Phase Ib Trial of Two Virosome Formulated Malaria Vaccine Components (PEV 301, PEV 302) in Tanzania (PMAL03)

A Phase Ib Double-blind Randomized Placebo Controlled Age-deescalating Trial of Two Virosome Formulated Anti-malaria Vaccine Components (PEV 301 and PEV 302) Administered in Combination to Healthy Semi-immune Tanzanian Volunteers

This is a phase Ib double-blind randomized placebo controlled age-deescalating trial to assess sagety and immunogenicity of two virosome formulated anti-malaria vaccine components (PEV 301 and PEV 302) administered in combination to healthy semi-immune Tanzanian adult and children.

Study Overview

• Status: Completed
• Conditions: Falciparum Malaria
• Intervention / Treatment: Biological: PEV 301& 302 in virosomes; Biological: Inflexal V (active comparator)

Detailed Description

Volunteers will be screened, enrolled, injected with the vaccine or comparator and followed by the clinicians at the Bagamoyo Research and Training Unit of the the Ifakara Health Research and Development Center (BRTU-IHRDC).

First, 10 adult males will be enrolled and randomized in 2 groups: Group AV (n=8) will be injected with the vaccine combination and group AP (n=2) will be vaccinated with the placebo=comparator (Inflexal V). 5 weeks later, 8 children will be enrolled first and randomized in 2 groups: Group CV (n=6) will be injected with the vaccine combination and group CP (n=2) will be vaccinated with comparator. 1 week later, the rest of the cohort (n=32) will be enrolled and randomized in 2 groups: Group CV (n=26) will be injected with the vaccine combination and group CP (n=6) will be vaccinated with comparator.

Immunogenicity assessments for humoral immune response will be made at baseline (days -10 to -2), day 30 (+4), day 90 (+4) (day of 2nd vaccination), 120 (+4), 180 (+7), and 365 (+14).

Cellular immune responses will be assessed before 1st vaccination (day 0), two weeks after 2nd vaccination (day 104 ±2), and one year after the 1st vaccination (day 365) Safety assessments will be made by the investigator at baseline (days -10 to -2, before the 1st immunization) and at day 1, 2, 3, 7, 14, 30 after each vaccination.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Tanzania
  • Bagamoyo, Tanzania
    • Bagamoyo Research and Training Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male volunteers aged between 18 and 45 years for the adult group, and children of both sexes aged 5-9 years for schoolchildren group
2. Written informed consent obtained from the volunteer (adult) or guardian/ legal representative (children). In case patient is illiterate, an impartial witness should be present during the entire consent procedure
3. Free of obvious health problems as established by medical history and clinical examination before entering the study
4. Body Mass Index between 18 and 30 for adults; MUAC less than 12 for children

Exclusion Criteria:

1. Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period and safety follow-up
2. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose
3. Any chronic drug therapy to be continued during the study period
4. Any confirmed or suspected acquired immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, or history of congenital or hereditary immunodeficiency
5. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
6. Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever (defined as temperature more than 37.5°C)
7. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
8. Acute or chronic diabetes
9. History of chronic alcohol consumption and/or intravenous drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 PEV301&302; The vaccine includes two antigens (CSP and AMA1- derived)in combination and formulated with virosomes	Biological: PEV 301& 302 in virosomes; PEV 301 50 µg plus PEV 302 10 µg formulated in virosomes and injected at day 0 and 90
Active Comparator: 2 Influenza vaccine; Inflexal V is the comparator that includes 3 antigens from flu formulated in virosomes	Biological: Inflexal V (active comparator); Inflexal V is a marketed influenza vaccine that will be given at day 0 and 90

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety (incidence of local and systemic adverse events) Humoral immunity	30 days post-injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Cell-mediated immunity	14 days post-injection

Collaborators and Investigators

• Sponsor: Swiss Tropical & Public Health Institute
• Collaborators: Pevion Biotech Ltd; Mymetics Corporation
• Investigators: Principal Investigator: Blaise Genton, MD PhD, Swiss tropical institute, Ifakara Health Research and Development Center

Publications and helpful links

General Publications

• Cech PG, Aebi T, Abdallah MS, Mpina M, Machunda EB, Westerfeld N, Stoffel SA, Zurbriggen R, Pluschke G, Tanner M, Daubenberger C, Genton B, Abdulla S. Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children. PLoS One. 2011;6(7):e22273. doi: 10.1371/journal.pone.0022273. Epub 2011 Jul 22.

Helpful Links

• Website of the Swiss Tropical Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 8, 2007
• First Posted (Estimate): August 9, 2007

Study Record Updates

• Last Update Posted (Estimate): March 15, 2013
• Last Update Submitted That Met QC Criteria: March 14, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Malaria; Vaccine; Immunogenicity; Phase I; Trial; Falciparum
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum
• Other Study ID Numbers: PMAL03