A Phase I/IIa Study of the Safety, Immunogenicity and Efficacy of FMP2.1/AS01B, an Asexual Blood-Stage Vaccine for Plasmodium Falciparum Malaria

NCT02044198 | Completed Phase 1

• 2 other identifiers: VAC0542013-004098-28
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate an experimental malaria vaccine for its ability to prevent malaria infection or disease in a blood-stage challenge model (when volunteers are infected with malaria parasites using malaria-infected red blood cells). The vaccine being testing is a protein called FMP2.1, which is given with an adjuvant (a substance to improve the body's response to a vaccination) called AS01B. The aim is to use this protein and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will enable assessment of:

1. 1.The ability of the vaccine to prevent malaria infection.
2. 2.The safety of the vaccine in healthy participants.
3. 3.The response of the human immune system to the vaccine.

Conditions

Plasmodium Falciparum Malaria

Keywords

Plasmodium Falciparum; Malaria; Vaccine; Plasmodium; Falciparum

Outcome Measures

Primary Outcomes (1)

• PCR-derived parasite multiplication rate (PMR)

  PCR-derived parasite multiplication rate (PMR) will be the primary study endpoint, and comparison of the endpoint between the two study groups will constitute the primary analysis for efficacy.

  From the day before CHMI until 23 days after the challenge

Study Arms (2)

Group 1 - FMP2.1/AS01B vaccine

ACTIVE COMPARATOR

FMP2.1/AS01B vaccine administered at days 0, 28 and 56. Blood-stage controlled human malaria infection (CHMI) at day 70.

Biological: FMP2.1/AS01B

Group 2 - control

NO INTERVENTION

Group 2 is an infectivity-control group for the malaria infection challenge procedures; these volunteers will not be vaccinated. Blood-stage controlled human malaria infection (CHMI) at day 70.

Interventions

FMP2.1/AS01B BIOLOGICAL

50 µg FMP2.1 in 0.5 mL of the adjuvant AS01B (containing 50 mcg MPL + 50 mcg QS21) is administered via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Also known as: FMP2.1, AS01B

Group 1 - FMP2.1/AS01B vaccine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, male or non-pregnant female adults aged 18 - 45 years
• Subject is willing and able to give written informed consent for participation in the study
• Resident in or near Oxford for the duration of the challenge part of the study. Or for volunteers not living in Oxford: agreement to stay in arranged accommodation close to the trial centre during a part of the study (from the day before challenge until anti-malarial treatment is completed).
• Female subjects of child bearing potential must be willing to ensure that they practice continuous effective contraception for the duration of the study
• Able (in the Investigator's opinion) and willing to comply with all study requirements
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study
• Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines (73).
• Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment.
• Willingness to take a curative anti-malaria regimen following CHMI.
• Answer all questions on the informed consent questionnaire correctly.

You may not qualify if:

• History of clinical malaria (any species).
• Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
• Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
• Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data.
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• Use of immunoglobulins or blood products within 3 months prior to enrolment or previous severe adverse reaction to a blood transfusion.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (or malaria infection).
• Any history of anaphylaxis post vaccination.
• Pregnancy, lactation or intention to become pregnant during the study.
• Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone.
• Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone.
• Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone and Chloroquine.
• Any clinical condition known to prolong the QT interval.

Sponsors & Collaborators

• University of Oxford: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (3)

NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

NIHR Wellcome Trust Clinical Research Facility (NIHR WTCRF), Hammersmith Hospital

London, London, W2 1NY, United Kingdom

Location

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Payne RO, Milne KH, Elias SC, Edwards NJ, Douglas AD, Brown RE, Silk SE, Biswas S, Miura K, Roberts R, Rampling TW, Venkatraman N, Hodgson SH, Labbe GM, Halstead FD, Poulton ID, Nugent FL, de Graaf H, Sukhtankar P, Williams NC, Ockenhouse CF, Kathcart AK, Qabar AN, Waters NC, Soisson LA, Birkett AJ, Cooke GS, Faust SN, Woods C, Ivinson K, McCarthy JS, Diggs CL, Vekemans J, Long CA, Hill AV, Lawrie AM, Dutta S, Draper SJ. Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01. J Infect Dis. 2016 Jun 1;213(11):1743-51. doi: 10.1093/infdis/jiw039. Epub 2016 Feb 4.

  PMID: 26908756 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• Simon J Draper

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Saul N Faust

  University of Southampton

  PRINCIPAL INVESTIGATOR

• Graham S Cooke

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 23, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 9, 2015

Record last verified: 2015-01

Locations

GB (3)