Trial to Evaluate CIS43LS in Healthy Adults

• Status: Recruiting
• Trial end date: 2022-04-05
• Target enrollment: 0
• Participant gender: All

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 a drug called CIS43LS that could prevent malaria infection.

Eligibility:

Healthy people ages 18-50 who have never been infected with malaria

Design:

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

Some participants will get pregnancy tests.

Most participants will get CIS43LS. They will get the drug infused into a vein in their arm or injected into the fat under the skin. They will be monitored for side effects for up to 4 hours after they get the drug.

Participants will be given a thermometer to check their temperature every day for 7 days. They will also be given a device to measure any redness, swelling, or bruising at the injection site.

Participants will have up to 12 follow-up visits. These will include blood tests.

Most participants will take part in a Controlled Human Malaria Challenge (CHMI). During the CHMI, mosquitoes carrying the malaria parasite will bite participants in a controlled setting. The participants will then have clinic visits every day for up to 12 days starting 7 days after the CHMI. They will be treated right away with antimalarial medication if the test shows positive for malaria. If participants continue to test negative for malaria, they will have 2 more visits over the next 6 days for blood tests. Then 28 days after the CHMI they will get treated with antimalarial medication for 3 days. The study will last 2-6 months depending on participants 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 (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. 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 - 400,000/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:

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

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 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