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 Heal

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Criteria

• INCLUSION CRITERIA:

A subject must meet all of the following criteria to be included:

1. Able and willing to complete the informed consent process

2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

3. Available for clinical follow-up through the last study visit

4. 18 to 50 years of age

5. In good general health without clinically significant medical history

6. Physical examination without clinically significant findings within the 56 days prior to enrollment

7. Weight <= 115 kg (except Group 5)

8. Adequate venous access if assigned to an IV group or adequate subcutaneous tissue if assigned to an SC group

9. Willing to have blood samples collected, stored indefinitely, and used for research purposes

10. Agrees to participate in a controlled human malaria infection (CHMI) and to comply with post-CHMI follow-up requirements

11. Agrees to refrain from blood donation to blood banks for 3 years following participation in CHMI

12. Agrees not to travel to a malaria endemic region during the entire course of study participation

Laboratory Criteria within 56 days prior to enrollment:

13. WBC 2,500-12,000/mm3

14. WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval

15. Platelets = 125,000 500,000/mm3

16. Hemoglobin within institutional normal range or accompanied by the PI or designee approval

17. Creatinine <= 1.1 x upper limit of normal (ULN)

18. Alanine aminotransferase (ALT) <=1.25 x ULN

19. Negative for HIV infection by an FDA approved method of detection

Laboratory Criteria documented any time during screening, prior to enrollment:

20. Negative sickle cell screening test

21. 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

22. No evidence of increased cardiovascular disease risk; defined as >10% five-year risk by the non-laboratory method

Criteria Specific to Women:

23. Postmenopausal for at least 1 year, post-hysterectomy or bilateral oophorectomy, or if of childbearing potential:

1. Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on day of enrollment, and prior to product administration and CHMI, and

2. 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:

1. Woman who is breast-feeding or planning to become pregnant during study participation

2. Previous receipt of a malaria vaccine or anti-malaria monoclonal antibody

3. History of malaria infection

4. 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

5. Hypertension that is not well controlled

6. 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)

7. Receipt of any live attenuated vaccines within 28 days prior to enrollment/product administration

8. Receipt of any vaccine within 2 weeks prior to enrollment/product administration

9. 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

10. History of a splenectomy, sickle cell disease or sickle cell trait

11. History of skeeter syndrome or anaphylactic response to mosquito-bites

12. Known intolerance to chloroquine phosphate, atovaquone or proguanil

13. Use or planned use of any drug with antimalarial activity that would coincide with study product or CHMI

14. Routine use of antibiotics, or use of antibiotics within 4 weeks prior to CHMI

15. History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine

16. Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin

17. History of Sjogren s syndrome

18. 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)

19. History of therapeutic head or neck radiation

20. 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