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

NCT01366534 | Completed Phase 2 Results

• 1 other identifier: 114460
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

safety; Vaccine; Phase 1/2; immunogenicity; Malaria; efficacy; sporozoite challenge

Outcome Measures

Primary Outcomes (6)

• Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge

  P. falciparum parasitemia was defined as a positive blood slide.

  28 days following sporozoite challenge (Day 105)

• Number of Subjects With Any and Grade 3 Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were chills, fatigue, gastrointestinal symptoms, headache and temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade.Grade 3 Chills = rigors \[uncontrollable shivering more than (\>) 15 seconds\]. Grade 3 Fatigue, Gastrointestinal symptoms and Headache = symptoms that prevented normal activity. Grade 3 fever = fever higher than (\>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination

• Number of Subjects With Any Unsolicited Adverse Events (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination

• Number of Subjects With Any Unsolicited Adverse Events (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  Within the 30-day (Day 0 - Day 29) follow-up period post-challenge

• Number of Subjects With Serious Adverse Events (SAEs)

  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  Throughout the study period (Day 0 - Day 236)

Secondary Outcomes (9)

• Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge

  From day of challenge (Day 0) up to 159 days post-challenge

• Anti-circumsporozoite Protein (Anti-CS) Antibody Titers

  28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

• Anti-hepatitis B (Anti-HBs) Antibody Titers

  28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

• Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points

  28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

• Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells

  14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Study Arms (3)

Ad35.CS.01 Group

EXPERIMENTAL

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.

Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01); Biological: GSK Biologicals' malaria vaccine 257049 (2 doses)

GSK257049 Group

EXPERIMENTAL

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.

Biological: GSK Biologicals' malaria vaccine 257049 (3 doses)

Control Group

EXPERIMENTAL

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.

Other: Sporozoite challenge

Interventions

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

One dose will be administered intramuscularly at Study Day 0.

Ad35.CS.01 Group

GSK Biologicals' malaria vaccine 257049 (2 doses) BIOLOGICAL

Two doses will be administered intramuscularly at monthly intervals

Ad35.CS.01 Group

GSK Biologicals' malaria vaccine 257049 (3 doses) BIOLOGICAL

Three doses will be administered intramuscularly at monthly intervals

GSK257049 Group

Sporozoite challenge OTHER

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

Control Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

GSK Investigational Site

Silver Spring, Maryland, 20910, United States

Location

Related Publications (3)

• 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.

  PMID: 26148007 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

• 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.

  PMID: 36875126 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2011
• First Posted: June 6, 2011
• Study Start: August 10, 2011
• Primary Completion: February 27, 2012
• Study Completion: July 3, 2012
• Last Updated: June 18, 2019
• Results First Posted: June 9, 2017

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)
• 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)