A Phase 3 interventional study of pyronaridine artesunate and arthemeter lumefantrine in Malaria, sponsored by Medicines for Malaria Venture. Completed at 8 sites in 8 countries. Open to participants aged Up to 12 Years. Per ClinicalTrials.gov, last updated 2021-11-22.
Sponsored by Medicines for Malaria Venture · Phase 3, Interventional, and Treatment
The primary objective of this Phase III clinical study is to demonstrate the efficacy of the fixed combination of pyronaridine artesunate (PA) granule formulation (60:20 mg; pediatric PYRAMAX®) by showing a PCR-corrected adequate clinical and parasitological cure rate (ACPR) of more than 90%.
Secondary objectives of this clinical study are to compare the efficacy (non-inferiority) and safety of the PA granule formulation compared to Coartem® (ie, the combination of artemether/lumefantrine [AL]) crushed tablets in a paediatric population and to assess the safety of the PA granule formulation.
This is a multi-centre, comparative, randomised, open-label, parallel-group study of the efficacy and safety of a 3-day regimen of a fixed combination of PA (3:1) versus AL in the treatment of acute uncomplicated Plasmodium falciparum mono-infection. The study population will include 534 patients, comprising male and female infants and children (body weight ≥5 and \<25 kg) recruited from study sites in East, Central, and West Africa and South East Asia (max. 150 patients/site).
Patients will be randomised in a 2:1 ratio to receive either oral PA (60:20 mg granules) once a day for 3 consecutive days (Days 0, 1, and 2) or AL (20:120 mg crushed tablets) twice a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third Party Investigator unblinded to the study treatment, while the Investigator will remain blinded. For PA, the dose range covered by this regimen is 7.0:2.3 mg to 13.3:4.4 mg, which has been shown to be effective and safe in Phase I and II studies. Posology will be based on body weight ranges for both the PA and AL regimens.
Patients will be confined to the study facility ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs earlier.
The primary efficacy end point for this study is the proportion of subjects with PCR-corrected ACPR on Day 28. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 535 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →Medicines for Malaria Venture is the lead sponsor of 66 studies on the registry; 3 are open to participants now.
Compared within Malaria, Falciparum, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Malaria. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
Exclusion Criteria:
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.
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.
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.
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.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
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.
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.
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.
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.
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.
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.
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.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
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.
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.
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.
Oral pyronaridine/artesunate (PA, 60:20mg granules) once a day for 3 consecutive days (Days 0, 1, and 2). Posology based on body weight ranges.
Drug: pyronaridine artesunate
Oral artemether/lumefantrine (AL, 20:120mg crushed tablets) twice a day for 3 consecutive days (Days 0, 1, and 2). Posology based on body weight ranges.
Drug: arthemeter lumefantrine
The strength of the granule formulation is 60:20 mg pyronaridine artesunate per sachet. Depending on their body weight, patients will receive between 1 to 3 pyronaridine artesunate sachets per day, for 3 consecutive days The actual dose-range covered by this regimen is 7.0:2.3 mg/kg to 13.3:4.4 mg/kg pyronaridine artesunate, which has shown to be effective and safe in the phase II studies conducted in children and adults.
Also known as: Pyramax
The strength of the tablet is 20 mg artemether and 120 mg lumefantrine. Depending on their body weight, patients will receive either 1 or 2 crushed tablets twice a day (≥5 to \<15 = 1 tablet, 15 to \<25 kg = 2 tablets), for 3 consecutive days.
Also known as: Coartem
Percentage of Participants With PCR-Corrected ACPR on Day 28
Percentage of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. The PCR-corrected ACPR on Day 28 is defined as the absence of parasitaemia on Day 28 without the patient's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time frame: Day 28
Percentage of Participants With PCR-Corrected ACPR on Day 14
Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 14. The PCR-corrected ACPR on Day 14 is defined as the absence of parasitaemia on Day 14 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time frame: Day 14
Crude ACPR (Non-PCR Corrected ACPR) (Crude Cure Rate) on Day 14 and Day 28
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Day 14 and 28, without correction by PCR. Crude ACPR on Day 14 and 28 is defined as the absence of parasitaemia on Day 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time frame: Days 14 and 28
Parasite Clearance Time
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
Time frame: Days 0, 3, 7, 14, 21, 28, 35, and 42 or on any other day if the subject spontaneously returned within the 42-day study period
Fever Clearance Time
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Time frame: Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit and as clinically indicated (within the 42-day study period)
Proportion of Subjects With Cleared Parasites on Days 1, 2, and 3
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
Time frame: Days 1, 2, and 3
Proportion of Subjects With Fever Cleared on Days 1, 2, and 3
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
Time frame: Days 1, 2, and 3
Number of Subjects With ≥1 Adverse Event
Time frame: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier
| Milestone | PA Group | AL Group |
|---|---|---|
| Started | 355 | 180 |
| Completed | 274 | 142 |
| Not completed | 81 | 38 |
| Withdrew: Adverse event | 6 | 3 |
| Withdrew: Withdrawal by subject | 2 | 2 |
| Withdrew: Lost to follow-up | 6 | 1 |
| Withdrew: Parasite reappearance/malaria | 67 | 32 |
Percentage of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. The PCR-corrected ACPR on Day 28 is defined as the absence of parasitaemia on Day 28 without the patient's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
| percentage of cured subjects | PA Group | AL Group |
|---|---|---|
| Percentage of Participants With PCR-Corrected ACPR on Day 28 | 97.6 (95.4 to 99.0) | 98.8 (95.7 to 99.9) |
Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 14. The PCR-corrected ACPR on Day 14 is defined as the absence of parasitaemia on Day 14 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Percentage of Participants With PCR-Corrected ACPR on Day 14 | 100.0 (98.9 to 100.0) | 100.0 (97.8 to 100.0) |
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Day 14 and 28, without correction by PCR. Crude ACPR on Day 14 and 28 is defined as the absence of parasitaemia on Day 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Percentage of Participants with ACPR at Day 14 | 100 (98.9 to 100.0) | 100 (97.8 to 100.0) |
| Percentage of Participants with ACPR at Day 28 | 90.2 (86.5 to 93.2) | 89.2 (83.5 to 93.5) |
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
| hours | PA Group | AL Group |
|---|---|---|
| Parasite Clearance Time | 24.1 (24.0 to 24.1) | 24.2 (24.0 to 31.8) |
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
| hours | PA Group | AL Group |
|---|---|---|
| Fever Clearance Time | 8.1 (8.0 to 8.1) | 8.1 (8.0 to 15.8) |
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Percentage of Participants with parasite clearance at Day 1 (24h after first dose) | 49.9 (44.5 to 55.2) | 43.7 (36.2 to 51.2) |
| Percentage of Participants with parasite clearance at Day 2 (48h after first dose) | 95.5 (93.3 to 97.8) | 95.2 (92.0 to 98.4) |
| Percentage of Participants with parasite clearance at Day 3 (72h after first dose) | 97.0 (95.2 to 98.8) | 98.8 (97.2 to 100.0) |
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Percentage of Participants with fever clearance at Day 1 (24h after first dose) | 87.1 (83.1 to 91.2) | 81.0 (74.1 to 87.8) |
| Percentage of Participants with fever clearance at Day 2 (48h after first dose) | 98.5 (97.0 to 100.0) | 96.8 (93.8 to 99.9) |
| Percentage of Participants with fever clearance at Day 3 (48h after first dose) | 99.6 (98.9 to 100.0) | 98.4 (96.2 to 100.0) |
| Participants | PA Group | AL Group |
|---|---|---|
| Nr subj. with ≥1 AE | 285 | 143 |
| Nr subj. with ≥1 treatment-related AE | 132 | 80 |
| Nr subj. with ≥1 SAE | 1 | 0 |
| Nr subj. with ≥1 treatment-related SAE | 0 | 0 |
| Nr subj. with ≥1 severe or life-threatening AE | 2 | 2 |
| Nr subj. with ≥1 AE leading to death | 0 | 0 |
| Nr subj. ≥1 AE leading to drug discontinuation | 6 | 3 |
| Nr subj. with ≥1 AE leading to study withdrawal | 6 | 3 |
Collected over Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PA Group | 0/355 (0%) | 1/355 (0.3%) | 285/355 (80.3%) |
| AL Group | 0/180 (0%) | 0/180 (0%) | 143/180 (79.4%) |
| Event | PA Group | AL Group |
|---|---|---|
| MalariaInfections and infestations | 1/355 | 0/180 |
| Event | PA Group | AL Group |
|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 44/355 | 28/180 |
| Upper respiratory tract infectionInfections and infestations | 42/355 | 19/180 |
| Platelet count increasedInvestigations | 33/355 | 19/180 |
| Blood glucose decreasedInvestigations | 32/355 | 19/180 |
| AnaemiaBlood and lymphatic system disorders | 34/355 | 14/180 |
| Blood albumin decreasedInvestigations | 21/355 | 16/180 |
| BronchitisInfections and infestations | 28/355 | 10/180 |
| VomitingGastrointestinal disorders | 25/355 | 8/180 |
| PyrexiaGeneral disorders | 23/355 | 8/180 |
| Influenza like illnessGeneral disorders | 19/355 | 8/180 |
| Age, Continuous(years) | PA Group | AL Group | Total |
|---|---|---|---|
| Mean | 4.9 ± 2.47 | 5.3 ± 2.52 | 5.0 ± 2.49 |
| Age, Customized(Participants) | PA Group | AL Group | Total |
|---|---|---|---|
| <1 year | 12 | 3 | 15 |
| 1-<5 years | 148 | 69 | 217 |
| 5-12 years | 195 | 108 | 303 |
| Sex: Female, Male(Participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Female | 178 | 96 | 274 |
| Male | 177 | 84 | 261 |
| Race/Ethnicity, Customized(Participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Black | 342 | 172 | 514 |
| Asian/Oriental | 13 | 8 | 21 |
| Region of Enrollment(participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Gabon | 53 | 27 | 80 |
| Burkina Faso | 19 | 9 | 28 |
| Mali | 86 | 44 | 130 |
| Philippines | 13 | 7 | 20 |
| Congo, The Democratic Republic of the | 56 | 28 | 84 |
| Côte D'Ivoire | 72 | 35 | 107 |
| Kenya | 56 | 30 | 86 |
The record gives a start of Oct 2007, a primary completion of Sep 2008 and a completion of Nov 2008. It does not say whether these dates are actual or estimated.
Results were first posted in Nov 2021, 13 years 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.
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Medicines for Malaria Venture