Ignite Creation Date:
2025-12-24 @ 9:48 PM
Ignite Modification Date:
2025-12-25 @ 7:26 PM
Study NCT ID:
NCT04206332
Status:
COMPLETED
Last Update Posted:
2023-04-18
First Post:
2019-12-19
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Trial to Evaluate CIS43LS in Healthy Adults
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
Study Overview
Official Title:
A Phase 1, Dose Escalation, Open-Label Clinical Trial With Experimental Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Protective Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0100-00-AB (CIS43LS), in Healthy, Malaria-Naive Adults
Status:
COMPLETED
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
People get malaria when they are bitten by an infected mosquito. Malaria can be serious and sometimes deadly. Although there are medicines to treat malaria, there is no vaccine that fully prevents infection. Researchers want to test if an experimental drug can help.
Objective:
To test the safety and effectiveness of a drug called CIS43LS that could prevent malaria infection.
Eligibility:
Healthy people ages 18-50 who have never been infected with malaria
Design:
Participants were enrolled on the basis of eligibility criteria, evaluated by clinical laboratory tests, self-reported medical history, and physical examination.
Participants received CIS43LS either infused into a vein in their arm or injected into the fat under the skin. They were monitored for side effects for up to 4 hours after they received the drug. Participants received a thermometer and recorded their temperature and symptoms every day on/with/via a diary card for 7 days after administration. The administration site was checked for redness, swelling, itching or bruising.
Participants had up to 12 follow-up visits. At follow-up visits, participants had blood drawn and were checked for health changes or problems.
Most participants who received CIS43LS took part in a Controlled Human Malaria Infection Challenge (CHMI) along with control participants who did not receive CIS43LS. During the CHMI, mosquitoes carrying the malaria parasite bit participants in a controlled setting. The participants had clinic visits every day for up to 12 days starting 7 days after the CHMI. Participants were treated right away with antimalarial medication if they tested positive for malaria. Approximately 21 days after the CHMI, participants were treated with antimalarial medication for 3 days.
The study lasted 2-6 months depending on the participant's study group.
People get malaria when they are bitten by an infected mosquito. Malaria can be serious and sometimes deadly. Although there are medicines to treat malaria, there is no vaccine that fully prevents infection. Researchers want to test if an experimental drug can help.
Objective:
To test the safety and effectiveness of a drug called CIS43LS that could prevent malaria infection.
Eligibility:
Healthy people ages 18-50 who have never been infected with malaria
Design:
Participants were enrolled on the basis of eligibility criteria, evaluated by clinical laboratory tests, self-reported medical history, and physical examination.
Participants received CIS43LS either infused into a vein in their arm or injected into the fat under the skin. They were monitored for side effects for up to 4 hours after they received the drug. Participants received a thermometer and recorded their temperature and symptoms every day on/with/via a diary card for 7 days after administration. The administration site was checked for redness, swelling, itching or bruising.
Participants had up to 12 follow-up visits. At follow-up visits, participants had blood drawn and were checked for health changes or problems.
Most participants who received CIS43LS took part in a Controlled Human Malaria Infection Challenge (CHMI) along with control participants who did not receive CIS43LS. During the CHMI, mosquitoes carrying the malaria parasite bit participants in a controlled setting. The participants had clinic visits every day for up to 12 days starting 7 days after the CHMI. Participants were treated right away with antimalarial medication if they tested positive for malaria. Approximately 21 days after the CHMI, participants were treated with antimalarial medication for 3 days.
The study lasted 2-6 months depending on the participant's study group.
Detailed Description:
This was a multicenter, three-part, first-in-human, Phase 1, open-label, dose escalation study to evaluate the dose, safety, tolerability and protective efficacy of an anti-malaria human monoclonal antibody, VRC-MALMAB0100-00-AB (CIS43LS). The primary objective was to evaluate the safety and tolerability of CIS43LS when administered by either intravenous (IV) or subcutaneous (SC) routes. The secondary objectives were to evaluate the pharmacokinetics of CIS43LS at each dose level, determine if IV or SC administration will confer protection following a controlled human malaria infection (CHMI), and estimate the lowest protective dose of CIS43LS.
Part A: Part A evaluated the doses and routes in an open-label, dose escalation design.
Part B: Part B evaluated CIS43LS doses and routes prior to CHMI in participants previously enrolled in Part A and new Part B enrollees. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS dose intravenously. Additional participants were enrolled in Part B and received CIS43LS intravenously.
Part C: Part C evaluated CIS43LS doses and routes needed to reach a threshold of protection by assessing serum concentration prior to CHMI in a dose down design.
Study Product:
CIS43LS is a human immunoglobulin gamma-1 (IgG1) monoclonal antibody that was developed and manufactured by the National Institutes of Health (NIH) Vaccine Research Center (VRC). A recombinant Chinese hamster ovary DG44 clonal cell line14 developed by the Vaccine Production Program was transferred to the VRC pilot plant for clinical material manufacture. The study product was manufactured according to Good Manufacturing Practice at the VRC pilot plant operated by the Vaccine Clinical Materials Program, Leidos Biomedical Research (Frederick, MD, USA).
VRC-MALMAB0100-00-AB (CIS43LS) is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum (P. falciparum) circumsporozoite protein and incorporates an LS mutation to increase product half-life in plasma.
Participants:
A total of 71 participants enrolled in the study as follows:
Part A: 29 participants enrolled in Groups 1-5
Part B: 21\* participants enrolled in Groups 6-10
\*Out of the 21 Part B participants, 11 were newly enrolled and 10 were Part A participants who re-enrolled.
Of the 10 Part A participants who re-enrolled in Part B, 3 were back up participants who did not receive additional CIS43LS or CHMI and were terminated early because they were not needed.
Therefore, only 18 participants were actively enrolled in Part B: 11 newly enrolled and 7 Part A participants who re-enrolled.
Part C: 31 participants enrolled in Groups 11-16
Of the 71 participants enrolled, 47 participants received at least one dose of CIS43LS and 43 participants completed the CHMI.
Of the 47 participants who received CIS43LS, 4 participants who received a dose in Part A were also enrolled in Part B and received a second dose as follows:
* one participant received a 5 mg/kg IV dose in Part A and 20 mg/kg IV dose in Part B,
* one participant received a 5 mg/kg SC dose in Part A and 20 mg/kg IV dose in Part B, and
* two participants received a 20 mg/kg IV dose in Part A and Part B.
Therefore, a total of 51 doses of CIS43LS were administered to 47 participants as follows:
* 7 doses of 1 mg/kg IV
* 8 doses of 5 mg/kg SC
* 8 doses of 5 mg/kg IV
* 3 doses of 10 mg/kg IV
* 4 doses of 10 mg/kg SC
* 9 doses of 20 mg/kg IV and
* 12 doses of 40 mg/kg IV
Study Duration:
Participants who received CIS43LS were followed for up to 24 weeks after product administration. Control participants were followed through 7 weeks after CHMI.
Part A: Part A evaluated the doses and routes in an open-label, dose escalation design.
Part B: Part B evaluated CIS43LS doses and routes prior to CHMI in participants previously enrolled in Part A and new Part B enrollees. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS dose intravenously. Additional participants were enrolled in Part B and received CIS43LS intravenously.
Part C: Part C evaluated CIS43LS doses and routes needed to reach a threshold of protection by assessing serum concentration prior to CHMI in a dose down design.
Study Product:
CIS43LS is a human immunoglobulin gamma-1 (IgG1) monoclonal antibody that was developed and manufactured by the National Institutes of Health (NIH) Vaccine Research Center (VRC). A recombinant Chinese hamster ovary DG44 clonal cell line14 developed by the Vaccine Production Program was transferred to the VRC pilot plant for clinical material manufacture. The study product was manufactured according to Good Manufacturing Practice at the VRC pilot plant operated by the Vaccine Clinical Materials Program, Leidos Biomedical Research (Frederick, MD, USA).
VRC-MALMAB0100-00-AB (CIS43LS) is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum (P. falciparum) circumsporozoite protein and incorporates an LS mutation to increase product half-life in plasma.
Participants:
A total of 71 participants enrolled in the study as follows:
Part A: 29 participants enrolled in Groups 1-5
Part B: 21\* participants enrolled in Groups 6-10
\*Out of the 21 Part B participants, 11 were newly enrolled and 10 were Part A participants who re-enrolled.
Of the 10 Part A participants who re-enrolled in Part B, 3 were back up participants who did not receive additional CIS43LS or CHMI and were terminated early because they were not needed.
Therefore, only 18 participants were actively enrolled in Part B: 11 newly enrolled and 7 Part A participants who re-enrolled.
Part C: 31 participants enrolled in Groups 11-16
Of the 71 participants enrolled, 47 participants received at least one dose of CIS43LS and 43 participants completed the CHMI.
Of the 47 participants who received CIS43LS, 4 participants who received a dose in Part A were also enrolled in Part B and received a second dose as follows:
* one participant received a 5 mg/kg IV dose in Part A and 20 mg/kg IV dose in Part B,
* one participant received a 5 mg/kg SC dose in Part A and 20 mg/kg IV dose in Part B, and
* two participants received a 20 mg/kg IV dose in Part A and Part B.
Therefore, a total of 51 doses of CIS43LS were administered to 47 participants as follows:
* 7 doses of 1 mg/kg IV
* 8 doses of 5 mg/kg SC
* 8 doses of 5 mg/kg IV
* 3 doses of 10 mg/kg IV
* 4 doses of 10 mg/kg SC
* 9 doses of 20 mg/kg IV and
* 12 doses of 40 mg/kg IV
Study Duration:
Participants who received CIS43LS were followed for up to 24 weeks after product administration. Control participants were followed through 7 weeks after CHMI.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 20-I-0017 | None | None | View |