Study of VMP001 and AS01B (Adjuvant Formulation) in Healthy Malaria-Naïve Adults

NCT01157897 | Completed Phase 1 Results DMC

• 2 other identifiers: WRAIR 1692IND 14380
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-humans safety, immunogenicity and efficacy study with recombinant protein VMP001, a Plasmodium vivax circumsporozoite (CS) protein based vaccine. This open label study will be performed in malaria-naïve adults in the United States. Three doses of VMP001 formulated in AS01B (adjuvant system) will be given intramuscularly at different intervals followed by a challenge with P. vivax infected mosquitoes. Safety, immunogenicity and efficacy parameters will be studied.

Conditions

Malaria; Plasmodium Vivax

Keywords

Malaria; Plasmodium Vivax; Vaccine

Outcome Measures

Primary Outcomes (3)

• Occurrence of Solicited Adverse Events Over a 7 Day Follow-up Period After Each Immunization (the Day of the Immunization and 6 Subsequent Days) During the Vaccination Phase

  Adverse events were evaluated for 7 days after each vaccination during the vaccine phase.

  7 days after immunization

• Occurrence of Unsolicited Adverse Events Over a 28 Day Follow-up Period After Each Immunization (the Day of the Immunization and 27 Subsequent Days) During the Vaccination Phase

  Adverse events were evaluated over a 28 day follow-up period after each vaccination during the vaccine phase

  28 days following immunization

• Occurrence of Serious Adverse Events at Any Time During the Study Period (Enrollment to Final Follow up Visit)

  Occurrence of serious adverse events at any time during the approximately 463 day study period

  up to 463 days

Secondary Outcomes (3)

• Time to Parasitemia for Immunogenicity Population

  280 day (during the study through 6 months aftr challenge)

• Geometric Mean of Anti-VMP001 Antibody Titers in Serum Per Immunogenicity Population

  study duration

• Geometric Mean of Anti-VMP001 Anti-body Titers in Serum Per Efficacy Population

  study duration

Study Arms (4)

Cohort 1: 15 μg VMP001

EXPERIMENTAL

15ug VMP001 per vaccination on days -1 or 0, 28, and 84. P. vivax sporozoite challenge on day 98.

Biological: VMP001; Other: P. vivax sporozoite challenge

Cohort 2: 30 μg VMP001

EXPERIMENTAL

30ug VMP001 per vaccination on days 14, 42, and 84. P. vivax sporozoite challenge on day 98.

Biological: VMP001; Other: P. vivax sporozoite challenge

Cohort 3: 60 μg VMP001

EXPERIMENTAL

60ug VMP001 per vaccination on days 28, 56, and 84. P. vivax sporozoite challenge on day 98.

Biological: VMP001; Other: P. vivax sporozoite challenge

Control

OTHER

No Vaccinations given for controls. P. vivax sporozoite challenge on day 98.

Other: P. vivax sporozoite challenge

Interventions

VMP001 BIOLOGICAL

Plasmodium vivax malaria protein 001 (VMP001) with GSK Biologicals' Adjuvant System AS01B

Cohort 1: 15 μg VMP001; Cohort 2: 30 μg VMP001; Cohort 3: 60 μg VMP001

P. vivax sporozoite challenge OTHER

P. vivax sporozoite challenge

Cohort 1: 15 μg VMP001; Cohort 2: 30 μg VMP001; Cohort 3: 60 μg VMP001; Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who meet all of the following criteria may participate in this study:
• Healthy adults (male or non-pregnant, non-lactating female) 18 to 55 years of age (inclusive) at the time of enrollment
• If the subject is female, she must be of non-childbearing potential (either surgically sterilized or one year post-menopausal) or, if of childbearing potential, she must be capable of preventing pregnancy, have a negative pregnancy test at the time of each vaccination, and must agree to continue such precautions until completion of the last study visit.
• Free of significant health problems as established by medical history, laboratory and clinical examination before entering the study
• Duffy positive phenotype (homozygous or heterozygous)
• Normal (non-deficient) Glucose 6-phosphate dehydrogenase (G6PD) phenotype (range: 4.6 to 13.5 units/gm hemoglobin)
• Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG)
• Available to participate and reachable by phone for duration of study (approximately 9 months)
• No plans to travel to outside the Washington, District of Columbia (DC) area up until treatment course has been completed (post challenge)
• No plans to travel to a malaria endemic area during the course of the study
• Written informed consent must be obtained from the subject before screening procedures
• Volunteers must score at least 80% correct on a 10 or 14 question multiple-choice quiz (control and immunization groups, respectively) that assesses their understanding of this study
• If a subject is active duty military he or she must obtain approval from his or her supervisor per Walter Reed Army Institute of Research (WRAIR) Policy 06-15

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Any history of malaria infection
• History of travel to P. vivax endemic areas in the last three months, and travel to Republic of Korea or China in the last 18 months
• Any history of receiving malaria vaccine or any licensed vaccine within 7 days prior to first immunization
• History of receipt of malaria prophylaxis during the previous 2 months or the use of any drugs with significant anti-malarial activity during the study period one month prior to challenge (for control volunteers). Examples include tetracycline, doxycycline, clindamycin, azithromycin or sulfa drugs
• Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine or planned use during the study period.
• Any history of allergic reaction or anaphylaxis to previous vaccination
• Allergy to kanamycin, nickel, or imidazole
• Pregnant (positive β-HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until study completion.
• Allergy to antimalarial drugs or use of medications known to cause drug reactions with chloroquine and/or primaquine
• History of sickle cell disease
• History of psoriasis or porphyria
• History of splenectomy
• Any confirmed or suspected immunodeficiency, including HIV infection
• Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune-modifying drugs within 6 months of immunization. For corticosteroids, this is defined as \>20 mg/day prednisone or equivalent. -Inhaled and topical steroids are allowed

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• United States Department of Defense: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Clinical Trials Center, Walter Reed Army Institute of Reserach

Silver Spring, Maryland, 20910, United States

Location

Related Publications (2)

• Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013 Oct 3;369(14):1381-2. doi: 10.1056/NEJMc1301936. No abstract available.

  PMID: 24088113 RESULT

• Kamau E, Bennett JW, Yadava A. Safety and Tolerability of Mosquito Bite-Induced Controlled Human Infection with Plasmodium vivax in Malaria-Naive Study Participants-Clinical Profile and Utility of Molecular Diagnostic Methods. J Infect Dis. 2022 Jan 5;225(1):146-156. doi: 10.1093/infdis/jiab332.

  PMID: 34161579 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Donna Tosh
• Organization: WRAIR

donna.m.tosh.ctr@mail.mil

301-319-9332

Study Officials

• Jason Bennett, MD

  Division of Malaria Vaccine Development (DMVD), Walter Reed Army Institute of Research (WRAIR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 7, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: May 29, 2019
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Locations

US (1)