Anti-malaria MAb in Malian Children
L9LS
Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Dose-Escalation Trial in Adults and Children and a Randomized, Double-Blind Trial of Children in Mali
1 other identifier
interventional
365
1 country
2
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of onetime subcutaneous (SC) or intravenous (IV) administration of monoclonal antibody (MAb) L9LS in healthy Malian adults and one-time SC administration of L9LS in healthy Malian children, as well as its protective efficacy against naturally occurring Plasmodium falciparum (Pf) infection over a 7-month malaria season in healthy Malian children 6-10 years of age.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2022
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2022
CompletedStudy Start
First participant enrolled
March 18, 2022
CompletedFirst Posted
Study publicly available on registry
March 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 20, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 20, 2024
CompletedResults Posted
Study results publicly available
July 10, 2024
CompletedJuly 10, 2025
June 1, 2025
2.1 years
February 28, 2022
June 12, 2024
June 23, 2025
Conditions
Outcome Measures
Primary Outcomes (12)
Participants With Local Adverse Events (AEs) - Year One
Number of participants with local adverse events occurring within 7 days after administration of L9LS. 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.
Within 7 days after administration of L9LS
Severity of Local Adverse Events (AEs) - Year One
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
Within 7 days after administration of L9LS
Participants With Systemic Adverse Events (AEs) - Year One
Number of participants with local adverse events occurring within 7 days after administration of L9LS. 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.
Within 7 days after the administration of L9LS
Severity of Systemic Adverse Events (AEs) - Year One
The severity of systemic AEs occurring after the administration of L9LS 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
Within 7 days after the administration of L9LS
Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination - Efficacy Study
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 from participants from day 14 through week 28 (196 days) after administration of L9LS or placebo. Analysis was done as number of participants who had at least one positive blood smear.
Day 7 through week 28
Participants With Detectable Anti-drug Antibody (ADA) in Sera - Extension Study
Number of participants with detectable anti-drug antibody (ADA) in sera after exposure to L9LS. Serum was collected from participants at specific timepoints throughout the study, on days 0, 7, 28, 84, 168, and 196. 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 through week 36
Maximum Total Plasma Concentration (Cmax) for L9LS - Extension Study
Maximum total plasma concentration (Cmax) following a dose of 150 mg or 300 mg L9LS. Serum collected on days 0, 7, 28, 84, 140, 196, \& 252 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 observed maximum concentration based on all available timepoints and cumulative output was calculated as the central tendency and dispersion metric based on the observed maximum concentrations.
Measured through Week 36
Time to Maximum Plasma Concentration (TMax) for L9LS - Extension Study
Time to maximum total plasma concentration (Cmax) following a dose of 150 mg or 300 mg L9LS. Serum collected on days 0, 7, 28, 84, 140, 196, \& 252 after the 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 through Week 36
Participants With Local Adverse Events (AEs) - Extension Study
Number of participants with local adverse events occurring within 7 days after administration of L9LS. 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.
Within 7 days after administration of L9LS
Severity of Local Adverse Events (AEs) - Extension Study
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
Within 7 days after administration of L9LS
Participants With Systemic Adverse Events (AEs) - Extension Study
Number of participants with local adverse events occurring within 7 days after administration of L9LS. 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.
Within 7 days after the administration of L9LS
Severity of Systemic Adverse Events (AEs) - Extension Study
The severity of systemic AEs occurring after the administration of L9LS 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
Within 7 days after the administration of L9LS
Secondary Outcomes (7)
Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR)
Measured through week 24 (dose escalation study) and week 28 (efficacy study)
Participants With Clinical Malaria - Pediatric Dose Escalation Study
Measured through Week 28
Participants With Clinical Malaria - Pediatric Efficacy Study
Measured through Week 28
Participants With Clinical Malaria Detected by Microscopic Examination of Thick Blood Smear - Pediatric Dose Escalation Study
Measured through Week 28
Participants With Clinical Malaria Detected by Microscopic Examination of Thick Blood Smear - Pediatric Efficacy Study
Measured through Week 24
- +2 more secondary outcomes
Study Arms (12)
Adult Dose-escalation study: Arm 1: 300 mg of L9LS
EXPERIMENTALAdult participants receive single dose of 300 mg of L9LS subcutaneously. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2.
Adult Dose-escalation study: Arm 2: 600 mg of L9LS
EXPERIMENTALAdult participants receive single dose of 600 mg of L9LS subcutaneously. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3.
Adult Dose-escalation study: Arm 3: 20 mg/kg of L9LS
EXPERIMENTALAdult participants receive highest single dose of 20 mg/kg IV of L9LS intravenously. Once subjects reach day 7 post-administration without safety concerns dosing begins for pediatric subjects dose escalation arm 1.
Pediatric Dose-escalation study: Arm 1: 150 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 years receive single dose of 150 mg L9LS subcutaneously. Once subjects reach day 7 post-administration without safety concerns, dosing begins for arm 2.
Pediatric Dose-escalation study: Arm 2: 300 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 years receive single dose of 300 mg L9LS subcutaneously. Once subjects reach day 7 post-administration without safety concerns, dosing begins for the pediatric efficacy study arms.
Pediatric Dose-escalation study: Arm 3: Placebo
PLACEBO COMPARATORPediatric subjects ages 6-10 receive single dose placebo of normal saline subcutaneously for comparison.
Pediatric Efficacy study: Arm 1: 150 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 receive single dose of 150 mg L9LS subcutaneously.
Pediatric Efficacy study: Arm 2: 300 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 receive single dose of 300 mg L9LS subcutaneously.
Pediatric Efficacy study: Arm 3: Placebo
PLACEBO COMPARATORPediatric subjects ages 6-10 receive single dose placebo of normal saline subcutaneously.
Pediatric Extension study: Arm 1: 150 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 who completed year one of the study and agreed to continue with the extension were randomized to receive 150 mg of L9LS subcutaneously.
Pediatric Extension study: Arm 2: 300 mg of L9LS
EXPERIMENTALPediatric subjects ages 6-10 who completed year one of the study and agreed to continue with the extension were randomized to receive 300 mg of L9LS subcutaneously.
Pediatric Extension study: Arm 3: Placebo
PLACEBO COMPARATORPediatric subjects ages 6-10 who completed year one of the study and agreed to continue with the extension were randomized to receive placebo of normal saline subcutaneously.
Interventions
Administered one time via subcutaneous route.
Administered one time via intravenous route.
Normal saline administered one time via subcutaneous route.
Eligibility Criteria
You may qualify if:
- Is within the appropriate age range for the respective cohort:
- Children: Aged ≥6 years and \<11 years.
- Adults: Aged ≥18 years.
- 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.
- Adult participants or parent and/or guardian of minor participants able to provide informed consent.
- Willing to have blood samples and data stored for future research.
- Resides in or near Kalifabougou or Torodo, Mali, and available for the duration of the study.
- For the adult cohort, females of childbearing potential must be willing to use reliable contraception from 21 days prior to study day 0 through the final study visit as described below.
- Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device.
- Nonchildbearing women will be required to report date of last menstrual period, history of surgical sterility (i.e., tubal ligation, hysterectomy) or premature ovarian insufficiency, and will have urine or serum pregnancy test performed per protocol.
- Participated in the first year of the protocol.
- 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.
- +2 more criteria
You may not qualify if:
- Body weight \<15 kg or \>30 kg for children, or \>60 kg for adults.
- Currently receiving or planning to receive seasonal malaria chemoprevention (SMC).
- Any history of menses (for 6-10 year old cohort) or positive pregnancy test at screening (for adult cohort).
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol.
- Subject (for adult subjects) or parental (for minor subjects) study comprehension examination score of \<80% correct or per investigator discretion.
- Hemoglobin, white blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.)
- Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.)
- Infected with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
- Clinically significant abnormal electrocardiogram (ECG; Corrected QT Interval (QTc) \>460 or other significant abnormal findings, including unexplained tachycardia or bradycardia).
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- Receipt of any investigational product within the past 30 days.
- Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- History of a severe allergic reaction or anaphylaxis.
- Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years).
- Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors).
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)lead
- National Institutes of Health (NIH)collaborator
- Malaria Research and Training Center, Bamako, Malicollaborator
- University of the Sciences, Techniques and Technologies of Bamakocollaborator
- University of Washingtoncollaborator
- Harvard School of Public Health (HSPH)collaborator
- Indiana University School of Medicinecollaborator
Study Sites (2)
Kalifabougou MRTC Clinic
Kalifabougou, Koulikoro, Mali
Torodo MRTC Clinic
Torodo, Koulikoro, Mali
Related Publications (1)
Kayentao K, Ongoiba A, Preston AC, Healy SA, Hu Z, Skinner J, Doumbo S, Wang J, Cisse H, Doumtabe D, Traore A, Traore H, Djiguiba A, Li S, Peterson ME, Telscher S, Idris AH, Adams WC, McDermott AB, Narpala S, Lin BC, Serebryannyy L, Hickman SP, McDougal AJ, Vazquez S, Reiber M, Stein JA, Gall JG, Carlton K, Schwabl P, Traore S, Keita M, Zeguime A, Ouattara A, Doucoure M, Dolo A, Murphy SC, Neafsey DE, Portugal S, Djimde A, Traore B, Seder RA, Crompton PD; Mali Malaria mAb Trial Team. Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria. N Engl J Med. 2024 May 2;390(17):1549-1559. doi: 10.1056/NEJMoa2312775. Epub 2024 Apr 26.
PMID: 38669354RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Peter Crompton
- Organization
- National Institute of Allergy and Infectious Diseases (NIAID)
Study Officials
- PRINCIPAL INVESTIGATOR
Kassoum Kayentao, MD, MPH, PhD
Faculté de Médecine Pharmacie d'Odontostomatologie (FMPOS)
- PRINCIPAL INVESTIGATOR
Peter Crompton, MD, MPH
National Institutes of Health (NIH)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2022
First Posted
March 31, 2022
Study Start
March 18, 2022
Primary Completion
April 20, 2024
Study Completion
April 20, 2024
Last Updated
July 10, 2025
Results First Posted
July 10, 2024
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- 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 at NIH
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.