Ignite Creation Date:
2024-05-06 @ 2:04 PM
Last Modification Date:
2024-10-26 @ 1:24 PM
Study NCT ID:
NCT04206332
Status:
COMPLETED
Last Update Posted:
2023-04-18
First Post:
2019-12-19
Brief Title:
Trial to Evaluate CIS43LS in Healthy Adults
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
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 onwithvia 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 participants 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 onwithvia 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 participants 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 mgkg IV dose in Part A and 20 mgkg IV dose in Part B
one participant received a 5 mgkg SC dose in Part A and 20 mgkg IV dose in Part B and
two participants received a 20 mgkg 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 mgkg IV
8 doses of 5 mgkg SC
8 doses of 5 mgkg IV
3 doses of 10 mgkg IV
4 doses of 10 mgkg SC
9 doses of 20 mgkg IV and
12 doses of 40 mgkg 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 mgkg IV dose in Part A and 20 mgkg IV dose in Part B
one participant received a 5 mgkg SC dose in Part A and 20 mgkg IV dose in Part B and
two participants received a 20 mgkg 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 mgkg IV
8 doses of 5 mgkg SC
8 doses of 5 mgkg IV
3 doses of 10 mgkg IV
4 doses of 10 mgkg SC
9 doses of 20 mgkg IV and
12 doses of 40 mgkg 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:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-I-0017 | None | None | None |