Trial to Evaluate CIS43LS in Healthy Adults
Condition: Malaria
MeSH terms: Malaria
Intervention: VRC-MALMAB0100-00-AB; Plasmodium falciparum (P. falciparum) sporozoite challenge
Intervention description: 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 were exposed to bites on the forearm from Anopheles stephensi mosquitoes infected with P. falciparum (3D7 strain).
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Prevention and Control; Mosquito; Malaria Challenge; Parasitemia; Passive Immunization; Controlled Human Malaria Infection (CHMI)

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 on/with/via 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 participant's study group.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               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 (for all groups except Groups 5, 10, and 16) and < 100 kg for
                  Group 15

               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 4B)

              11. Agrees to refrain from blood donation to blood banks for 3 years following
                  participation in CHMI (except Group 4B)

              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. 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 prior to enrollment:

              20. Negative sickle cell screening test

              21. Negative troponin test (except Group 4B)

              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 4B)

              23. No evidence of increased cardiovascular disease risk; defined as >10% five-year
                  risk by the non-laboratory method (except Group 4B)

                  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:

               1. Woman who is breast-feeding or planning to become pregnant during study
                  participation

               2. Previous receipt of a malaria vaccine

               3. History of malaria infection

               4. History of severe infection with severe acute respiratory syndrome coronavirus 2
                  (SARS-CoV-2) defined per FDA guidance

               5. Active SARS-CoV-2 infection

               6. 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

               7. Hypertension that is not well controlled

               8. Receipt of any investigational study product within 28 days prior to enrollment
                  (note: Emergency Use Authorization Coronavirus Disease 2019 (COVID-19) vaccine is
                  not exclusionary)

               9. Receipt of any live attenuated vaccines within 28 days prior to enrollment

              10. 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

              11. History of a splenectomy, sickle cell disease or sickle cell trait

              12. History of skeeter syndrome or anaphylactic response to mosquito-bites (except
                  Group 4B)

              13. Known intolerance to chloroquine phosphate, atovaquone or proguanil (except Group
                  4B)

              14. Use or planned use of any drug, including antibiotics, with antimalarial activity
                  within 4 weeks prior to CHMI

              15. History of psoriasis or porphyria, which may be exacerbated after treatment with
                  chloroquine (except Group 4B)

              16. Anticipated use of medications known to cause drug reactions with chloroquine or
                  atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and
                  kaolin (except Group 4B)

              17. 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, psychiatric disorders, heart disease, or cancer