Clinical trial NCT03824236: 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
Official title: Efficacy, Immunogenicity and Safety Study Evaluating a Fractional (Fx) Booster Dose of GSK Biologicals' Candidate Malaria Vaccine (SB257049) in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Malaria
RTS,S/AS01E vaccine
Fractional dose
Sporozoite challenge
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: PATH
First posted: 2019-01-31
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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 screening tests: ALT, AST, creatinine, hemoglobin, platelet count, total WBC, out of normal range.
* Personal history of auto-immune disease.
* Administration of immunoglobulins and/or any blood products during the period starting three months before Day 1 (for P-Fx and NP-Fx groups)/the malaria challenge (for infectivity control subjects), or planned administration during the study period.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* History of chronic alcohol consumption and/or drug abuse.
* History of blood donation within 56 days preceding enrollment.
* Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
* 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.

Only for infectivity control subjects:

* Previous vaccination against malaria.
* History of splenectomy.
* Family history of congenital or hereditary immunodeficiency.
* Major congenital defects.
* Serious chronic illness.
* History of any neurological disorders or seizures.
* Diagnosed with malaria within the last 5 years (inclusive).

Primary outcomes:
measure: 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)
timeFrame: During the sporozoite challenge dose follow-up period (from Day 22 up to Day 50)
Secondary outcomes:
measure: Time to Onset of P. Falciparum Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge
timeFrame: During the sporozoite challenge period starting at Day 22 (after the vaccine dose administered at Day 1), up to Day 50
measure: Anti- Circumsporozoite (CS) Repeat Region Antibody Concentrations
timeFrame: At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)
measure: Anti-Hepatitis B (HBs) Immunoglobulin G (IgG) Antibody Concentrations
timeFrame: At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs) in the Booster Vaccination Groups
timeFrame: Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups
measure: Number of Subjects With Any Solicited General AEs in the Booster Vaccination Groups
timeFrame: Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups
measure: Number of Subjects With Any Unsolicited AEs After Vaccination, in the Booster Vaccination Groups
timeFrame: Up to 21 days after booster vaccination period (day of vaccination and 20 subsequent days), after booster vaccination
measure: Number of Subjects With Any Unsolicited AEs After Challenge, in All Study Groups
timeFrame: Within 29 days after challenge (day of challenge and 28 subsequent days)
measure: Number of Subjects With AEs of Specific Interest (Potential Immune-mediated Diseases [pIMDs] and Meningitis), in All Study Groups
timeFrame: From Day 1 up to study conclusion (Day 190)
measure: Number of Subjects With Serious Adverse Events (SAEs) (Any, Fatal or Related to Investigational Vaccine) During the Whole Study Period, in All Study Groups
timeFrame: From Day 1 up to study conclusion (Day 190)
measure: Number of Subjects With Abnormal Laboratory Values
timeFrame: At screening, Day(D)1, D8, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the booster vaccination groups; and at screening, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the infectivity control subjects
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.