Safety and Efficacy of CIS43LS Anti-malaria mAb in Mali

NCT04329104 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2020/32/CE/FMOS/FAPH
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Plasmodium Falciparum Infection; Malaria

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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.

  Day 7 through week 24 (168 days) after administration of intervention

Secondary Outcomes (3)

• Participants With Plasmodium Falciparum (Pf) Infection Detected by Reverse Transcription Polymerase Chain Reaction (RT-PCR)

  Day 21 through week 24 (168 days) after administration of intervention

• Maximum Serum Concentration (Cmax) for CIS43LS

  Measured through Week 24

• Time to Maximum Serum Concentration (Tmax) for CIS43LS

  One to 24 hours post-infusion

Study Arms (6)

Dose-escalation study: Arm 1: 5 mg/kg of CIS43LS

EXPERIMENTAL

Participants receive 5 mg/kg of CIS43LS as one time intravenous infusion on Day 0.

Biological: VRC-MALMAB0100-00-AB (CIS43LS)

Dose-escalation study: Arm 2: 10 mg/kg of CIS43LS

EXPERIMENTAL

Participants receive 10 mg/kg of CIS43LS as one time intravenous infusion on Day 0.

Biological: VRC-MALMAB0100-00-AB (CIS43LS)

Dose-escalation study: Arm 3: 40 mg/kg of CIS43LS

EXPERIMENTAL

Participants receive 40 mg/kg of CIS43LS as one time intravenous infusion on Day 0.

Biological: VRC-MALMAB0100-00-AB (CIS43LS)

Efficacy study: Arm 1: 10 mg/kg of CIS43LS

EXPERIMENTAL

Participants receive 10 mg/kg of CIS43LS as one time intravenous infusion on Day 0.

Biological: VRC-MALMAB0100-00-AB (CIS43LS)

Efficacy study: Arm 2: 40 mg/kg of CIS43LS

EXPERIMENTAL

Participants receive 40 mg/kg of CIS43LS as one time intravenous infusion on Day 0.

Biological: VRC-MALMAB0100-00-AB (CIS43LS)

Efficacy study: Arm 3: Placebo

PLACEBO COMPARATOR

Participants receive placebo as one time intravenous infusion on Day 0.

Other: Normal saline

Interventions

VRC-MALMAB0100-00-AB (CIS43LS) BIOLOGICAL

Administered via one-time intravenous infusion

Dose-escalation study: Arm 1: 5 mg/kg of CIS43LS; Dose-escalation study: Arm 2: 10 mg/kg of CIS43LS; Dose-escalation study: Arm 3: 40 mg/kg of CIS43LS; Efficacy study: Arm 1: 10 mg/kg of CIS43LS; Efficacy study: Arm 2: 40 mg/kg of CIS43LS

Normal saline OTHER

Administered via one-time intravenous infusion

Efficacy study: Arm 3: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged ≥18 and ≤55 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.
• 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.
• 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.

You may not qualify if:

• Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β-hCG) test (if female).
• Currently breastfeeding.
• 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.
• 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 human immunodeficiency virus (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).
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.
• Known immunodeficiency syndrome.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• University of Washington: collaborator
• Harvard School of Public Health (HSPH): collaborator

Study Sites (2)

Kalifabougou MRTC Clinic

Kalifabougou, Koulikoro, Mali

Location

Torodo MRTC Clinic

Torodo, Koulikoro, Mali

Location

Related Publications (2)

• 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, Hu Z, Zeguime A, Ouattara A, Doucoure M, Dolo A, Djimde A, Traore B, Seder RA, Crompton PD; Mali Malaria mAb Trial Team. Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali. N Engl J Med. 2022 Nov 17;387(20):1833-1842. doi: 10.1056/NEJMoa2206966. Epub 2022 Oct 31.

  PMID: 36317783 RESULT

• Skinner J, Kayentao K, Ongoiba A, Healy SA, Hu Z, Preston AC, Niangaly A, Schwabl P, Cisse H, Doumbo S, Doumtabe D, Traore A, Li S, Peterson ME, Seilie AM, Chavtur C, Staubus W, Chang M, Kelley K, Traore H, Djiguiba A, Keita M, Ouattara A, Doucoure M, Keita M, Diarra D, Sylla M, Diakite D, Konate M, Traore S, Zeguime A, Dolo A, Neafsey DE, Murphy SC, Traore B, Seder RA, Crompton PD. Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial. Nat Med. 2025 Aug;31(8):2682-2690. doi: 10.1038/s41591-025-03739-y. Epub 2025 Jun 3.

  PMID: 40461818 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

CIS43LS; Saline Solution

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Peter Crompton
• Organization: National Institute of Allergy and Infectious Diseases (NIAID)

pcrompton@niaid.nih.gov

301-761-5042

Study Officials

• Kassoum Kayentao, MD, MPH, PhD

  Faculté de Médecine Pharmacie d'Odontostomatologie (FMPOS)

  PRINCIPAL INVESTIGATOR

• Peter D. Crompton, MD, MPH

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: February 15, 2021
• Primary Completion: January 26, 2022
• Study Completion: July 5, 2023
• Last Updated: April 9, 2025
• Results First Posted: May 2, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

MA (2)