VRC 614: 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-MALMAB0114-00-AB (L9LS), in Healt...
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05019729 |
|
Recruitment Status :
Active, not recruiting
First Posted : August 25, 2021
Last Update Posted : October 14, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Background:
Malaria is a parasitic disease carried by mosquitoes in tropical areas. There is no vaccine to prevent malaria infection. If not treated right away, it can become serious or deadly. Researchers want to test a drug to prevent malaria.
Objective:
To test if the drug L9LS is safe and if it prevents malaria infection in people.
Eligibility:
Healthy adults ages 18-50 who have never had malaria.
Design:
Participants will be screened with a medical history, physical exam, and blood tests.
Participants will be divided into 5 groups:
- Three groups will get L9LS by infusion into a vein. They will give blood samples before and after infusion.
- One group will get L9LS injected into the fat under the skin.
- One group will not get L9LS.
All participants who get L9LS will be monitored for side effects. They will have 2-3 follow-up visits during the week after the drug is given. They will give blood samples. They will get a thermometer to check their temperature daily for 7 days. They will get a tool to measure any redness, swelling, or bruising at the injection site.
All participants will be bitten by mosquitoes carrying the malaria parasites. A cup containing mosquitoes will be placed on their arm for 5 minutes. On days 7-17 after exposure, they will have daily study visits to give blood samples. Those who get malaria will be treated immediately. On day 21, all participants will get treatment for malaria.
Participation will last 2-6 months, depending on study group.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Malaria | Drug: VRC-MALMAB0114-00-AB Other: CHMI | Phase 1 |
This is a Phase 1, open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and protective efficacy of an anti-malaria human monoclonal antibody, VRC-MALMAB0114-00-AB (L9LS). The primary hypothesis is that L9LS will be safe and well tolerated when administered by either intravenous (IV),subcutaneous (SC) or intramuscular (IM) routes. The secondary objectives are that L9LS will be detectable in human sera with a definable half-life and confer protection following a controlled human malaria infection (CHMI).
The study will start with enrollment into Group 1. Interim safety evaluations will occur and must support continued evaluation of L9LS prior to enrolling subjects into additional dose groups. All L9LS recipients in Groups 1-4 will participate in the CHMI. Group 5 participants will not receive investigational product, in order to serve as the control group for the CHMI. After CHMI, all participants will be evaluated for malaria parasitemia. Subjects who develop blood stage infection will be treated as soon as identified per protocol criteria. Subjects in Group 6 will receive investigational product but will not take part in the CHMI.
Study follow-up will continue through 24 weeks post product administration or 8 weeks post CHMI, whichever is most stringent.
The groups are:
Group 1: 5 subjects- 1mg/kg IV
Group 2: 4 subjects- 5 mg/kg IV
Group 3: 5 subjects - 5 mg/ kg SC
Group 4: 4 subjects - 20 mg/kg IV
Group 5: 6 subjects - Control
Group 6: 5 subjects- 5 mg/kg IM
Enrollment of up to 40 subjects is permitted. Two additional subjects will be enrolled as CHMI back-ups.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 32 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | VRC 614: 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-MALMAB0114-00-AB (L9LS), in Healthy Malaria-Naive Adults |
| Actual Study Start Date : | September 13, 2021 |
| Actual Primary Completion Date : | September 19, 2022 |
| Estimated Study Completion Date : | December 31, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Group 1
1 mg/kg IV
|
Drug: VRC-MALMAB0114-00-AB
VRC-MALMAB0114-00-AB is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozite protein. Other: CHMI Negative control designed to test the infection ability of the CHMI. |
|
Experimental: Group 2
5 mg/kg IV
|
Drug: VRC-MALMAB0114-00-AB
VRC-MALMAB0114-00-AB is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozite protein. Other: CHMI Negative control designed to test the infection ability of the CHMI. |
|
Experimental: Group 3
5 mg/kg SC
|
Drug: VRC-MALMAB0114-00-AB
VRC-MALMAB0114-00-AB is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozite protein. Other: CHMI Negative control designed to test the infection ability of the CHMI. |
|
Experimental: Group 4
20 mg/kg IV
|
Drug: VRC-MALMAB0114-00-AB
VRC-MALMAB0114-00-AB is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozite protein. Other: CHMI Negative control designed to test the infection ability of the CHMI. |
|
No Intervention: Group 5
Nothing
|
|
|
Experimental: Group 6
5 mg/kg IM
|
Drug: VRC-MALMAB0114-00-AB
VRC-MALMAB0114-00-AB is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozite protein. |
- To evaluate the safety and tolerability of L9LS [ Time Frame: Through 24 weeks after product administration ]20 mg/kg IV of L9LS administered to healthy malaria-naive adults.
- To evaluate the safety and tolerability of L9LS [ Time Frame: Through 24 weeks after product administration ]1 mg/kg IV of L9LS administered to healthy malaria-naive adults.
- To evaluate the safety and tolerability of L9LS [ Time Frame: Through 24 weeks after product administration ]5 mg/kg IV of L9LS administered to healthy malaria-naive adults.
- To evaluate the safety and tolerability of L9LS [ Time Frame: Through 24 weeks after product administration ]5 mg/kg IM of L9LS will be administered to healthy malaria-naive adults.
- To evaluate the safety and tolerability of L9LS [ Time Frame: Through 24 weeks after product administration ]5 mg/kg SC of L9LS will be administered to healthy malaria-naive adults.
- To evaluate the phamacokinetics of L9LS at each dose level [ Time Frame: Throughout the study ]The pharmacokinetics of L9LS administered at each dose level will be evaluated.
- To determine if L9LS confers protection [ Time Frame: Following CHMI ]To determine if L9LS administered IV or SC confers protection against plasmodium falciparum following CHMI
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
A subject must meet all of the following criteria to be included:
- Able and willing to complete the informed consent process
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- Available for clinical follow-up through the last study visit
- 18 to 50 years of age
- In good general health without clinically significant medical history
- Physical examination without clinically significant findings within the 56 days prior to enrollment
- Weight <= 115 kg (except Group 5)
- Adequate venous access if assigned to an IV group or adequate subcutaneous tissue if assigned to an SC group
- Willing to have blood samples collected, stored indefinitely, and used for research purposes
- Agrees to participate in a controlled human malaria infection (CHMI) and to comply with post-CHMI follow-up requirements (except group 6)
- Agrees to refrain from blood donation to blood banks for 3 years following participation in CHMI (except group 6)
-
Agrees not to travel to a malaria endemic region during the entire course of study participation (except group 6)
Laboratory Criteria within 56 days prior to enrollment:
- WBC 2,500-12,000/mm3
- WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval
- Platelets = 125,000 500,000/mm3
- Hemoglobin within institutional normal range or accompanied by the PI or designee approval
- Creatinine <= 1.1 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) <=1.25 x ULN
-
Negative for HIV infection by an FDA approved method of detection
Laboratory Criteria documented any time during screening, prior to enrollment:
- Negative PCR for malaria (except Group 6)
- Negative sickle cell screening test (except Group 6)
- Electrocardiogram (ECG) without clinically significant abnormalities (examples may include: pathologic Q waves, significant ST-T wave changes, left ventricular hypertrophy, any non-sinus rhythm excluding isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block). ECG abnormalities determined by a cardiologist to be clinically insignificant as related to study participation do not preclude study enrollment (except Group 6)
-
No evidence of increased cardiovascular disease risk; defined as >10% five-year risk by the non-laboratory method (except Group 6)
Criteria Specific to Women:
-
Postmenopausal for at least 1 year, post-hysterectomy or bilateral oophorectomy, or if of childbearing potential:
- Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on day of enrollment, and prior to product administration and CHMI, and
- Agrees to use an effective means of birth control through the duration of study participation
EXCLUSION CRITERIA:
A subject will be excluded if one or more of the following conditions apply:
- Woman who is breast-feeding or planning to become pregnant during study participation
- Previous receipt of a malaria vaccine or anti-malaria monoclonal antibody
- History of malaria infection
- Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study
- Hypertension that is not well controlled
- Receipt of any investigational study product within 28 days prior to enrollment/product administration (Note: SARS-CoV-2 vaccines approved by emergency use authorization are not exclusionary)
- Receipt of any live attenuated vaccines within 28 days prior to enrollment/product administration
- Receipt of any vaccine within 2 weeks prior to enrollment/product administration
- Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws
- History of a splenectomy, sickle cell disease or sickle cell trait
- History of skeeter syndrome or anaphylactic response to mosquito-bites (except Group 6)
- Known intolerance to chloroquine phosphate, atovaquone or proguanil (except Group 6)
- Use or planned use of any drug with antimalarial activity that would coincide with study product or CHMI (except Group 6)
- History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine (except Group 6)
- Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin
- History of Sjogren s syndrome
- History of chronic or recurrent salivary gland disorder diagnosed by a clinician (note: an isolated occurrence of parotitis, sialadenitis, sialolithiasis, or of a salivary gland tumor is not exclusionary)
- History of therapeutic head or neck radiation
29. Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer, including but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, infectious diseases, psychiatric disorders, heart disease, or cancer
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05019729
| United States, Maryland | |
| National Institutes of Health Clinical Center | |
| Bethesda, Maryland, United States, 20892 | |
| Principal Investigator: | Richard L Wu, M.D. | National Institute of Allergy and Infectious Diseases (NIAID) |
Documents provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT05019729 |
| Other Study ID Numbers: |
10000536 000536-I |
| First Posted: | August 25, 2021 Key Record Dates |
| Last Update Posted: | October 14, 2022 |
| Last Verified: | September 26, 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | .Only aggregate data will be shared. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Malaria Parasitemia Malaria Challenge First in Human Mosquito Prevention |
|
Malaria Infections Protozoan Infections Parasitic Diseases Vector Borne Diseases |