Efficacy, Safety and Immunogenicity Study of GlaxoSmithKline(GSK) Biologicals' Candidate Malaria Vaccine 257049 in the Sporozoite Challenge Model in Healthy Malaria-naïve Adults

NCT01857869 | Completed Phase 2 Results

• 1 other identifier: 117014
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of GSK Biological's malaria candidate vaccine 257049 administered as standard doses at 0 and 1 months and 1/5th standard dose at 7 months (delayed fractional dose group) and 257049 administered as three standard doses one month apart (0, 1, 2-month group) in healthy malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model. An additional, delayed sporozoite challenge will assess persistence of protection induced by the primary immune schedule and if an additional dose can provide protection in those unprotected by the initial vaccination series.

Conditions

Malaria

Keywords

Efficacy; Sporozoite challenge model; Malaria; Immunogenicity; Malaria- naïve adults; Safety

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge

  The definition of malaria for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.

  28 days post-challenge (Study Day 245)

Secondary Outcomes (21)

• Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge

  Up to 28 days post-challenge (Study Day 245)

• Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge

  Up to 28 days post rechallenge (Booster Phase Day 49)

• Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge

  Up to 28 days post rechallenge (Booster Phase Day 49)

• Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations

  7 days before vaccination (D-7), post-dose 1 at Day 28, post-dose 2 at Days 42, 56, 98, 196, at DoC Primary Phase (PP) (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 14, 28, 42, 56, 70, 84, 159 days (Days 224, 231, 245, 259, 273, 287, 301, 376).

• Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase

  At Day 0 of rechallenge (pre-booster dose) and at DoC PP (Day 217 = Day of rechallenge)

Study Arms (3)

GSK257049-0,1,7M Group

EXPERIMENTAL

Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by another dose of GSK257049 vaccine.

Biological: GSK257049 Dosage 1

GSK257049-0,1,2M Group

EXPERIMENTAL

Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months).

Biological: GSK257049 Dosage 2

Infectivity Control Group

EXPERIMENTAL

Volunteers who did not receive any immunization but underwent sporozoite challenge

Procedure: Sporozoite-infected mosquitoes challenge

Interventions

GSK257049 Dosage 1 BIOLOGICAL

RTS,S/AS01B administered as 0.5 mL dose at 0 and 1 months and 0.1 mL dose at 7 months for 0,1,7 M Group (delayed fractional dose group). In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.

Also known as: S/AS01B, RTS

GSK257049-0,1,7M Group

GSK257049 Dosage 2 BIOLOGICAL

RTS,S/AS01B administered as three doses of 0.5mL given one month apart (0, 1, 2 M group) in the challenge model. In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.

Also known as: RTS, S/AS01B

GSK257049-0,1,2M Group

Sporozoite-infected mosquitoes challenge PROCEDURE

Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the volunteers. For each volunteer, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. The challenge is scheduled to occur approximately 21 days (3 weeks) after the last vaccination visit (Study Day 196). Volunteers who reconsent for the boost/rechallenge phase will be rechallenged with sporozoite-infected mosquitoes, scheduled to occur approximately 21 days (3 weeks) after the booster dose (Booster Phase Study Day 21).

Infectivity Control Group

Eligibility Criteria

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

You may qualify if:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or non-pregnant female 18 to 50 years of age at the time of first vaccination.
• Written informed consent obtained from the subject before screening procedures.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Available to participate for the duration of the study (approximately 15 months per vaccinated subject in the delayed fractional dose group, approximately 10 months per vaccinated subject in the 0, 1, 2-month schedule and approximately 7 months per subject in the infectivity control group).
• Female subjects of non-childbearing potential may be enrolled in the study.
• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
• has practiced adequate FDA-approved contraception for 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination, and
• has agreed to continue adequate FDA-approved contraception during the entire treatment period and for 2 months after completion of the vaccination series and/or malaria challenge.
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject before screening procedures.
• Subjects vaccinated in the primary phase of the study (not applicable to new infectivity controls), having undergone sporozoite challenge during the primary phase of the study.
• Available to participate for the duration of the booster phase of the study (approximately 3 months).

You may not qualify if:

• For enrolment to the primary \& booster phase:
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including immunodeficiency virus (HIV) infection.
• Acute disease and/or fever at the time of enrolment to booster phase.
• Acute disease is defined as the presence of a moderate or severe illness with or without fever. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
• Fever is defined as temperature ≥ 38.0°C (100.4°F) on oral, axillary or tympanic setting. The preferred route for recording temperature in this study will be oral.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National health and nutrition examination survey I (NHANES I) criteria.
• Note: NHANES I criteria will be applied for all subjects including subjects aged 18-35 years old.
• An abnormal baseline screening electrocardiogram (EKG), defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced A-V heart block.
• Female who intends to become pregnant during the study or planning to discontinue contraceptive measures.
• For enrolment to the primary phase:
• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 7 days of the first dose of vaccines.
• Prior receipt of an investigational malaria vaccine.
• Chronic use of antibiotics with antimalarial effects.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• The PATH Malaria Vaccine Initiative (MVI): collaborator

Study Sites (1)

GSK Investigational Site

Silver Spring, Maryland, 20910, United States

Location

Related Publications (3)

• Regules JA, Cicatelli SB, Bennett JW, Paolino KM, Twomey PS, Moon JE, Kathcart AK, Hauns KD, Komisar JL, Qabar AN, Davidson SA, Dutta S, Griffith ME, Magee CD, Wojnarski M, Livezey JR, Kress AT, Waterman PE, Jongert E, Wille-Reece U, Volkmuth W, Emerling D, Robinson WH, Lievens M, Morelle D, Lee CK, Yassin-Rajkumar B, Weltzin R, Cohen J, Paris RM, Waters NC, Birkett AJ, Kaslow DC, Ballou WR, Ockenhouse CF, Vekemans J. Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study. J Infect Dis. 2016 Sep 1;214(5):762-71. doi: 10.1093/infdis/jiw237. Epub 2016 Jun 13.

  PMID: 27296848 BACKGROUND

• Spreng RL, Seaton KE, Lin L, Hilliard S, Horn GQ, Abraha M, Deal AW, Li K, Carnacchi AJ, Feeney E, Shabbir S, Zhang L, Bekker V, Mudrak SV, Dutta S, Mercer LD, Gregory S, King CR, Wille-Reece U, Jongert E, Kisalu NK, Tomaras GD, Dennison SM. Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection. JCI Insight. 2024 Oct 8;9(19):e178801. doi: 10.1172/jci.insight.178801.

  PMID: 39377226 DERIVED

• Oyen D, Torres JL, Wille-Reece U, Ockenhouse CF, Emerling D, Glanville J, Volkmuth W, Flores-Garcia Y, Zavala F, Ward AB, King CR, Wilson IA. Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10438-E10445. doi: 10.1073/pnas.1715812114. Epub 2017 Nov 14.

  PMID: 29138320 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria

Interventions

RTS,S-AS01B vaccine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 20, 2013
• Study Start: May 20, 2013
• Primary Completion: March 24, 2014
• Study Completion: December 16, 2014
• Last Updated: June 26, 2019
• Results First Posted: December 26, 2018

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)