Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05304611 | Anti-malaria MAb in Malian Children | PHASE2 | COMPLETED | 365 | — | — | Mar 18, 2022 | Apr 20, 2024 | Jul 10, 2025 | 2 | Mali |
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.
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
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.
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
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.
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.
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.
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.
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.
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
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.
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
| Arm | Type | Description |
|---|---|---|
| Adult Dose-escalation study: Arm 1: 300 mg of L9LS | EXPERIMENTAL | Adult 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 | EXPERIMENTAL | Adult 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 | EXPERIMENTAL | Adult 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 | EXPERIMENTAL | Pediatric 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 | EXPERIMENTAL | Pediatric 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_COMPARATOR | Pediatric subjects ages 6-10 receive single dose placebo of normal saline subcutaneously for comparison. |
| Pediatric Efficacy study: Arm 1: 150 mg of L9LS | EXPERIMENTAL | Pediatric subjects ages 6-10 receive single dose of 150 mg L9LS subcutaneously. |
| Pediatric Efficacy study: Arm 2: 300 mg of L9LS | EXPERIMENTAL | Pediatric subjects ages 6-10 receive single dose of 300 mg L9LS subcutaneously. |
| Pediatric Efficacy study: Arm 3: Placebo | PLACEBO_COMPARATOR | Pediatric subjects ages 6-10 receive single dose placebo of normal saline subcutaneously. |
| Pediatric Extension study: Arm 1: 150 mg of L9LS | EXPERIMENTAL | Pediatric 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 | EXPERIMENTAL | Pediatric 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_COMPARATOR | Pediatric 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. |
| Name | Type | Description |
|---|---|---|
| L9LS (VRC-MALMAB0114-00-AB) Subcutaneous injection | BIOLOGICAL | Administered one time via subcutaneous route. |
| L9LS (VRC-MALMAB0114-00-AB) intravenous injection | BIOLOGICAL | Administered one time via intravenous route. |
| Placebo | OTHER | Normal saline administered one time via subcutaneous route. |
Inclusion Criteria: * Is within the appropriate age range for the respective cohort: 1. Children: Aged ≥6 years and \<11 years. 2. 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 ...