A Study to Evaluate the Efficacy, Immunogenicity and Safety in a Sporozoite Challenge Model of a Fractional Booster Dose of GSK Biologicals' Candidate Malaria Vaccine Administered to Previously Vaccinated Healthy Malaria-naïve Adults

NCT03824236 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 20900317337
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

MALARIA-092 (NCT03162614) study was designed to evaluate the efficacy, immunogenicity and safety of various dose schedules and formulations of GSK Biologicals' candidate malaria vaccine (RTS,S/AS01E) in healthy malaria-naïve subjects aged 18-55 years. The purpose of this study (follow-up to MALARIA-092 \[NCT03162614\] study) is to evaluate if protection can be extended with an additional Fx booster dose and if unprotected subjects can be protected following a Fx booster dose. In this booster study, subjects from MALARIA-092 (NCT03162614) study who completed vaccination and challenge will receive a Fx booster dose of RTS,S/AS01E and undergo a second controlled human malaria infection (CHMI) three to four weeks after vaccination. Additionally, subjects will be newly enrolled and will only undergo the sporozoite challenge as infectivity controls.

Conditions

Malaria

Keywords

Malaria; RTS,S/AS01E vaccine; Fractional dose; Sporozoite challenge

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Reporting Plasmodium Falciparum (P. Falciparum) Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge (in All Study Groups 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. P. falciparum infection was defined as asexual blood stage P. falciparum parasite density greater than (\>) 0 detected by blood slide reading. 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 50 - 28 days post challenge).

  During the sporozoite challenge dose follow-up period (from Day 22 up to Day 50)

Secondary Outcomes (10)

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

  During the sporozoite challenge period starting at Day 22 (after the vaccine dose administered at Day 1), up to Day 50

• Anti- Circumsporozoite (CS) Repeat Region Antibody Concentrations

  At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

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

  At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

• Number of Subjects With Any Solicited Local Adverse Events (AEs) in the Booster Vaccination Groups

  Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

• Number of Subjects With Any Solicited General AEs in the Booster Vaccination Groups

  Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

Study Arms (3)

P-Fx group

EXPERIMENTAL

Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.

Biological: RTS,S/AS01E (SB257049)

NP-Fx group

EXPERIMENTAL

Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.

Biological: RTS,S/AS01E (SB257049)

InfectivityCtrl group

NO INTERVENTION

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

Interventions

RTS,S/AS01E (SB257049) BIOLOGICAL

Subjects from the P-Fx and NP-Fx groups will receive one Fx booster dose of RTS,S/AS01E at Day 1.

NP-Fx group; P-Fx group

Eligibility Criteria

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

You may qualify if:

• Only for subjects from MALARIA-092 study (NCT03162614):
• Subjects vaccinated and having undergone sporozoite challenge during the primary study (MALARIA-092 \[NCT03162614\]).
• For all subjects:
• 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 any study-specific procedure.
• 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.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
• Has practiced adequate contraception for 30 days prior to Day 1, and has agreed to continue adequate contraception during the entire treatment period and for two months after malaria challenge (only for subjects from the MALARIA-092 study \[NCT03162614\]).
• Has practiced adequate contraception for 30 days prior to malaria challenge, and has agreed to continue adequate contraception up to two months after malaria challenge (only for the infectivity control subjects).
• Has a negative pregnancy test at enrollment.
• For the infectivity control subjects:
• Male or female subjects between, and including, 18 and 55 years of age.

You may not qualify if:

• For all subjects except the infectivity control subjects:
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of anaphylaxis post-vaccination.
• For all subjects:
• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before Day 1 (Day -29 to Day 1) (for P-Fx and NP-Fx groups)/before the malaria challenge (for infectivity control subjects), or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to Day 1 (for P-Fx and NP-Fx groups) or malaria challenge (for infectivity control subjects). 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 anti-malarial effects.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period within seven days of Day 1 (for P-Fx and NP-Fx groups) or the malaria challenge (for infectivity control subjects).
• 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 Human Immunodeficiency Virus, Hepatitis B surface antigen or Hepatitis C Virus.
• Planned travel to malaria endemic areas during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of any reaction or hypersensitivity that would prevent the subject from utilizing all of the following: chloroquine, atovaquone/proguanil, artemether/lumefantrine.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PATH: collaborator

Study Sites (1)

GSK Investigational Site

Silver Spring, Maryland, 20910, United States

Location

Related Publications (2)

• 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, Greenleaf ME, Regules JA, Debois M, Duncan EH, Sedegah M, Chuang I, Lee CK, Sikaffy AK, Garver LS, Ivinson K, Angov E, Morelle D, Lievens M, Ockenhouse CF, Ngauy V, Ofori-Anyinam O; RTS S Malaria Vaccine Working Group. A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01E in a controlled human malaria infection challenge. Vaccine. 2021 Oct 15;39(43):6398-6406. doi: 10.1016/j.vaccine.2021.09.024. Epub 2021 Sep 27.

  PMID: 34593270 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

RTS malaria 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

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  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: January 29, 2019
• First Posted: January 31, 2019
• Study Start: February 5, 2019
• Primary Completion: April 30, 2019
• Study Completion: September 26, 2019
• Last Updated: August 14, 2020
• Results First Posted: May 15, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• 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)