Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults

NCT03162614 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 205081
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate efficacy, immunogenicity and safety of various dose schedules of GSK Biologicals' candidate malaria vaccines RTS,S/AS01B (adult formulation) and RTS,S/AS01E (pediatric formulation) in healthy malaria-naïve subjects aged 18-55 years. The purpose of this study is to investigate whether changes in dosing schedule are associated with increased or equivalent protection, and to evaluate the immune mechanisms associated with vaccine efficacy under varying dosing schedules.

Conditions

Malaria

Keywords

healthy volunteers; Malaria; malaria vaccine; controlled human challenge; RTS,S/AS01

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls

  Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol defined post challenge follow-up (Day 315 - 28 days post challenge).

  Following sporozoite challenge starting 3 months after the last vaccine dose (Day 287) for up to 28 days post-challenge (Day 315).

Secondary Outcomes (14)

• Time to Onset of P. Falciparum Parasitemia After Sporozoite Challenge for Each Vaccination Schedule

  Following sporozoite challenge starting 3 months after the last vaccine dose (at Day 287) for up to 28 days post-challenge (at Day 315).

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

  At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group

• Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations

  At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group

• Number of Subjects With Any Solicited Local Symptoms

  Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.

• Number of Subjects With Any Solicited General Symptoms

  Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.

Study Arms (6)

AduFx Group

ACTIVE COMPARATOR

Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge.

Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.

2PedFx Group

EXPERIMENTAL

Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge.

Biological: RTS,S/AS01E; Procedure: Sporozoite-infected mosquitoes challenge.

PedFx Group

EXPERIMENTAL

Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge.

Biological: RTS,S/AS01E; Procedure: Sporozoite-infected mosquitoes challenge.

Adu2Fx Group

EXPERIMENTAL

Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge.

Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.

Adu1Fx Group

ACTIVE COMPARATOR

Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge.

Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.

Control Group

OTHER

Healthy subjects, between, and including, 18 and 55 years of age, who did not receive any immunization but underwent sporozoite challenge.

Procedure: Sporozoite-infected mosquitoes challenge.

Interventions

RTS,S/AS01E BIOLOGICAL

Subjects will receive intramuscular injection of RTS,S/AS01E.

2PedFx Group; PedFx Group

RTS,S/AS01B BIOLOGICAL

Subjects will receive intramuscular injection of RTS,S/AS01B.

Adu1Fx Group; Adu2Fx Group; AduFx 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 subjects. For each subject, 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. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed. The challenge occurs approximately 90 days (three months) after the last vaccination. Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.

2PedFx Group; Adu1Fx Group; Adu2Fx Group; AduFx Group; Control Group; PedFx Group

Eligibility Criteria

• Age: 18 Years - 55 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.
• Written informed consent obtained from the subject prior to performing of any study specific procedure.
• A male or female between, and including, 18 and 55 years of age at the time of enrolment.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Available to participate for the duration of the study.
• 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 contraception for 30 days prior to vaccination, and
• has a negative pregnancy test at enrolment, and
• has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series and/or malaria challenge.

You may not qualify if:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period.
• Chronic use of antibiotics with antimalarial effects.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Documented HIV-positive subject.
• Previous vaccination against malaria.
• History of malaria chemoprophylaxis within 60 days prior to vaccination.
• Any history of malaria (for the vaccine groups).
• Planned travel to malaria endemic areas during the study period.
• History of splenectomy.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator

Study Sites (1)

GSK Investigational Site

Silver Spring, Maryland, 20910, United States

Location

Related Publications (3)

• James E. Moon, Christian Ockenhouse, Jason A. Regules, Johan Vekemans, Cynthia Lee, Ilin Chuang, Magali Traskine, Erik Jongert, Karen Ivinson, Danielle Morelle, Jack L. Komisar, Marc Lievens, Martha Sedegah, Lindsey Garver, April K. Sikaffy, Norman C. Waters, William Ripley Ballou, Opokua Ofori-Anyinam for the RTS,S Malaria Vaccine Working Group. CLI_092_A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naïve Adults. J Infect Dis. 2020 Jul 20;jiaa421. doi: 10.1093/infdis/jiaa421. Online ahead of print.

  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

• Moon JE, Ockenhouse C, Regules JA, Vekemans J, Lee C, Chuang I, Traskine M, Jongert E, Ivinson K, Morelle D, Komisar JL, Lievens M, Sedegah M, Garver LS, Sikaffy AK, Waters NC, Ballou WR, Ofori-Anyinam O; RTS,S Malaria Vaccine Working Group. A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults. J Infect Dis. 2020 Oct 13;222(10):1681-1691. doi: 10.1093/infdis/jiaa421.

  PMID: 32687161 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

RTS malaria vaccine; 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

GSKClinicalSupportHD@gsk.com

877-379-3718

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: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 22, 2017
• Study Start: May 24, 2017
• Primary Completion: July 9, 2018
• Study Completion: September 24, 2018
• Last Updated: October 27, 2020
• Results First Posted: July 24, 2019

Record last verified: 2020-10

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 (copy the URL below to your browser)
• 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)