Phase 1/2a Trial of Pf GAP p52-/p36- Sporozoite Malaria Vaccine

NCT01024686 | Terminated Phase 1 Results DMC

• 1 other identifier: WR 1584
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. falciparum sporozoites. Lastly, the study will assess immunogenicity of p52-/p36- GAP in malaria-naïve healthy adults and preliminary efficacy of p52-/p36- GAP vaccine following primary experimental re-challenge with P. falciparum sporozoites.

Conditions

Malaria

Outcome Measures

Primary Outcomes (5)

• Occurrence of Solicited Adverse Events (AE)

  From administration of study vaccine through 7 days (± 1 days) post dosing

• Occurrence of Unsolicited AEs

  From administration of study vaccine through 28 days (± 4 days) post dosing

• Occurrence of Laboratory Adverse Events (AE)

  Volunteers with any laboratory abnormality.

  From administration of study vaccine through 7 days (± 1 days) post dosing

• Detection of Breakthrough Peripheral Parasitemia by Thick Blood Film

  From 7 days after administration of vaccine through 28 days (+ 4 days) post-dosing

• Occurrence of Serious Adverse Events (SAE)

  baseline through 28 days

Secondary Outcomes (3)

• Development of Parasitemia and Time to Parasitemia After Primary Malaria Challenge Following Administration of GAP

  From administration of study vaccine through the duration of the trial

• Development of Parasitemia and Time to Parasitemia After Re-challenge Following Administration of GAP

  From administration of study vaccine through the duration of the trial

• P. Falciparum Specific Cell-mediated Immune Responses

  From administration of study vaccine through the duration of the trial

Study Arms (3)

p52-p36- GAP Vaccine

EXPERIMENTAL

p52-/p56- GAP Vaccine: Administered by five bites from GAP-infected Anopheles mosquito. p52-/p56- GAP Vaccine: Administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum.

Biological: p52-/p36- GAP Vaccine; Biological: p52-p36- GAP Vaccine

Infectivity Control

NO INTERVENTION

Active Control: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum

p52-p36- GAP Vaccine + Infectivity Challenge

EXPERIMENTAL

p52-/p36- GAP Vaccine: Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum.

Biological: p52-/p36- GAP Vaccine

Interventions

p52-/p36- GAP Vaccine BIOLOGICAL

Administered by five bites from GAP-infected Anopheles mosquito

p52-p36- GAP Vaccine

Eligibility Criteria

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

You may qualify if:

• A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of enrollment
• Free of significant health problems as established by medical history, laboratory assessment and clinical examination before entering into the study
• Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG) as determined by a expert consultant cardiologist
• Available to participate for duration of study
• Reproductive status: a female participant must:
• not be of reproductive potential: i.e. be surgically, medically or physiologically sterile, or
• if engages in sexual activity that could lead to pregnancy:
• agrees to consistently use contraception until 2 months after the last protocol visit. Contraception is defined as using 1 of the following methods:
• condoms (male or female) with or without a spermicide
• diaphragm or cervical cap with spermicide
• intrauterine device (IUD)
• hormonal contraception
• If the volunteer indicates he/she is active duty military (on the DCT sign-in page and intake form), approval from their supervisor through the Division Director using the Statement of Supervisor's Approval Form must be signed and on file prior to receipt of any test product
• Written informed consent must be obtained from the subject before screening procedures
• Prior to entry into this study, subjects must score at least 80% correct on a 10- question multiple-choice quiz that assesses their understanding of this study.

You may not qualify if:

• Prior receipt of any investigational malaria vaccine
• Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
• Administration of any vaccine within 30 days of first study vaccination Any past history of malaria
• Planned travel to malarious areas during the study period
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• A family history of congenital or hereditary immunodeficiency
• Moderate or high 5-year cardiovascular risk as determined by NHANES 1 model
• An abnormal 12-lead electrocardiogram (EKG) suggestive of cardiac disease as determined by a clinician
• Seropositive for HIV, Hepatitis C virus (antibodies to HCV) and/or HBsAg
• Hepatomegaly, right upper quadrant abdominal pain or tenderness
• History of splenectomy
• Chronic or active neurologic disease including seizure disorder and chronic migraine headaches
• History of psoriasis and porphyria
• Acute or chronic, clinically significant pulmonary, cardiovascular, ocular, hematologic, hepatic or renal functional abnormality, as determined by physical examination or abnormal baseline laboratory screening tests and medical history review
• Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

Location

Related Publications (1)

• Spring M, Murphy J, Nielsen R, Dowler M, Bennett JW, Zarling S, Williams J, de la Vega P, Ware L, Komisar J, Polhemus M, Richie TL, Epstein J, Tamminga C, Chuang I, Richie N, O'Neil M, Heppner DG, Healer J, O'Neill M, Smithers H, Finney OC, Mikolajczak SA, Wang R, Cowman A, Ockenhouse C, Krzych U, Kappe SH. First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers. Vaccine. 2013 Oct 9;31(43):4975-83. doi: 10.1016/j.vaccine.2013.08.007. Epub 2013 Sep 8.

  PMID: 24029408 RESULT

Related Links

• First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers.

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Michele Spring
• Organization: U.S. Military Malaria Vaccine Program (USMMVP)

301-319-9307

Study Officials

• Michele Spring, M.D.

  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: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 3, 2009
• Study Start: March 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: October 28, 2019
• Results First Posted: October 28, 2019

Record last verified: 2019-06

Locations

US (1)