The purpose of this study is to evaluate the safety, tolerability, and efficacy of VRC MALMAB0100-00-AB (CIS43LS), a human monoclonal antibody, against naturally occurring Plasmodium falciparum (Pf) infection.
This study will evaluate the safety, tolerability, and efficacy of VRC MALMAB0100-00-AB (CIS43LS), a human monoclonal antibody, against naturally occurring Plasmodium falciparum (Pf) infection. The first part of the study is an open-label dose-escalation study for safety and tolerability. Participants will be assigned to one of three dose arms. Dosing will begin in the lowest dose arm. Once all participants in that arm reach Day 7 post-infusion, if no safety concerns have arisen, dosing will begin at the subsequent dose level. This process will be repeated until participants complete the third dose arm. Participants will be followed for safety to assess adverse events (AEs) at study visits 1, 3, 7, 14, 21, and 28 days after administration, then monthly through 24 weeks after administration. After the last subject in the highest dose arm reaches Day 7 safety follow-up, an interim safety evaluation will be performed before enrollment begins for the second part of the study. The second part of the study is a randomized, double-blind, placebo-controlled trial to assess safety and protective efficacy of CIS43LS and placebo. Participants in the efficacy study will receive the study agent and be followed at study visits 1, 3, 7, 14, 21, and 28 days later, and once every 2 weeks thereafter through 24 weeks. Primary study assessments include physical examinations and blood collection for identification of Pf infection and other research laboratory evaluations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
348
Administered via one-time intravenous infusion
Administered via one-time intravenous infusion
Kalifabougou MRTC Clinic
Kalifabougou, Koulikoro, Mali
Torodo MRTC Clinic
Torodo, Koulikoro, Mali
Participants With Local Adverse Events (AEs)
Participants with incidence of local adverse events occurring within 7 days after administration of CIS43LS. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion.
Time frame: Within 7 days after administration of CIS43LS
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 the administration of CIS43LS
Participants With Systemic Adverse Events (AEs)
Participants with incidence of systemic adverse events occurring within 7 days after product administration of CIS43LS. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain.
Time frame: Within 7 days after the administration of CIS43LS
Severity of Systemic Adverse Events (AEs)
The severity of systemic AEs occurring after the administration of CIS43LS 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
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Time frame: Within 7 days after the administration of CIS43LS
Participants With Plasmodium Falciparum (Pf) Infection 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 from participants from day 7 through week 24 (168 days) after administration of CIS43LS or placebo. Sample was collected every two weeks until week 24.
Time frame: Day 7 through week 24 (168 days) after administration of intervention
Participants With Plasmodium Falciparum (Pf) Infection Detected by Reverse Transcription Polymerase Chain Reaction (RT-PCR)
Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by reverse transcription polymerase chain reaction (RT-PCR) using dried blood spot specimen collected from participants from day 21 through week 24 (168 days) after administration of CIS43LS or placebo. Sample was collected every two weeks until 24 weeks. Plasmodium 18S rRNA RT-PCR assay was applied to dried blood spots during analysis.
Time frame: Day 21 through week 24 (168 days) after administration of intervention
Maximum Serum Concentration (Cmax) for CIS43LS
Maximum serum concentration (Cmax) of CIS43LS by dose group following a single intravenous administration to assess durability of CIS43LS and allow for correlation with Plasmodium falciparum (Pf) infection risk. Cmax is the peak serum concentration that CIS43LS achieves after it has been administered. It is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group and measured by a Meso Scale Discovery LLC-based automation platform.
Time frame: Measured through Week 24
Time to Maximum Serum Concentration (Tmax) for CIS43LS
Time to maximum total serum concentration (Cmax) of CIS43LS by dose group following a single intravenous administration. Tmax is the time it takes to reach Cmax of CIS43LS after it has been administered; it is determined based on the summary PK curve for each dose group. This was calculated by subtracting the time the CIS43LS intravenous infusion was stopped from the time the blood was collected for the Cmax, at the post-one hour blood draw.
Time frame: One to 24 hours post-infusion