A Phase 1 interventional study of L9LS and Placebo in Malaria, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 3 sites in Mali. Open to participants aged 1 Month to 12 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-01.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of L9LS in infants in Mali and to evaluate the impact of L9LS on subsequent R21/Matrix-MTM vaccine immunogenicity.
This is an age-stratified, randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics (PK) of one-time intramuscular (IM) administration of the monoclonal antibody (MAb) L9LS to healthy Malian infants aged 1 to 12 months, followed by an assessment of the impact of L9LS on the immunogenicity of subsequent administration of the R21/Matrix-MTM vaccine. The study hypotheses are that L9LS will be safe and will not impact the immunogenicity of the R21/Matrix-MTM vaccine. During the beginning of the 6-month malaria season (approximately August and September at the study site), 180 participants will be enrolled and randomized 1:1 to receive 150 mg of L9LS (n=90) or normal saline placebo (n=90). Randomization of participants in each arm will be age-stratified (1 to 4 months, n=60; >4 to 8 months, n=60; >8 to 12 months, n=60). The safety of L9LS will be assessed within each of the three (3) age strata. Participants will be followed at study visits 1, 3, 7, 14, 21, and 28 days later, and once every 4 weeks thereafter through study day 280 (40 weeks). Approximately 5 months after receiving L9LS or placebo, all participants will receive the R21/Matrix-MTM vaccine as 3 total doses given 4 weeks apart as per World Health Organization (WHO) recommendations and the anticipated Malian vaccination guidelines.
Primary study assessments include medical history, physical examination, and blood collection to assess antibody responses to the R21/Matrix-MTM vaccine, L9LS PK, anti-drug antibody (ADA) assessments, identification of Plasmodium falciparum (Pf) infection by microscopic examination of thick blood smears and reverse transcription polymerase chain reaction (RT-PCR), and other research laboratory evaluations. Through their local provider, all participants 3 months and older will be offered 4 rounds of seasonal malaria chemoprevention (SMC) as a monthly 3-day treatment course of sulfadoxine-Pyrimethamine plus amodiaquine (SPAQ), as it is the standard of care in Mali for malaria prevention in children 3 months to 5 years of age.
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's enrollment of 327 is above the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) 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.
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.
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.
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.
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.
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).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
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.
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.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
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.
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.
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.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
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.
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.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Infants age 1-4 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Biological: L9LS · Biological: R21/Matrix-MTM
Infants age 5-8 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Biological: L9LS · Biological: R21/Matrix-MTM
Infants age 9-12 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Biological: L9LS · Biological: R21/Matrix-MTM
Infants age 1-4 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Other: Placebo · Biological: R21/Matrix-MTM
Infants age 5-8 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Other: Placebo · Biological: R21/Matrix-MTM
Infants age 9-12 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Other: Placebo · Biological: R21/Matrix-MTM
Administered intramuscularly one time.
Normal Saline administered intramuscularly one time.
Administered intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
Participants With Local Adverse Events (AEs)
Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion. Adverse events were captured by Investigator examination and history from participants.
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)
Severity of Local Adverse Events (AEs)
The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness=Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis Grade 5: Death
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)
Participants With Systemic Adverse Events (AEs)
Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants.
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)
Severity of Systemic Adverse Events (AEs)
The severity of systemic AEs after the administration of L9LS or placebo was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock Grade 5: Death
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)
Participants With Adverse Events of Special Interest (AESIs) Related to R21/Matrix-MTM Vaccine
Number of participants with Adverse events of special interest (AESIs), which is described as hypersensitivity reaction within seven days of receiving each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196). Adverse events of special interest (AESIs) are study-specific events that are of particular concern due to population, study intervention, class effect, etc. A Type III hypersensitivity reaction associated with the administration of the R21/Matrix-MTM vaccine are characterized by symptoms such as fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked discomfort, and/or dyspnea.
Time frame: Within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196)
Severity of Adverse Events of Special Interest (AESIs)
The severity of adverse events of special interest (AESIs) occurring within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196) was graded using the table below. Participants with multiple episodes of same adverse event across grades were counted separately according to adverse event grade. Grade 1: Mild signs and symptoms Grade 2: Moderate signs and symptoms AND intervention indicated (e.g., antihistamines) Grade 3: Severe signs and symptoms AND higher level intervention indicated (e.g., steroids or IV fluids) Grade 4: Life-threatening consequences (e.g., requiring pressor or ventilator support)
Time frame: Within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196)
Antibody Response to R21/Matrix-MTM Vaccine
The antibody response to the R21/Matrix-M was assessed as the total anti-Asn-Ala-Asn-Pro (anti-NANP) immunoglobulin G (IgG) ((anti-NANP IgG)) antibody titers. The total IgG anti-NANP antibody titers was measured by electrochemiluminescence immunoassay (ECLIA), using the Meso Scale Discovery LLC-based automation platform on serum samples collected 28 days (day 224) and 84 days (day 280) after the third dose of R21/Matrix-MTM vaccination. Outcomes analyzed as concentration of antibody titers of the polyclonal antibody response in a serum sample. Concentration is expressed in arbitrary units per milliliter (AU/mL), which are assigned based on a sample's relative binding as compared to an established serum reference standard.
Time frame: Measured 28 days (Day 224) and 84 days (Day 280) after the third dose of R21/Matrix-MTM vaccination
Maximum Total Plasma Concentration (Cmax) for L9LS
Maximum total plasma concentration (Cmax) following a dose of 150 mg L9LS. Serum was collected on days 0, 7, 28, 84, 140, 196, and 280 after the administration of L9LS. Cmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles post dose. Analysis was done to determine each participant's maximum observed concentration based on all available data points and cumulative output was calculated as the central tendency and dispersion metric based on the observed maximum concentrations.
Time frame: Days 0 to 280
Time to Maximum Plasma Concentration (TMax) for L9LS
Time to maximum total plasma concentration (Tmax) following a dose of 150 mg or 300 mg L9LS. Serum was collected on days 0, 7, 28, 84, 140, 196, \& 280 after administration of L9LS. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in days) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration.
Time frame: Days 0 to 280
Area Under the Curve (AUC) for L9LS From Day 0 to 168 (AUC_168)
Plasma area under the concentration time curve (AUC) for L9LS from day 0 to day 168. Data for day 168 was interpolated using observed concentrations. Non-compartmental analysis was performed using the linear-up/log-down trapezoidal rule with the PKNCA package in R.
Time frame: Days 0 to 280
Area Under the Curve (AUC) From Day 0 to Last Observed for L9LS
The area under the concentration time curve from day 0 to the last observed concentration (in days) was calculated using the linear-up/log-down trapezoidal rule by non-compartmental analysis with the PKNCA package in R.
Time frame: Days 0 to 280
Area Under the Concentration Time Curve (AUC) From Day 0 to Infinity
The area under the concentration time curve (AUC) from day 0 to infinity, extrapolated from the last observed concentration, was calculated using the linear-up/log-down trapezoidal rule by non-compartmental analysis with the PKNCA package in R.
Time frame: Days 0 to 280
Terminal Half-life (t½) of L9LS
The terminal half-life was determined by non-compartmental analysis using the PKNCA package in R, which fits the natural logarithm of concentration by time using a minimum of four observed data points in the terminal phase, not including the maximum total plasma concentration (Cmax).
Time frame: Days 0 to 280
Participants With Detectable Anti-drug Antibody (ADA) in Sera
Number of participants with detectable anti-drug antibody (ADA) in sera after exposure to L9LS. Serum was collected from participants at baseline (enrollment), days 28, 224, and 280. The tier 3 assay was used to directly measure ADA's ability to impair L9LS binding to Plasmodium falciparum circumsporozoite protein (PfCSP). Analysis was done to determine number of participants with positive or detectable ADA in sera.
Time frame: Baseline (enrollment), days 28, 224, and 280
Participants With Plasmodium Falciparum (Pf) Detected by Microscopic Examination
Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by microscopic examination of thick blood smear collected at various time points (day 7, 28, 84, 140, 196, 224, and 280) from participants from day 7 through day 280 after administration of L9LS or placebo. Analysis was done as number of participants who had at least one positive blood smear.
Time frame: Measured days 7, 28, 84, 140, 196, 224, and 280
| Milestone | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Started | 30 | 30 | 30 | 30 | 30 | 30 |
| Has day 7 data | 30 | 30 | 30 | 30 | 30 | 30 |
| Completed three doses of r21/matrix-mtm vaccine | 29 | 30 | 30 | 29 | 29 | 29 |
| Completed | 29 | 29 | 30 | 29 | 30 | 28 |
| Not completed | 1 | 1 | 0 | 1 | 0 | 2 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 | 0 | 0 | 2 |
| Withdrew: Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 1 | 0 | 0 |
Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion. Adverse events were captured by Investigator examination and history from participants.
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Injection site swelling | 0 | 0 | 1 | 0 | 0 | 0 |
| Pain at Injection site | 0 | 0 | 0 | 0 | 0 | 0 |
| Tenderness at injection site | 0 | 0 | 0 | 0 | 0 | 0 |
| Redness at injection site | 0 | 0 | 0 | 0 | 0 | 0 |
| Bruising at injection site | 0 | 0 | 0 | 0 | 0 | 0 |
| Pruritus at injection site | 0 | 0 | 0 | 0 | 0 | 0 |
The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness=Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis Grade 5: Death
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Grade 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Grade 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 5 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants.
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Fever | 4 | 1 | 1 | 1 | 2 | 1 |
| Feeling unusually tired or unwell | 0 | 0 | 0 | 0 | 0 | 0 |
| Muscle aches | 0 | 0 | 0 | 0 | 0 | 0 |
| Headache | 0 | 0 | 0 | 0 | 0 | 0 |
| Chills | 0 | 0 | 0 | 0 | 0 | 0 |
| Nausea | 0 | 0 | 0 | 0 | 0 | 0 |
| Joint pain | 0 | 0 | 0 | 0 | 0 | 0 |
The severity of systemic AEs after the administration of L9LS or placebo was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock Grade 5: Death
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Grade 1 | 3 | 1 | 1 | 1 | 2 | 1 |
| Grade 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Grade 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 5 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of participants with Adverse events of special interest (AESIs), which is described as hypersensitivity reaction within seven days of receiving each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196). Adverse events of special interest (AESIs) are study-specific events that are of particular concern due to population, study intervention, class effect, etc. A Type III hypersensitivity reaction associated with the administration of the R21/Matrix-MTM vaccine are characterized by symptoms such as fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked discomfort, and/or dyspnea.
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Fever | 12 | 17 | 12 | 12 | 14 | 13 |
| Arthralgia | 0 | 0 | 0 | 0 | 0 | 0 |
| Myalgia | 0 | 0 | 0 | 0 | 0 | 0 |
| Skin eruptions | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphadenopathy | 0 | 0 | 0 | 0 | 0 | 0 |
| Marked discomfort | 0 | 0 | 0 | 0 | 0 | 0 |
| Dyspnea | 0 | 0 | 0 | 0 | 0 | 0 |
The severity of adverse events of special interest (AESIs) occurring within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196) was graded using the table below. Participants with multiple episodes of same adverse event across grades were counted separately according to adverse event grade. Grade 1: Mild signs and symptoms Grade 2: Moderate signs and symptoms AND intervention indicated (e.g., antihistamines) Grade 3: Severe signs and symptoms AND higher level intervention indicated (e.g., steroids or IV fluids) Grade 4: Life-threatening consequences (e.g., requiring pressor or ventilator support)
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Grade 1 | 7 | 9 | 15 | 11 | 10 | 14 |
| Grade 2 | 6 | 4 | 3 | 4 | 3 | 0 |
| Grade 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 4 | 0 | 0 | 0 | 0 | 0 | 0 |
The antibody response to the R21/Matrix-M was assessed as the total anti-Asn-Ala-Asn-Pro (anti-NANP) immunoglobulin G (IgG) ((anti-NANP IgG)) antibody titers. The total IgG anti-NANP antibody titers was measured by electrochemiluminescence immunoassay (ECLIA), using the Meso Scale Discovery LLC-based automation platform on serum samples collected 28 days (day 224) and 84 days (day 280) after the third dose of R21/Matrix-MTM vaccination. Outcomes analyzed as concentration of antibody titers of the polyclonal antibody response in a serum sample. Concentration is expressed in arbitrary units per milliliter (AU/mL), which are assigned based on a sample's relative binding as compared to an established serum reference standard.
| AU/mL | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Day 224 | 627,356 (480,611 to 818,906) | 514,960 (424,176 to 625,174) | 549,101 (441,519 to 682,898) | 759,875 (621,405 to 929,200) | 785,729 (568,157 to 1,086,619) | 572,639 (462,602 to 708,851) |
| Day 280 | 261,888 (200,903 to 341,384) | 248,437 (198,574 to 310,821) | 272,566 (214,208 to 346,823) | 385,661 (311,209 to 477,924) | 413,062 (281,023 to 607,140) | 337,537 (259,931 to 438,314) |
Maximum total plasma concentration (Cmax) following a dose of 150 mg L9LS. Serum was collected on days 0, 7, 28, 84, 140, 196, and 280 after the administration of L9LS. Cmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles post dose. Analysis was done to determine each participant's maximum observed concentration based on all available data points and cumulative output was calculated as the central tendency and dispersion metric based on the observed maximum concentrations.
| μg/mL | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Maximum Total Plasma Concentration (Cmax) for L9LS | 268.48 ± 41.94 | 232.93 ± 30.76 | 209.46 ± 32.74 |
Time to maximum total plasma concentration (Tmax) following a dose of 150 mg or 300 mg L9LS. Serum was collected on days 0, 7, 28, 84, 140, 196, \& 280 after administration of L9LS. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in days) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration.
| Days | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Time to Maximum Plasma Concentration (TMax) for L9LS | 7.03 ± 0.19 | 7.00 ± 0.00 | 7.03 ± 0.18 |
Plasma area under the concentration time curve (AUC) for L9LS from day 0 to day 168. Data for day 168 was interpolated using observed concentrations. Non-compartmental analysis was performed using the linear-up/log-down trapezoidal rule with the PKNCA package in R.
| (μg/mL)*days | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Area Under the Curve (AUC) for L9LS From Day 0 to 168 (AUC_168) | 14822.76 ± 2549.00 | 12442.15 ± 1909.58 | 10727.96 ± 1794.07 |
The area under the concentration time curve from day 0 to the last observed concentration (in days) was calculated using the linear-up/log-down trapezoidal rule by non-compartmental analysis with the PKNCA package in R.
| (μg/mL)*days | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Area Under the Curve (AUC) From Day 0 to Last Observed for L9LS | 15355.09 ± 2695.02 | 12901.47 ± 1986.48 | 11108.00 ± 1859.41 |
The area under the concentration time curve (AUC) from day 0 to infinity, extrapolated from the last observed concentration, was calculated using the linear-up/log-down trapezoidal rule by non-compartmental analysis with the PKNCA package in R.
| (μg/mL)*days | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Area Under the Concentration Time Curve (AUC) From Day 0 to Infinity | 15426.53 ± 2715.86 | 12992.26 ± 1993.20 | 11177.57 ± 1913.85 |
The terminal half-life was determined by non-compartmental analysis using the PKNCA package in R, which fits the natural logarithm of concentration by time using a minimum of four observed data points in the terminal phase, not including the maximum total plasma concentration (Cmax).
| Days | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Terminal Half-life (t½) of L9LS | 34.346 ± 2.829 | 36.485 ± 4.203 | 35.331 ± 3.099 |
Number of participants with detectable anti-drug antibody (ADA) in sera after exposure to L9LS. Serum was collected from participants at baseline (enrollment), days 28, 224, and 280. The tier 3 assay was used to directly measure ADA's ability to impair L9LS binding to Plasmodium falciparum circumsporozoite protein (PfCSP). Analysis was done to determine number of participants with positive or detectable ADA in sera.
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg |
|---|---|---|---|
| Baseline (enrollment) | 0 | 0 | 0 |
| Day 28 | 0 | 0 | 0 |
| Day 224 | 0 | 0 | 0 |
| Day 280 | 0 | 0 | 0 |
Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by microscopic examination of thick blood smear collected at various time points (day 7, 28, 84, 140, 196, 224, and 280) from participants from day 7 through day 280 after administration of L9LS or placebo. Analysis was done as number of participants who had at least one positive blood smear.
| Participants | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo |
|---|---|---|---|---|---|---|
| Participants With Plasmodium Falciparum (Pf) Detected by Microscopic Examination | 1 | 3 | 2 | 7 | 6 | 9 |
Collected over Up to day 280 from initial study intervention administration. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Infants 1-4 Months: L9LS 150 mg | 0/30 (0%) | 1/30 (3.3%) | 30/30 (100%) |
| Infants 5-8 Months: L9LS 150 mg | 1/30 (3.3%) | 1/30 (3.3%) | 30/30 (100%) |
| Infants 9-12 Months: L9LS 150 mg | 0/30 (0%) | 0/30 (0%) | 30/30 (100%) |
| Infants 1-4 Months: Placebo | 0/30 (0%) | 0/30 (0%) | 30/30 (100%) |
| Infants 5-8 Months: Placebo | 0/30 (0%) | 2/30 (6.7%) | 30/30 (100%) |
| Infants 9-12 Months: Placebo | 0/30 (0%) | 0/30 (0%) | 30/30 (100%) |
| R21/Matrix-MTM Vaccine | 0/177 (0%) | 0/177 (0%) | 83/177 (46.9%) |
| Event | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | R21/Matrix-MTM Vaccine |
|---|---|---|---|---|---|---|---|
| IntussusceptionGastrointestinal disorders | 0/30 | 0/30 | 0/30 | 0/30 | 1/30 | 0/30 | 0/177 |
| Encephalitis viralInfections and infestations | 1/30 | 0/30 | 0/30 | 0/30 | 0/30 | 0/30 | 0/177 |
| GastroenteritisInfections and infestations | 0/30 | 0/30 | 0/30 | 0/30 | 1/30 | 0/30 | 0/177 |
| DrowningGeneral disorders | 0/30 | 1/30 | 0/30 | 0/30 | 0/30 | 0/30 | 0/177 |
| Event | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | R21/Matrix-MTM Vaccine |
|---|---|---|---|---|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 27/30 | 21/30 | 22/30 | 20/30 | 23/30 | 24/30 | 0/177 |
| RhinitisInfections and infestations | 20/30 | 20/30 | 20/30 | 15/30 | 20/30 | 24/30 | 0/177 |
| DiarrhoeaGastrointestinal disorders | 16/30 | 22/30 | 21/30 | 20/30 | 23/30 | 18/30 | 3/177 |
| Upper respiratory tract infectionInfections and infestations | 7/30 | 8/30 | 9/30 | 7/30 | 16/30 | 2/30 | 0/177 |
| PyrexiaGeneral disorders | 10/30 | 10/30 | 14/30 | 12/30 | 11/30 | 8/30 | 80/177 |
| TachycardiaCardiac disorders | 3/30 | 3/30 | 7/30 | 5/30 | 11/30 | 7/30 | 0/177 |
| VomitingGastrointestinal disorders | 7/30 | 11/30 | 9/30 | 7/30 | 8/30 | 4/30 | 3/177 |
| NeutropeniaBlood and lymphatic system disorders | 7/30 | 7/30 | 1/30 | 9/30 | 6/30 | 3/30 | 0/177 |
| TeethingGastrointestinal disorders | 4/30 | 6/30 | 8/30 | 4/30 | 8/30 | 7/30 | 0/177 |
| MalariaInfections and infestations | 1/30 | 3/30 | 2/30 | 7/30 | 5/30 | 8/30 | 0/177 |
| Age, Customized(Participants) | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | Total |
|---|---|---|---|---|---|---|---|
| 1-4 months | 30 | 0 | 0 | 30 | 0 | 0 | 60 |
| 5-8 months | 0 | 30 | 0 | 0 | 30 | 0 | 60 |
| 9-12 months | 0 | 0 | 30 | 0 | 0 | 30 | 60 |
| Sex: Female, Male(Participants) | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Female | 12 | 15 | 12 | 13 | 10 | 19 | 81 |
| Male | 18 | 15 | 18 | 17 | 20 | 11 | 99 |
| Race/Ethnicity, Customized(Participants) | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Black | 30 | 30 | 30 | 30 | 30 | 30 | 180 |
| Region of Enrollment(participants) | Infants 1-4 Months: L9LS 150 mg | Infants 5-8 Months: L9LS 150 mg | Infants 9-12 Months: L9LS 150 mg | Infants 1-4 Months: Placebo | Infants 5-8 Months: Placebo | Infants 9-12 Months: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Mali | 30 | 30 | 30 | 30 | 30 | 30 | 180 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Human data generated in this study for future research will be shared as follows: De-identified or identified data with approved outside collaborators under appropriate agreements. De-identified results or data in publication and/or public presentations.
Supporting information: Study protocol
Time frame: Data will be shared at the time of publication or shortly thereafter.
Access criteria: Data from this study may be requested from other researchers indefinitely after the completion of the primary endpoint by contacting Laboratory of Immunogenetics.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Institute of Allergy and Infectious Diseases (NIAID) →