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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: 50 Years

Referral Letter Required


Population Exclusion(s)



Malaria Parasitemia;
Malaria Challenge;
First in Human;

Recruitment Keyword(s)




Investigational Drug(s)


Investigational Device(s)



Drug: VRC-MALMAB0114-00-AB
Other: CHMI

Supporting Site

National Institute of Allergy and Infectious Diseases


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.


To test if the drug L9LS is safe and if it prevents malaria infection in people.


Healthy adults ages 18-50 who have never had malaria.


Participants will be screened with a medical history, physical exam, and blood tests.

Participants will be divided into 6 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 get L9LS injected into the muscle under the skin. This will be Group 6.

-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 (except Group 6) 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.

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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 (except group 6)

11. Agrees to refrain from blood donation to blood banks for 3 years following participation in CHMI (except group 6)

12. 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:

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 PCR for malaria (except Group 6)

21. Negative sickle cell screening test (except Group 6)

22. 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)

23. 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:

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

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

b. Agrees to use an effective means of birth control through the duration of study participation


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 (except Group 6)

12. Known intolerance to chloroquine phosphate, atovaquone or proguanil (except Group 6)

13. Use or planned use of any drug with antimalarial activity that would coincide with study product or CHMI (except Group 6)

14. History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine (except Group 6)

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

16. History of Sjogren s syndrome

17. 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)

18. 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

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Gaudinski MR, Coates EE, Novik L, Widge A, Houser KV, Burch E, Holman LA, Gordon IJ, Chen GL, Carter C, Nason M, Sitar S, Yamshchikov G, Berkowitz N, Andrews C, Vazquez S, Laurencot C, Misasi J, Arnold F, Carlton K, Lawlor H, Gall J, Bailer RT, McDermott A, Capparelli E, Koup RA, Mascola JR, Graham BS, Sullivan NJ, Ledgerwood JE; VRC 608 Study team. Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study. Lancet. 2019 Mar 2;393(10174):889-898. doi: 10.1016/S0140-6736(19)30036-4. Epub 2019 Jan 24. Erratum in: Lancet. 2020 May 30;395(10238):1694. PMID: 30686586; PMCID: PMC6436835.

Seder RA, Chang LJ, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A, Richman A, Chakravarty S, Manoj A, Velmurugan S, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Plummer SH, Hendel CS, Novik L, Costner PJ, Mendoza FH, Saunders JG, Nason MC, Richardson JH, Murphy J, Davidson SA, Richie TL, Sedegah M, Sutamihardja A, Fahle GA, Lyke KE, Laurens MB, Roederer M, Tewari K, Epstein JE, Sim BK, Ledgerwood JE, Graham BS, Hoffman SL; VRC 312 Study Team. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013 Sep 20;341(6152):1359-65. doi: 10.1126/science.1241800. Epub 2013 Aug 8. PMID: 23929949.

Ishizuka AS, Lyke KE, DeZure A, Berry AA, Richie TL, Mendoza FH, Enama ME, Gordon IJ, Chang LJ, Sarwar UN, Zephir KL, Holman LA, James ER, Billingsley PF, Gunasekera A, Chakravarty S, Manoj A, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, K C N, Murshedkar T, DeCederfelt H, Plummer SH, Hendel CS, Novik L, Costner PJ, Saunders JG, Laurens MB, Plowe CV, Flynn B, Whalen WR, Todd JP, Noor J, Rao S, Sierra-Davidson K, Lynn GM, Epstein JE, Kemp MA, Fahle GA, Mikolajczak SA, Fishbaugher M, Sack BK, Kappe SH, Davidson SA, Garver LS, Bj(SqrRoot)(Delta)rkstr(SqrRoot)(Delta)m NK, Nason MC, Graham BS, Roederer M, Sim BK, Hoffman SL, Ledgerwood JE, Seder RA. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med. 2016 Jun;22(6):614-23. doi: 10.1038/nm.4110. Epub 2016 May 9. Erratum in: Nat Med. 2016 Jun 7;22(6):692. PMID: 27158907.

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Principal Investigator

Referral Contact

For more information:

Richard L. Wu, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)

VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715

VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715

Clinical Trials Number:


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