ:
Total duration was 63 days for each participant.
Sanofi is the lead sponsor of 1,557 studies on the registry; 91 are open to participants now.
Of its 205 completed or terminated interventional studies of FDA-regulated products, 123 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Male or female participant aged greater than (>) 6 months old and \<70 years old:
Body weight >=5 kg and \<=90 kg.
Presence of mono-infection by Plasmodium falciparum with:
form signed by the participant or by the legally acceptable representative of the minor participant.
Exclusion criteria:
Presence of severe malaria.
Anti-malarial treatment:
Known history or evidence of disorders.
Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-glycoprotein substrates, Cytochrome P450 (CYP) 2D6 main substrates and/or strong CYP2C or inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.
Mixed plasmodium infection.
Severe vomiting.
Severe malnutrition.
Laboratory parameters with clinically significant abnormalities and/or reaching critical values. For Liver Function Test. (>2 [] ULN), or alanine aminotransferase (>2 ULN) or total >1.5 ULN.
Presence of Hepatitis A Immunoglobulin M, surface antigen or antibody.
Had received an drug within the past 4 weeks.
Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.
Measles and yellow fever vaccine injection within the last 15 days and or planned for the 28 days after randomization.
Female participant of child bearing potential not willing to use an effective (s) method(s) for the duration of the study.
Positive serum or urine beta-human chorionic gonadotropin pregnancy test at study screening for female participants of .
Breastfeeding women.
Male participant having a partner of child bearing potential not willing to use an effective method of birth control during the study treatment period.
Splenectomized participants or presence of surgical scar on left hypochondrium. Participant unable to drink.
Known history of , allergic or anaphylactoid reactions to ferroquine or other amino-quinolines or to OZ439 or OZ277 or to any of the .
Family history of sudden death or of congenital prolongation of the (QTc) interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval e.g., participants with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.
QTc using Fridericia's formula >450 millisecond at screening or pre-dose.
Hypokalemia (\<3.5 millimoles per liter [mmol/L]), hypocalcemia (\<2.0 mmol/L) or hypomagnesemia (\<0.5 mmol/L) at screening or pre-dose.
Any treatment known to induce a lengthening of QT interval.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams \[mg\]) oral suspension as follows: BW greater than or equal to (\>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW \>=24 kg to less than (\<) 35 kg: FQ 300 mg + OZ439 600 mg; BW \>=15 kg to \<24 kg: FQ 200 mg + OZ439 400 mg; BW \>=10 kg to \<15 kg: FQ 150 mg + OZ439 300 mg; BW \>=7 kg to \<10 kg: FQ 100 mg + OZ439 200 mg; \>=5 kg to \<7kg: FQ 75 mg + OZ439 150 mg.
Drug: Ferroquine SSR97193 · Drug: Artefenomel · Other: Placebo
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW \>= 35 kg: FQ 600 mg + OZ439 800 mg; BW \>=24 kg to \<35 kg: FQ 450 mg + OZ439 600 mg; BW \>=15 kg to \<24 kg: FQ 300 mg + OZ439 400 mg; BW \>=10 kg to \<15 kg: FQ 225 mg + OZ439 300 mg; BW \>=7 kg to \<10 kg: FQ 150 mg + OZ439 200 mg; \>=5 kg to \<7kg: FQ 115 mg + OZ439 150 mg.
Drug: Ferroquine SSR97193 · Drug: Artefenomel · Other: Placebo
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW \>= 35 kg: FQ 900 mg + OZ439 800 mg; BW \>=24 kg to \<35 kg: FQ 675 mg + OZ439 600 mg; BW \>=15 kg to \<24 kg: FQ 450 mg + OZ439 400 mg; BW \>=10 kg to \<15 kg: FQ 335 mg + OZ439 300 mg; BW \>=7 kg to \<10 kg: FQ 225 mg + OZ439 200 mg; \>=5 kg to \<7kg: FQ 170 mg + OZ439 150 mg.
Drug: Ferroquine SSR97193 · Drug: Artefenomel · Other: Placebo
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW \>= 35 kg: FQ 1200 mg + OZ439 800 mg; BW \>=24 kg to \<35 kg: FQ 900 mg + OZ439 600 mg; BW \>=15 kg to \<24 kg: FQ 600 mg + OZ439 400 mg; BW \>=10 kg to \<15 kg: FQ 450 mg + OZ439 300 mg; BW \>=7 kg to \<10 kg: FQ 300 mg + OZ439 200 mg; \>=5 kg to \<7kg: FQ 225 mg + OZ439 150 mg.
Drug: Ferroquine SSR97193 · Drug: Artefenomel · Other: Placebo
Pharmaceutical form:Capsules Route of administration: oral
Pharmaceutical form:Granules for suspension Route of administration: oral
Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.
Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \>Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5 degree Celsius (°C); or parasite count on Day 3\>=25 percent (%) on Day 0, or late clinical failure(LCF):DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT\>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time frame: Day 28
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28)
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time frame: Day 28
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time frame: Day 28
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42)
ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT \>=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time frame: Day 42
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63)
ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT \>=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time frame: Day 63
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population
ACPR was defined as negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28 or, LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish re-infection (new clone of parasite) or recrudescence.
Time frame: Day 28
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population
ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT \>=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT \<37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time frame: Day 42
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population
Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT \>=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time frame: Day 63
Time to Re-emergence
Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time frame: Up to Day 63
Time to Recrudescence
Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time frame: Up to Day 63
Time to Re-infection
Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time frame: Up to Day 63
Parasite Clearance Time (PCT): African <=5 Years PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time frame: From the start of study drug administration up to the time of the first negative film (up to Day 63)
Parasite Clearance Time: African >5 Years PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time frame: From the start of study drug administration up to the time of the first negative film (up to Day 63)
Parasite Clearance Time: Asian PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time frame: From the start of study drug administration up to the time of the first negative film (up to Day 63)
Fever Clearance Time (FCT): African <=5 Years PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first assessment. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time frame: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Fever Clearance Time: African >5 Years PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time frame: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Fever Clearance Time: Asian PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time frame: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time frame: 24 and 48 hours post dose
Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time frame: 24 and 48 hours post dose
Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time frame: 24 and 48 hours post dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of the first dose of double-blind drug administration up to the Day 63. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Time frame: From Baseline up to Day 63
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel
Cmax is the maximum observed plasma concentration of artefenomel.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel
Area under the plasma concentration versus time curve from time zero to infinity.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)
Cmax is the maximum observed plasma concentration of Ferroquine.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine
Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Time frame: 2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose
Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213
Time frame: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Study conducted at 12 active sites in 7 countries. Total of 806 participants were screened between 25 July 2015 and 22 July 2019, of which 377 were randomized to 1 of 4 treatment arms (via Integrated Web Recognition System using permuted block randomization schedules). 429 participants failed screening mainly due to meeting exclusion criteria.
| Milestone | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Started | 93 | 94 | 97 | 93 |
| Treated | 92 | 94 | 96 | 91 |
| Cohort 1: >14 years to <70 years | 14 | 15 | 18 | 16 |
| Cohort 2: >5 years to <=14 years | 6 | 5 | 6 | 5 |
| Cohort 3: >2 years to <=5 years | 66 | 66 | 67 | 65 |
| Cohort 4: >6 months to <=2 years | 7 | 8 | 6 | 7 |
| Completed | 27 | 37 | 48 | 46 |
| Not completed | 66 | 57 | 49 | 47 |
| Withdrew: Met >=1 anti-malarial treatment criteria | 57 | 51 | 39 | 41 |
| Withdrew: Participant's request | 2 | 3 | 4 | 1 |
| Withdrew: Investigator's judgement | 1 | 0 | 0 | 2 |
| Withdrew: Adverse event | 3 | 1 | 4 | 1 |
| Withdrew: Lost to follow-up | 1 | 1 | 0 | 1 |
| Withdrew: Other unspecified | 1 | 1 | 2 | 0 |
| Withdrew: Not eligible | 1 | 0 | 0 | 1 |
ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \>Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5 degree Celsius (°C); or parasite count on Day 3\>=25 percent (%) on Day 0, or late clinical failure(LCF):DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT\>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28) | 78.4 (64.7 to 88.7) | 85.0 (73.4 to 92.9) | 89.5 (78.5 to 96.0) | 91.7 (81.6 to 97.2) |
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28) | 72.7 (39.0 to 94.0) | 100 (69.2 to 100) | 100 (73.5 to 100) | 90.0 (55.5 to 99.7) |
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28) | 25.0 (0.6 to 80.6) | 25.0 (0.6 to 80.6) | 40.0 (5.3 to 85.3) | 20.0 (0.5 to 71.6) |
ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT \>=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42) | 69.8 (53.9 to 82.8) | 81.8 (69.1 to 90.9) | 84.0 (70.9 to 92.8) | 87.7 (76.3 to 94.9) |
ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT \>=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63) | 64.1 (47.2 to 78.8) | 76.7 (61.4 to 88.2) | 81.8 (67.3 to 91.8) | 87.2 (74.3 to 95.2) |
ACPR was defined as negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT \>=37.5°C between Day 4 and 28 or, LPF: presence of parasitemia between Day 7 and 28 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish re-infection (new clone of parasite) or recrudescence.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population | 49.3 (37.0 to 61.6) | 71.6 (59.3 to 82.0) | 76.2 (63.8 to 86.0) | 87.1 (76.1 to 94.3) |
ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT \>=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT \<37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population | 39.1 (27.6 to 51.6) | 50.8 (38.1 to 63.4) | 61.0 (47.4 to 73.5) | 68.9 (55.7 to 80.1) |
Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \> Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5°C; or parasite count on Day 3 \>=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT \>=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT \<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
| percentage of participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population | 35.3 (24.1 to 47.8) | 46.2 (33.7 to 59.0) | 57.6 (44.1 to 70.4) | 58.3 (44.9 to 70.9) |
Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
| days | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Time to Re-emergence | 36.0 (24.00 to 63.00) | 61.0 (43.00 to NA) | NA (NA to NA) | 64.0 (63.00 to 65.00) |
Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
| days | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Time to Recrudescence | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
| days | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Time to Re-infection | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | 65.0 (NA to NA) |
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Parasite Clearance Time (PCT): African <=5 Years PP Population | 36.0 (24.23 to 36.07) | 36.0 (35.93 to 36.10) | 36.1 (36.00 to 48.00) | 36.1 (24.25 to 36.42) |
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Parasite Clearance Time: African >5 Years PP Population | 24.0 (18.00 to 24.18) | 24.3 (18.07 to 36.00) | 24.3 (12.23 to 36.00) | 27.2 (6.15 to 36.17) |
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Parasite Clearance Time: Asian PP Population | 82.0 (79.97 to NA) | 75.1 (53.93 to 95.82) | 79.8 (36.00 to NA) | 72.2 (60.08 to 79.98) |
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first assessment. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Fever Clearance Time (FCT): African <=5 Years PP Population | 1.0 (1.00 to 24.00) | 1.0 (1.00 to 18.00) | 1.0 (NA to NA) | 1.0 (1.00 to 12.00) |
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Fever Clearance Time: African >5 Years PP Population | 1.0 (1.00 to 18.00) | 1.0 | 1.5 (1.00 to 2.00) | 2.0 |
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature \<37.5°C, confirmed by second assessment, taken within \>=6 to \<=12 hours of the first. Only participants with fever (adjusted body temperature \>=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
| hours | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Fever Clearance Time: Asian PP Population | 18.0 | — | — | 36.0 |
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
| ratio | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| PRR24 (log10) | 2.867 (1.19 to 5.35) | 3.011 (1.10 to 5.63) | 2.397 (1.25 to 4.75) | 2.587 (1.52 to 5.24) |
| PRR48 (log10) | 5.734 (2.39 to 10.69) | 6.023 (2.20 to 11.27) | 4.794 (2.50 to 9.50) | 5.174 (3.04 to 10.48) |
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
| ratio | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| PRR24 (log10) | 2.979 (2.41 to 4.30) | 4.069 (2.16 to 5.00) | 3.288 (2.30 to 4.81) | 3.054 (1.76 to 5.59) |
| PRR48 (log10) | 5.957 (4.83 to 8.60) | 8.137 (4.32 to 10.00) | 6.577 (4.61 to 9.63) | 6.108 (3.52 to 11.17) |
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
| ratio | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| PRR24 (log10) | 1.167 (1.01 to 1.28) | 1.125 (1.00 to 1.44) | 1.688 (1.07 to 3.12) | 1.353 (1.10 to 1.65) |
| PRR48 (log10) | 2.335 (2.03 to 2.56) | 2.250 (1.99 to 2.88) | 3.377 (2.14 to 6.24) | 2.705 (2.21 to 3.31) |
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of the first dose of double-blind drug administration up to the Day 63. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
| Participants | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Any TEAE | 84 | 87 | 85 | 81 |
| Any treatment-emergent SAE | 0 | 2 | 4 | 2 |
| Any treatment-emergent AESI | 5 | 8 | 9 | 11 |
| Any TEAE led to treatment discontinuation | 3 | 2 | 3 | 2 |
| Any TEAE led to death | 0 | 0 | 0 | 0 |
Cmax is the maximum observed plasma concentration of artefenomel.
| nanograms per milliliter | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel | 1072 ± 95 | 936.7 ± 91 | 771.8 ± 92 | 797.8 ± 119 |
Area under the plasma concentration versus time curve from time zero to infinity.
| micrograms*hour per milliliter | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel | 14.24 ± 124 | 12.41 ± 127 | 9.621 ± 130 | 9.605 ± 147 |
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
No measurements were reported for this outcome.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
No measurements were reported for this outcome.
Cmax is the maximum observed plasma concentration of Ferroquine.
| nanograms per milliliter | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax) | 148.1 ± 52 | 222.8 ± 66 | 350 ± 55 | 467.6 ± 80 |
Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
| micrograms*hour per milliliter | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine | 14.92 ± 40 | 22.56 ± 48 | 33.84 ± 48 | 46.4 ± 52 |
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
No measurements were reported for this outcome.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over From Baseline up to Day 63. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | 0/92 (0%) | 0/92 (0%) | 77/92 (83.7%) |
| Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | 0/94 (0%) | 2/94 (2.1%) | 79/94 (84%) |
| Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | 0/96 (0%) | 4/96 (4.2%) | 77/96 (80.2%) |
| Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) | 0/91 (0%) | 2/91 (2.2%) | 74/91 (81.3%) |
| Event | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| Alanine Aminotransferase IncreasedInvestigations | 0/92 | 0/94 | 2/96 | 0/91 |
| Hepatitis AInfections and infestations | 0/92 | 0/94 | 0/96 | 1/91 |
| Pneumonia AspirationRespiratory, thoracic and mediastinal disorders | 0/92 | 0/94 | 0/96 | 1/91 |
| MalariaInfections and infestations | 0/92 | 1/94 | 1/96 | 0/91 |
| PharyngitisInfections and infestations | 0/92 | 1/94 | 0/96 | 0/91 |
| Drug-Induced Liver InjuryHepatobiliary disorders | 0/92 | 0/94 | 1/96 | 0/91 |
| Event | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) |
|---|---|---|---|---|
| MalariaInfections and infestations | 55/92 | 50/94 | 40/96 | 41/91 |
| VomitingGastrointestinal disorders | 27/92 | 27/94 | 34/96 | 34/91 |
| Upper Respiratory Tract InfectionInfections and infestations | 7/92 | 6/94 | 17/96 | 10/91 |
| CoughRespiratory, thoracic and mediastinal disorders | 10/92 | 7/94 | 15/96 | 15/91 |
| DiarrhoeaGastrointestinal disorders | 10/92 | 11/94 | 7/96 | 11/91 |
| PyrexiaGeneral disorders | 7/92 | 2/94 | 9/96 | 10/91 |
| Electrocardiogram Qt ProlongedInvestigations | 6/92 | 5/94 | 6/96 | 8/91 |
| Decreased AppetiteMetabolism and nutrition disorders | 5/92 | 8/94 | 5/96 | 5/91 |
| RhinitisInfections and infestations | 4/92 | 3/94 | 1/96 | 7/91 |
| Abdominal PainGastrointestinal disorders | 7/92 | 5/94 | 5/96 | 6/91 |
Analysis was performed on all randomized participants.
| Age, Continuous(years) | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) | Total |
|---|---|---|---|---|---|
| Mean | 7.34 ± 9.94 | 6.97 ± 8.97 | 7.61 ± 9.60 | 7.68 ± 10.44 | 7.40 ± 9.71 |
| Age, Customized(Participants) | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) | Total |
|---|---|---|---|---|---|
| >6 months to <=2 years | 7 | 8 | 6 | 7 | 28 |
| >2 to <=5 years | 66 | 66 | 67 | 65 | 264 |
| >5 to <=14 years | 6 | 5 | 6 | 5 | 22 |
| >14 to <18 years | 6 | 5 | 7 | 4 | 22 |
| >=18 years | 8 | 10 | 11 | 12 | 41 |
| Sex: Female, Male(Participants) | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) | Total |
|---|---|---|---|---|---|
| Female | 37 | 46 | 43 | 56 | 182 |
| Male | 56 | 48 | 54 | 37 | 195 |
| Race (NIH/OMB)(Participants) | Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) | Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 4 | 5 | 6 | 6 | 21 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 89 | 89 | 91 | 87 | 356 |
| White | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Studies of the drug tested here: Artefenomel