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Plasmodium Falciparum InfectionPhase 2NCT04329104

Safety and Efficacy of CIS43LS Anti-malaria mAb in Mali

A Phase 2 study testing VRC-MALMAB0100-00-AB (CIS43LS) and Normal saline in people with Plasmodium Falciparum Infection and Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in Mali.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Plasmodium Falciparum Infection, Malaria
What is being tested?
VRC-MALMAB0100-00-AB (CIS43LS) and Normal saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
348 participants
Where
2 sitesMali
Study dates
15 Feb 2021to 5 Jul 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.)
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  • Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
  • Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.)
  • 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.
  • Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. (Note: Past, current, or planned participation in observational studies is NOT exclusionary.)
  • 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.
  • Known asplenia or functional asplenia.
  • Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0.
  • Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration.
  • Receipt of immunoglobulins and/or blood products within the past 6 months.
  • Previous receipt of an investigational malaria vaccine in the last 5 years.
  • Known allergies or contraindication against artemether-lumefantrine.
  • Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol.

Trial locations and contacts

2 sites in 1 country.

Mali2 sites

  • Kalifabougou MRTC Clinic

    Kalifabougou, Koulikoro

  • Torodo MRTC Clinic

    Torodo, Koulikoro

Other trials in Mali

About this study

Official title: Safety and Efficacy of VRC-MALMAB0100-00-AB (CIS43LS), a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Dose-Escalation Trial and a Randomized, Double-Blind Trial of Adults in Mali

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.

Read the detailed 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.

Being tested
VRC-MALMAB0100-00-AB (CIS43LS), Normal saline
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Administered via one-time intravenous infusion

  • Normal salineOther

    Administered via one-time intravenous infusion

Study groups in NCT04329104
Study groupRoleWhat they receive
Dose-escalation study: Arm 1: 5 mg/kg of CIS43LSExperimentalParticipants receive 5 mg/kg of CIS43LS as one time intravenous infusion on Day 0.
Receives: Biological: VRC-MALMAB0100-00-AB (CIS43LS)
Dose-escalation study: Arm 2: 10 mg/kg of CIS43LSExperimentalParticipants receive 10 mg/kg of CIS43LS as one time intravenous infusion on Day 0.
Receives: Biological: VRC-MALMAB0100-00-AB (CIS43LS)
Dose-escalation study: Arm 3: 40 mg/kg of CIS43LSExperimentalParticipants receive 40 mg/kg of CIS43LS as one time intravenous infusion on Day 0.
Receives: Biological: VRC-MALMAB0100-00-AB (CIS43LS)
Efficacy study: Arm 1: 10 mg/kg of CIS43LSExperimentalParticipants receive 10 mg/kg of CIS43LS as one time intravenous infusion on Day 0.
Receives: Biological: VRC-MALMAB0100-00-AB (CIS43LS)
Efficacy study: Arm 2: 40 mg/kg of CIS43LSExperimentalParticipants receive 40 mg/kg of CIS43LS as one time intravenous infusion on Day 0.
Receives: Biological: VRC-MALMAB0100-00-AB (CIS43LS)
Efficacy study: Arm 3: PlaceboPlacebo comparatorParticipants receive placebo as one time intravenous infusion on Day 0.
Receives: Other: Normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Within 7 days after administration of CIS43LS

  2. 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

    Measured: Within 7 days after the administration of CIS43LS

  3. 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.

    Measured: Within 7 days after the administration of CIS43LS

  4. 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

    Measured: Within 7 days after the administration of CIS43LS

  5. 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.

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

Secondary outcomes (3)

  1. 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.

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

  2. 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.

    Measured: Measured through Week 24

  3. 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.

    Measured: One to 24 hours post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2020
  2. Study start15 Feb 2021
  3. Primary completion26 Jan 2022
  4. Study completion5 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
348 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04329104
Sponsor's protocol ID
2020/32/CE/FMOS/FAPH
Status last verified
Mar 2025
First submitted
30 Mar 2020
Last updated
9 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36317783

  • Tran TM, Hu Z, Kayentao K, Ongoiba A, Jones S, Abla N, Healy SA, Cisse H, Chang BH, Skinner J, Serebryannyy L, Narpala SR, Schlesinger R, Low KH, Kazmierski R, Lin BC, Dias J, Doumbo S, Doumtabe D, Preston AC, Li S, Peterson ME, Oberai A, Shandling AD, Campo JJ, Murphy SC, Telscher S, Coates EE, Capparelli EV, Dolo A, Traore B, Seder RA, Crompton PD. Pharmacokinetics and pharmacodynamics of a long-acting monoclonal antibody against malaria in African adults. J Clin Invest. 2026 Jul 2:e207559. doi: 10.1172/JCI207559. Online ahead of print.

    PubMed 42407014

  • 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.

    PubMed 40461818

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VRC-MALMAB0100-00-AB (CIS43LS) and Normal saline in people with Plasmodium Falciparum Infection and Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in Mali.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants With Local Adverse Events (AEs) (time frame: Within 7 days after administration of CIS43LS). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04329104, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.

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