MalariaPhase 1NCT06461026
L9LS MAb in Malian Infants
A Phase 1 study testing L9LS and R21/Matrix-MTM in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in Mali.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 month to 12 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- L9LS and R21/Matrix-MTM
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 327 participants
- Where
- 3 sitesMali
- Study dates
- 19 Aug 2024to 27 Jun 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 12 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age ≥1 to ≤12 months at enrollment.
- Born at ≥37 weeks gestation.
- Parent and/or guardian able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- In good general health and without clinically significant medical history.
- Parent and/or guardian able to provide informed consent.
- Willing to have blood samples and data stored for future research.
- Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study.
Who cannot join
- Body weight <3.5 kg.
- Behavioral, cognitive, or psychiatric disease in the parent and/or guardian that in the opinion of the investigator affects the ability of the parent and/or guardian to understand and comply with the study protocol.
- Any fever (≥ 37.5°C, regardless of route) or acute illness within 7 days prior to randomization.
- Clinically significant congenital anomaly or documented or suspected serious medical illness (e.g., history of epilepsy), serious congenital anomaly, or immediate life-threatening condition in the infant that may interfere with the ability to complete study requirements, as judged by the examining clinician.
- Prior history of a suspected or actual acute life-threatening event.
- Receipt of any blood products, monoclonal or polyclonal antibody/immunoglobulin (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study.
Show all 25Show fewer
- Any acute or chronic illnesses known in the mother during her pregnancy.
- Parental study comprehension examination score of <80% correct or per investigator discretion.
- Hemoglobin, white blood cell (WBC), absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
- Alanine aminotransferase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
- Mother and/or infant infected with HIV.
- Sickle cell disease by testing. (Note: Known sickle cell trait is NOT exclusionary.)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies.
- Receipt of any investigational product within the past 30 days.
- Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. (Note: Past, current, or planned participation in observational studies is NOT exclusionary.)
- History of a severe allergic reaction or anaphylaxis.
- Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors).
- Pre-existing autoimmune or antibody-mediated diseases including but not limited to systemic lupus erythematosus or autoimmune thrombocytopenia.
- Known immunodeficiency syndrome.
- Known asplenia or functional asplenia.
- Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0.
- Previous receipt of the R21/Matrix-MTM vaccine.
- Previous receipt of an investigational malaria vaccine or monoclonal antibody.
- Clinical signs of malnutrition.
- Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of an individual participating in the trial, interfere with the evaluation of the study objectives, or render the participant unable to comply with the protocol.
Trial locations and contacts
3 sites in 1 country.
Mali3 sites
Faladje MRTC Clinic
Faladié, Koulikoro
Kalifabougou MRTC Clinic
Kalifabougou, Koulikoro
Torodo MRTC Clinic
Torodo, Koulikoro
About this study
Official title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Trial 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
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.
Read the detailed description
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.
- Conditions
- Malaria
- Being tested
- L9LS, Placebo, R21/Matrix-MTM
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L9LSBiological
Administered intramuscularly one time.
PlaceboOther
Normal Saline administered intramuscularly one time.
R21/Matrix-MTMBiological
Administered intramuscularly as three total doses given four weeks apart on days 140, 168, 196.
| Study group | Role | What they receive |
|---|---|---|
| Infants 1-4 months: L9LS 150 mg | Experimental | 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. Receives: Biological: L9LS; Biological: R21/Matrix-MTM |
| Infants 5-8 months: L9LS 150 mg | Experimental | 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. Receives: Biological: L9LS; Biological: R21/Matrix-MTM |
| Infants 9-12 months: L9LS 150 mg | Experimental | 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. Receives: Biological: L9LS; Biological: R21/Matrix-MTM |
| Infants 1-4 months: Placebo | Placebo comparator | 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. Receives: Other: Placebo; Biological: R21/Matrix-MTM |
| Infants 5-8 months: Placebo | Placebo comparator | 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. Receives: Other: Placebo; Biological: R21/Matrix-MTM |
| Infants 9-12 months: Placebo | Placebo comparator | 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. Receives: Other: Placebo; Biological: R21/Matrix-MTM |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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
Measured: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)
Secondary outcomes (10)
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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Baseline (enrollment), days 28, 224, and 280
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2024
- Study start19 Aug 2024
- Primary completion27 Jun 2025
- Study completion27 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 327 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institutes of Health (NIH), University of Washington, Harvard School of Public Health (HSPH), Indiana University
- Responsible party
- Sponsor
- Investigators
- Peter Crompton, MD, MPH, Principal investigator, National Institutes of Health (NIH)Kassoum Kayentao, MD, MPH, PhD, Principal investigator, Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06461026
- Sponsor's protocol ID
- 2024/158/CE/USTTB
- Status last verified
- Sep 2026
- First submitted
- 11 Jun 2024
- Last updated
- 1 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Trial 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
- ClinicalTrials.gov ID
- NCT06461026
- Acronym / sponsor ID
- 2024/158/CE/USTTB
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 327 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institutes of Health (NIH), University of Washington, Harvard School of Public Health (HSPH), Indiana University
- Study start
- 19 Aug 2024 (actual)
- Primary completion
- 27 Jun 2025 (actual)
- Study completion
- 27 Jun 2025 (actual)
- First posted
- 14 Jun 2024 (actual)
- Results
- Posted 3 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Infants 1-4 months: L9LS 150 mg | Experimental | Biological: L9LS, Biological: R21/Matrix-MTMInfants 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. |
| Infants 5-8 months: L9LS 150 mg | Experimental | Biological: L9LS, Biological: R21/Matrix-MTMInfants 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. |
| Infants 9-12 months: L9LS 150 mg | Experimental | Biological: L9LS, Biological: R21/Matrix-MTMInfants 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. |
| Infants 1-4 months: Placebo | Placebo comparator | Other: Placebo, Biological: R21/Matrix-MTMInfants 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. |
| Infants 5-8 months: Placebo | Placebo comparator | Other: Placebo, Biological: R21/Matrix-MTMInfants 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. |
| Infants 9-12 months: Placebo | Placebo comparator | Other: Placebo, Biological: R21/Matrix-MTMInfants 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. |
Who may qualify
- Ages
- 1 month to 12 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Age ≥1 to ≤12 months at enrollment.
- Born at ≥37 weeks gestation.
- Parent and/or guardian able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- In good general health and without clinically significant medical history.
- Parent and/or guardian able to provide informed consent.
Key exclusion criteria (25 listed)
- Body weight <3.5 kg.
- Behavioral, cognitive, or psychiatric disease in the parent and/or guardian that in the opinion of the investigator affects the ability of the parent and/or guardian to understand and comply with the study protocol.
- Any fever (≥ 37.5°C, regardless of route) or acute illness within 7 days prior to randomization.
- Clinically significant congenital anomaly or documented or suspected serious medical illness (e.g., history of epilepsy), serious congenital anomaly, or immediate life-threatening condition in the infant that may interfere with the ability to complete study requirements, as judged by the examining clinician.
- Prior history of a suspected or actual acute life-threatening event.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L9LSAdministered intramuscularly one time. | Biological | Infants 1-4 months: L9LS 150 mg, Infants 5-8 months: L9LS 150 mg, Infants 9-12 months: L9LS 150 mg |
| PlaceboNormal Saline administered intramuscularly one time. | Other | Infants 1-4 months: Placebo, Infants 5-8 months: Placebo, Infants 9-12 months: Placebo |
| R21/Matrix-MTMAdministered intramuscularly as three total doses given four weeks apart on days 140, 168, 196. | Biological | Infants 1-4 months: L9LS 150 mg, Infants 1-4 months: Placebo, Infants 5-8 months: L9LS 150 mg, Infants 5-8 months: Placebo, Infants 9-12 months: L9LS 150 mg, Infants 9-12 months: Placebo |
Primary outcome
Participants With Local Adverse Events (AEs)
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 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.
Severity of Local Adverse Events (AEs)
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 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 With Systemic Adverse Events (AEs)
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 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.
Severity of Systemic Adverse Events (AEs)
Time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 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
10 secondary outcomes
Participants With Adverse Events of Special Interest (AESIs) Related to R21/Matrix-MTM Vaccine
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)
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
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
Time frame: Days 0 to 280
Time to Maximum Plasma Concentration (TMax) for L9LS
Time frame: Days 0 to 280
Area Under the Curve (AUC) for L9LS From Day 0 to 168 (AUC_168)
Time frame: Days 0 to 280
Area Under the Curve (AUC) From Day 0 to Last Observed for L9LS
Time frame: Days 0 to 280
Area Under the Concentration Time Curve (AUC) From Day 0 to Infinity
Time frame: Days 0 to 280
Terminal Half-life (t½) of L9LS
Time frame: Days 0 to 280
Participants With Detectable Anti-drug Antibody (ADA) in Sera
Time frame: Baseline (enrollment), days 28, 224, and 280
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Crompton, MD, MPH principal investigator
National Institutes of Health (NIH)
Kassoum Kayentao, MD, MPH, PhD principal investigator
Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing L9LS and R21/Matrix-MTM in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With Local Adverse Events (AEs) (time frame: Within 7 days after administration of L9LS or matching Placebo intervention (administered on Day 0)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.