Phase 1 Clinical Trial With Controlled Human Malaria Infection (CHMI) to Evaluate the Safety and Efficacy of the Plasmodium Falciparum Vaccine Candidate FMP012 Administered Intramuscularly With AS01B Adjuvant System in Healthy Malaria-Naïve Adults

NCT02174978 | Completed Phase 1

• 1 other identifier: S-14-02
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a Phase 1 study with controlled human malaria infection (CHMI) designed primarily to evaluate the safety of the FMP012 combined with AS01B adjuvant system. AS01B is a proprietary current good manufacturing practices (cGMP) grade adjuvant manufactured by GlaxoSmithKline (GSK) Biologicals. It is a formulation based on liposomes mixed with the immunostimulants monophosphoryl lipid (MPL) and Quillaja saponaria (QS)-21. The immunogenicity and efficacy of this new candidate vaccine will be evaluated in addition to safety.

Conditions

Malaria

Keywords

Malaria vaccine

Outcome Measures

Primary Outcomes (3)

• Number of solicited adverse events (AE)

  7 days after each vaccination

• Number of unsolicited AEs

  28 days after each vaccination

• Occurrence of serious adverse events (SAE) at any time during the study period (enrollment to final follow-up visit)

  12 months after vaccination

Secondary Outcomes (2)

• Anti-FMP012 antibody titers in serum

  12 months

• Time to parasitemia by blood smear after the P falciparum challenge

  12 months

Study Arms (3)

Group 1: 10 µg FMP012 adjuvanted AS01B

EXPERIMENTAL

FMP012 with AS01B adjuvant system: 10 µg FMP012 antigen reconstituted with 500 µL AS01B adjuvant to equal 0.5 mL final volume. Doses administered intramuscular at week 0, 4, 8, and 24. On week week 27, there is a P falciparum Controlled Human Malaria Infection (CHMI) challenge.

Biological: FMP012 with AS01B adjuvant system; Other: P falciparum Controlled Human Malaria Infection (CHMI)

Group 2: 30 µg FMP012 adjuvanted AS01B

EXPERIMENTAL

FMP012 with AS01B adjuvant system: 30 µg FMP012 antigen reconstituted with 500 µL AS01B adjuvant to equal 0.5 mL final volume administered intramuscular at week 2, 6, 10, and 24. On week week 27, there is a challenge with P falciparum Controlled Human Malaria Infection (CHMI).

Biological: FMP012 with AS01B adjuvant system; Other: P falciparum Controlled Human Malaria Infection (CHMI)

Infectivity control

OTHER

Non-immunized infectivity control challenged with P falciparum Controlled Human Malaria Infection (CHMI)

Other: P falciparum Controlled Human Malaria Infection (CHMI)

Interventions

FMP012 with AS01B adjuvant system BIOLOGICAL

Candidate malaria vaccine based on the recombinant protein FMP012, which is Escherichia coli-expressed Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS)

Also known as: FMP012 antigen adjuvanted with AS01B

Group 1: 10 µg FMP012 adjuvanted AS01B; Group 2: 30 µg FMP012 adjuvanted AS01B

P falciparum Controlled Human Malaria Infection (CHMI) OTHER

Group 1: 10 µg FMP012 adjuvanted AS01B; Group 2: 30 µg FMP012 adjuvanted AS01B; Infectivity control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults (male or non-pregnant, non-lactating female) 18 to 50 years of age (inclusive) at the time of screening
• If the subject is female,
• Non-childbearing potential (ie, either surgically sterilized or one year post-menopausal), abstinent or using adequate contraceptive precautions (eg, intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®) during this study and must agree to continue such precautions until three months after challenge
• A negative pregnancy test at the time of enrollment
• Free of significant health problems as established by medical history, laboratory, and clinical examination before entering the study
• Subjects must have low cardiac risk factors according to the National Health and Nutrition Examination Survey (NHANES) I criteria, medical history and family history, blood pressure measurements, and a normal or normal variant ECG
• Available to participate and reachable by phone for duration of study (approximately 8-14 months) and reachable by phone at the 6 month post Controlled Human Malaria Infection (CMHI) follow-up
• No plans to travel to outside the Washington DC area between the day of challenge and either completion of treatment course (post-challenge) or, if subject remains uninfected, 28 days 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 are performed
• Subjects must score at least 80% correct on a multiple-choice quiz 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 Rese (WRAIR) Policy 11-45

You may not qualify if:

• Any history of malaria infection
• History of travel to P falciparum endemic areas in the 3 months prior to day of first vaccination (Vaccination Groups) or day of challenge (Infectivity Control Group)
• Any history of receiving a malaria vaccine
• Receipt of any licensed vaccine within 7 days prior to first vaccination (Note: subjects are encouraged to get recommended licensed preventive vaccinations during the course of the study but are requested to schedule any routine preventive vaccinations for at least 7 days before or after a scheduled FMP012/AS01B vaccination day)
• History of receipt of malaria prophylaxis during the 2 months prior to day of first vaccination (Vaccination Groups) or day of challenge (Infectivity Control Group)
• History of use of any antibiotics with significant antimalarial activity (examples include tetracycline, doxycycline, clindamycin, azithromycin, and sulfa drugs) during the course of the study period (period starting one month prior to challenge, Infectivity Control Group)
• 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 (Vaccination Groups)
• Allergy to egg protein (Vaccination Groups)
• Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening or plans to become pregnant or breastfeed from the time of enrollment until three months after challenge
• Allergy to antimalarial drugs or use of medications known to interact with chloroquine (CQ)
• History of sickle cell disease
• History of psoriasis or porphyria
• History of splenectomy
• Any confirmed or suspected immunodeficiency, including HIV infection

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• United States Agency for International Development (USAID): collaborator
• Military Infectious Diseases Research Program (MIDRP): collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Clinical Trials Center, WRAIR

Silver Spring, Maryland, 20910, United States

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• Jason W Bennett, LTC, MC

  Malaria Vaccine Branch, Military Malaria Research Program, WRAIR

  PRINCIPAL INVESTIGATOR

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: June 11, 2014
• First Posted: June 26, 2014
• Study Start: August 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 13, 2017

Record last verified: 2017-10

Locations

US (1)