Phase 2
N=61
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
Malaria
Bottom Line
View on ClinicalTrials.gov: NCT03824236 ↗Enrolled (actual)
61
Serious AEs
3.3%
Results posted
May 2020
Primary outcome: Primary: 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) — 12; 11; 11 Participants — p=0.003
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- RTS,S/AS01E (SB257049) (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
12; 11; 11 | 0.003 sig |
| SECONDARY Time to Onset of P. Falciparum Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge |
14.6; 14.1; 11.6 | — |
| SECONDARY Anti- Circumsporozoite (CS) Repeat Region Antibody Concentrations |
32.8; 7.2; 87.3; 37.3; 77.8; 25.7 | — |
| SECONDARY Anti-Hepatitis B (HBs) Immunoglobulin G (IgG) Antibody Concentrations |
7788; 6608.1; 25344.5; 29271.3; 21203.1; 19894.8 | — |
| SECONDARY Number of Subjects With Any Solicited Local Adverse Events (AEs) in the Booster Vaccination Groups |
8; 4; 11; 10; 4; 4 | — |
| SECONDARY Number of Subjects With Any Solicited General AEs in the Booster Vaccination Groups |
7; 4; 2; 0; 6; 5 | — |
| SECONDARY Number of Subjects With Any Unsolicited AEs After Vaccination, in the Booster Vaccination Groups |
5; 1 | — |
| SECONDARY Number of Subjects With Any Unsolicited AEs After Challenge, in All Study Groups |
19; 19; 12 | — |
| SECONDARY Number of Subjects With AEs of Specific Interest (Potential Immune-mediated Diseases [pIMDs] and Meningitis), in All Study Groups |
0; 0; 0 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) (Any, Fatal or Related to Investigational Vaccine) During the Whole Study Period, in All Study Groups |
2; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Subjects With Abnormal Laboratory Values |
24; 23; 11; 1; 1; 1 | — |
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.
Eligibility Criteria
Inclusion Criteria
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.
Exclusion Criteria
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.
- Current use of medications known to cause drug reactions that would prevent the subject from utilizing any of the following: chloroquine, atovaquone/proguanil, artemether/lumefantrine.
- History of severe reactions to mosquito bites.
- Acute disease and/or fever at the time of enrollment.
- Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic route.
- Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
- Hepatomegaly, right upper quadrant abdominal pain or tenderness.
- Any abnormal baseline laboratory scr
Data sourced from ClinicalTrials.gov (NCT03824236). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.