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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04329104
Other study ID # 2020/32/CE/FMOS/FAPH
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date February 15, 2021
Est. completion date July 5, 2023

Study information

Verified date April 2024
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


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Study Design


Related Conditions & MeSH terms


Intervention

Biological:
VRC-MALMAB0100-00-AB (CIS43LS)
Administered via one-time IV infusion
Other:
Normal saline
Administered via one-time IV infusion

Locations

Country Name City State
Mali Kalifabougou MRTC Clinic Kalifabougou Région De Koulikoro
Mali Torodo MRTC Clinic Torodo Région De Koulikoro

Sponsors (4)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) Harvard School of Public Health (HSPH), Malaria Research and Training Center, Bamako, Mali, University of Washington

Country where clinical trial is conducted

Mali, 

References & Publications (1)

Kayentao K, Ongoiba A, Preston AC, Healy SA, Doumbo S, Doumtabe D, Traore A, Traore H, Djiguiba A, Li S, Peterson ME, Telscher S, Idris AH, Kisalu NK, Carlton K, Serebryannyy L, Narpala S, McDermott AB, Gaudinski M, Traore S, Cisse H, Keita M, Skinner J, — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Within 7 days after administration of CIS43LS
Primary 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
Within 7 days after the administration of CIS43LS
Primary 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. Within 7 days after the administration of CIS43LS
Primary 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
Within 7 days after the administration of CIS43LS
Secondary Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination The incidence of 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. Day 7 through week 24 (168 days) after administration of intervention
Secondary Participants With Plasmodium Falciparum (Pf) Infection Detected by RT-PCR The occurrence of 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 7 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. Day 7 through week 24 (168 days)
Secondary Dose Escalation Study: Measurement of CIS43LS in Sera of Recipients Measurement of CIS43LS in Sera of Recipients - Dose Escalation Study Concentrations of CIS43LS will be measured by a Meso Scale Discovery LLC-based automation platform. The concentration at the visit prior to the first Plasmodium Falciparum (Pf) infection will be used to assess CIS43LS-mediated protection. Concentrations of CIS43LS in blood will help assess durability of CIS43LS at each dose level and will allow for correlation with Pf infection risk. Measured through Week 24
Secondary Efficacy Study: Measurement of CIS43LS in Sera of Recipients Efficacy Study only Concentrations of CIS43LS will be measured by a Meso Scale Discovery LLC-based automation platform. The concentration at the visit prior to the first Pf infection will be used to assess CIS43LS-mediated protection. Concentrations of CIS43LS in blood will Measured through Week 24
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