Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial to Evaluate CIS43LS in Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04206332
Recruitment Status : Recruiting
First Posted : December 20, 2019
Last Update Posted : October 30, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief 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....


Condition or disease Intervention/treatment Phase
Malaria Biological: VRC-MALMAB0100-00-AB Other: CHMI Phase 1

Detailed Description:

Title: VRC 612: A Phase 1, Dose Escalation, Open-Label Clinical Trial with Experimental Controlled Human Malaria Infections (CHMI) to Evaluate the Safety and Protective Efficacy of an Anti- Malaria Human Monoclonal Antibody, VRC-MALMAB0100-00-AB (CIS43LS), in Healthy, Malaria-Na(SqrRoot) ve Adults.

Design: This is the first study of the VRC-MALMAB0100-00-AB (CIS43LS) monoclonal antibody (mAb) targeting the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) in healthy adults. This two-part, dose-escalation, adaptive design study will evaluate the safety, tolerability, pharmacokinetics (PK), and protective efficacy of CIS43LS. The primary hypothesis is that CIS43LS will be safe and tolerable when administered by either intravenous (IV) or subcutaneous (SC) routes. The secondary hypotheses are that CIS43LS will be detectable in human sera with a definable half-life and confer protection following a controlled human malaria infection (CHMI).

Study Product: VRC-MALMAB0100-00-AB was isolated and developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and binds a unique and conserved epitope at the junction of the N- and repeat regions of the PfCSP.

Subjects: Healthy subjects, 18-50 years of age, who are malaria-naive.

Study Plan:

  • Part A: Part A evaluated the doses and routes as shown below in the Study Schema table in an open-label, dose escalation design. The study started with enrollment into Group 1. Safety data show that CIs43LS is safe and tolerble at all dose groups and routes of administration. Preliminary PK data suggest that a gradiant or serum concentrations will be present across groups at the time of CHMI.
  • Part B: Part B will evaluate the doses and routes of CIS43LS needed to reach a threshold

of protection by assessing serum concentration prior to CHMI. Part A veteran subjects will be

invited to participate in Part B and may receive a repeat dose of CIS43LS. New subjects will also enroll into Part B to receive CIS43LS followed by CHMI.

Duration: Subjects who receive CIS43LS will be followed through 24 weeks after product administration. Control subjects will be followed through 8 weeks after CHMI.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 73 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: VRC 612: 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-MALMAB0100-00-AB (CIS43LS), in Healthy, Malaria-Naive Adults
Actual Study Start Date : January 7, 2020
Estimated Primary Completion Date : April 5, 2021
Estimated Study Completion Date : April 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
5mg/kg IV
Biological: VRC-MALMAB0100-00-AB
VRC-MALMAB0100-00-AB is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum circumsporozoite protein. The monoclonal antibody was adapted resulting in an LS mutation found to increase product half-life in plasma.

Other: CHMI
Negative Control designed to test the infection ability of the CHMI

Experimental: Group 2
5mg/kg SC
Biological: VRC-MALMAB0100-00-AB
VRC-MALMAB0100-00-AB is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum circumsporozoite protein. The monoclonal antibody was adapted resulting in an LS mutation found to increase product half-life in plasma.

Other: CHMI
Negative Control designed to test the infection ability of the CHMI

Experimental: Group 3
20 mg/kg IV
Biological: VRC-MALMAB0100-00-AB
VRC-MALMAB0100-00-AB is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum circumsporozoite protein. The monoclonal antibody was adapted resulting in an LS mutation found to increase product half-life in plasma.

Other: CHMI
Negative Control designed to test the infection ability of the CHMI

Experimental: Group 4a
40mg/kg IV
Biological: VRC-MALMAB0100-00-AB
VRC-MALMAB0100-00-AB is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum circumsporozoite protein. The monoclonal antibody was adapted resulting in an LS mutation found to increase product half-life in plasma.

Other: CHMI
Negative Control designed to test the infection ability of the CHMI

Experimental: Group 4b
40 mg/kg IV
Biological: VRC-MALMAB0100-00-AB
VRC-MALMAB0100-00-AB is a monoclonal antibody that recognizes a unique and conserved region of the Plasmodium falciparum circumsporozoite protein. The monoclonal antibody was adapted resulting in an LS mutation found to increase product half-life in plasma.

Other: CHMI
Negative Control designed to test the infection ability of the CHMI

Experimental: Group 5
Control
Other: CHMI
Negative Control designed to test the infection ability of the CHMI




Primary Outcome Measures :
  1. To evaluate the safety and tolerability of CIS43LS [ Time Frame: Through 24 weeks after product administration ]
    5 mg/kg IV of CIS43LS will be administered to healthy, malaria-naive adults.

  2. To evaluate the safety and tolerability of CIS43LS [ Time Frame: Through 24 weeks after product administration ]
    20 mg/kg IV of CIS43LS will be administered to healthy, malaria-naive adults.

  3. To evaluate the safety and tolerability of CIS43LS [ Time Frame: Through 24 weeks after product administration ]
    40 mg/kg IV of CIS43LS will be administered to healthy, malaria-naive adults.

  4. To evaluate the safety and tolerability of CIS43LS [ Time Frame: Through 24 weeks after product administration ]
    5mg/kg SC of CIS43LS will be administered to healthy, malaria-naive adults.


Secondary Outcome Measures :
  1. To evaluate the pharmacokinetics of CIS43LS at each dose level [ Time Frame: Throughout the study ]
    The pharmocokinetics of CIS43LS administered at each dose level will be evaluated.

  2. To determine if CIS43LS confers protection [ Time Frame: Following CHMI ]
    To determine if the administration of CIS43LS confers protection against plasmodium falciparum following CHMI.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 less than or equal to 115 kg (except Group 5 and 10)
  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
  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 COVID-19 infection defined per FDA guidance
  5. Active COVID-19 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
  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 with antimalarial activity that would coincide with study product or CHMI
  15. Routine use of antibiotics, or use of antibiotics within 4 weeks prior to CHMI (except Group 4B)
  16. History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine (except Group 4B)
  17. 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)
  18. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04206332


Contacts
Layout table for location contacts
Contact: VRC Clinic (301) 451-8715 vaccines@nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: VRC Clinic    301-451-8715    vaccines@nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Layout table for investigator information
Principal Investigator: Martin R Gaudinski, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
Publications:
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, Björkström 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.

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04206332    
Other Study ID Numbers: 200017
20-I-0017
First Posted: December 20, 2019    Key Record Dates
Last Update Posted: October 30, 2020
Last Verified: October 28, 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Prevention and Control
Mosquito
Malaria Challenge
Parasitemia
Passive Immunization
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic Diseases