Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults

NCT ID: NCT01366534

Last Updated: 2019-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-10
• Study Completion Date: 2012-07-03

Brief Summary

This study will evaluate whether administration of two investigational malaria vaccines (257049 and Ad35.CS.01 vaccines) combined in one immunization schedule increases protection against malaria infection as compared to protection induced by the 257049 vaccine alone. The study will also evaluate the safety and the immune response to the new combination of the two experimental malaria vaccines.

Detailed Description

Approximately 168 healthy, malaria-naïve volunteers aged 18 - 50 years, divided into 2 groups (84 in each group), will receive either one dose of Ad35.CS.01 followed by two doses of 257049 at monthly intervals or 3 doses of 257049 vaccine at monthly intervals. Of these, a maximum of 138 vaccinated volunteers will be challenged with P. falciparum infected mosquitoes. The challenge will occur 2 weeks following the third immunization. A group of up to 18 infectivity controls will begin participation in the study at the challenge stage. These controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Ad35.CS.01 Group

Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.

Group Type: EXPERIMENTAL

Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)

Intervention Type: BIOLOGICAL

One dose will be administered intramuscularly at Study Day 0.

GSK Biologicals' malaria vaccine 257049 (2 doses)

Intervention Type: BIOLOGICAL

Two doses will be administered intramuscularly at monthly intervals

GSK257049 Group

Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.

Group Type: EXPERIMENTAL

GSK Biologicals' malaria vaccine 257049 (3 doses)

Intervention Type: BIOLOGICAL

Three doses will be administered intramuscularly at monthly intervals

Control Group

Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.

Group Type: EXPERIMENTAL

Sporozoite challenge

Intervention Type: OTHER

Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.

Interventions

Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)

One dose will be administered intramuscularly at Study Day 0.

Intervention Type: BIOLOGICAL

GSK Biologicals' malaria vaccine 257049 (2 doses)

Two doses will be administered intramuscularly at monthly intervals

Intervention Type: BIOLOGICAL

GSK Biologicals' malaria vaccine 257049 (3 doses)

Three doses will be administered intramuscularly at monthly intervals

Intervention Type: BIOLOGICAL

Sporozoite challenge

Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects who the investigator believes 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.
• Female subjects of non-childbearing potential.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced adequate Food and Drug Administration (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.
• Pass a comprehension assessment test.

Exclusion Criteria

• Use of any investigational or non-registered product within 30 days preceding the first dose of study vaccine, or planned use of any investigational or non-registered product other than the study vaccines 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 or adenovirus vaccine.
• Chronic use of antibiotics with antimalarial effects.
• History of malaria chemoprophylaxis within 60 days prior to vaccination.
• Any history of malaria.
• Planned travel to malaria endemic areas during the study period.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s) including latex.
• History of allergic disease or reactions likely to be exacerbated by chloroquine.
• History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.
• Current use of medications known to cause drug reactions to chloroquine, such as antacids and kaolin.
• Any history of anaphylaxis in reaction to any previous vaccination.
• History of severe reactions to mosquito bites.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
• Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to first vaccine dose.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including immunodeficiency virus (HIV) infection.
• Family history of congenital or hereditary immunodeficiency.
• History of splenectomy.
• Major congenital defects or serious chronic illness.
• History of any neurological disorders or seizures.
• Acute disease and/or fever at the time of enrollment.
• 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.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Any abnormal baseline laboratory screening tests.
• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the NHANES I criteria.
• An abnormal baseline screening electrocardiogram (EKG).
• Hepatomegaly, right upper quadrant abdominal pain or tenderness.
• Personal history of autoimmune disease.
• Seropositive for hepatitis B surface antigen or Hepatitis C virus (antibodies to HCV).
• Pregnant or lactating female.
• Female who intends to become pregnant during the study or planning to discontinue contraceptive measures.
• Suspected or known current alcohol abuse.
• Chronic or active intravenous drug use.
• History of blood donation within 56 days preceding enrolment.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The PATH Malaria Vaccine Initiative (MVI)

OTHER

Sponsor Role: collaborator

Crucell Holland BV

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Silver Spring, Maryland, United States

Countries

United States

References

Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, Vekemans J. Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naive Adults. PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26148007 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39377226 (View on PubMed)

Li K, Dodds M, Spreng RL, Abraha M, Huntwork RHC, Dahora LC, Nyanhete T, Dutta S, Wille-Reece U, Jongert E, Ewer KJ, Hill AVS, Jin C, Hill J, Pollard AJ, Munir Alam S, Tomaras GD, Dennison SM. A tool for evaluating heterogeneity in avidity of polyclonal antibodies. Front Immunol. 2023 Feb 16;14:1049673. doi: 10.3389/fimmu.2023.1049673. eCollection 2023.

Reference Type: DERIVED

PMID: 36875126 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

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Other Identifiers

114460

Identifier Type: -

Identifier Source: org_study_id