Trial to Evaluate L9LS in Healthy Adults
Condition: Malaria
MeSH terms: Malaria
Intervention: VRC-MALMAB0114-00-AB; Plasmodium falciparum (P. falciparum) sporozoite challenge
Intervention description: VRC-MALMAB0114-00-AB (L9LS) is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozoite protein.; Participants were exposed to bites on the forearm from mosquitoes infected with Plasmodium falciparum
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria Parasitemia; Malaria Challenge; First in Human; Mosquito; Prevention

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 were screened with a medical history, physical exam, and blood tests.

      Participants were divided into 6 groups:

        -  Three groups received L9LS by infusion into a vein, and gave blood samples before and
           after infusion.

        -  One group received L9LS injected into the fat under the skin.

        -  One group did not get L9LS.

        -  One group received L9LS injected into the muscle.

      All participants who received L9LS were monitored for side effects. They had 2-3 follow-up
      visits during the week after the drug was given, and gave blood samples. They received a
      thermometer to check their temperature daily for 7 days. They received a tool to measure any
      redness, swelling, or bruising at the injection site.

      Most participants took part in the controlled human malaria infection (CHMI) or malaria
      challenge to find out if L9LS prevents malaria after being bitten by infected mosquitos.
      Participants in the group who received L9LS injected in the muscle were enrolled after CHMI
      and did not take part in the CHMI. Participants who received CHMI were bitten by mosquitoes
      carrying the malaria parasites. A cup containing mosquitoes was placed on their arm for 5
      minutes. On days 7-17 after exposure, they received daily study visits to give blood samples.
      Those who got malaria were treated immediately. On day 21, all CHMI participants received
      treatment for malaria.

      Participation lasted 2-6 months, depending on study group.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A volunteer must have met 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. White Blood Cell (WBC) 2,500-12,000/mm^3

         14. WBC differential either within institutional normal range or accompanied by the
             Principal Investigator (PI) or designee approval

         15. Platelets = 125,000-500,000/mm^3

         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 polymerase chain reaction (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:

               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 volunteer would have been excluded if one or more of the following conditions applied:

          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

         19. 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