A Phase I/IIa, Double-blind, Randomized, Placebo-controlled, Dose-escalation Clinical Study Evaluating Safety, Tolerability and Immunogenicity of Two Dose Levels of Recombinant Adenoviral Serotype Ad35 and Serotype Ad26 Vectors Expressing the Malaria Plasmodium Falciparum Circumsporozoite Antigen Administered as Heterologous Prime-boost Regimen, and Assessing Protective Efficacy of the Higher Dose in a Malaria Challenge Model in Unblinded Conditions
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- Crucell Holland BV
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Solicited local and systemic adverse events (AEs)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability and immunogenicity of two dose levels (1x10^10 and 5x10^10 virus particles (vp)) of the adenovirus serotype (Ad) Ad35.CS.01/Ad26.CS.01 prime-boost malaria candidate vaccine, followed by an evaluation of the protective efficacy of the higher dose level in an experimental malaria challenge.
The study will be in 3 phases:
- a dose escalation / vaccination phase in which both dose levels will be tested
- a malaria challenge phase in which only subjects receiving the Ad35.CS.01/Ad26.CS.01 5x10^10 vp dose level, together with six infectivity control subjects, will be exposed to experimental challenge with Plasmodium falciparum
- a long term follow up phase in which all subjects who received active vaccine from both dose levels and/or malaria challenge will be included
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male or non-pregnant female subjects aged ≥18 to ≤50 years on Study Day
- •Able and willing to participate for the duration of the study, to comply with protocol provisions and to undergo malaria challenge.
- •Able and willing to provide written informed consent.
- •Free of obvious health-problems as established by medical history, physical examination, laboratory assessment and clinical judgment of the investigator.
- •If the participant is biologically female she must:
- •Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test performed at screening within 7 days before the 1st vaccine administration, and agree to a urine β-hCG pregnancy test at Study Day 0 and at each subsequent vaccine administration, before the challenge period, and at the end of the challenge period.
- •Agree to consistently use effective contraception from 21 days prior to Study Day 0 for the duration of the study, for sexual activity that could lead to pregnancy.
- •Agree to not seek pregnancy through alternative methods such as artificial insemination or in vitro fertilization until after the last scheduled protocol visit.
- •Male subjects engaged in sexual activities which could lead to pregnancy must agree to use a reliable barrier contraceptive plus spermicide for the duration of the study.
Exclusion Criteria
- •Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have implications for current health status in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to:
- •A process that would affect the immune response,
- •A process that would require medication that affects the immune response,
- •Any contraindication to repeated phlebotomy,
- •A condition or process in which signs or symptoms could be confused with reactions to vaccination or malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation/vaccination, or
- •Any condition specifically listed among the exclusion criteria below.
- •Clinically significant acute illness, including oral temperature \>38.0 °C, or infection within 2 weeks of Study Day 0 that, in the opinion of the Investigator, would interfere with study assessments or cause significant implications for subject safety.
- •History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or (9) other heart conditions under the care of a doctor.
- •Elevated (moderate or high) risk of coronary heart disease as determined by the NHANES I cardiovascular risk assessment criteria.
- •Clinically significant ECG findings, as determined by the study cardiologist.
Outcomes
Primary Outcomes
Solicited local and systemic adverse events (AEs)
Time Frame: For 7 days after each vaccination and at each visit during the challenge period
Type and frequency of solicited local and systemic AEs to be recorded. Solicited AEs in the challenge period are collected via a reactogenicity checklist during study visits. Solicited AEs in the vaccination period are collected via a Subject Diary.
Unsolicited AEs
Time Frame: At each visit during the vaccination period
Type and frequency of unsolicited AEs to be recorded
Vital signs
Time Frame: Before and after each vaccination during the vaccination period, before and after malaria challenge and at each visit during the challenge period
Temperature (oral), pulse, respiratory rate, blood pressure and pulse oximetry will be measured
Changes in laboratory parameters from baseline to end of vaccination phase
Time Frame: Screening/baseline, 7 days after each vaccination, and Days 101 and 115 of the challenge period
Assessment made on the changes in each laboratory parameter from baseline to the end of the vaccination phase at each time point. Parameters measured: Biochemistry: glucose, potassium, creatinine, γ-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, C-reactive protein and erythrocyte sedimentation rate. Hematology: hemoglobin, hematocrit, white blood cell count, white blood cell differential, red blood cell count and platelet count. Urinalysis: leucocytes, blood, protein, ketones and glucose (by dipstick).
Secondary Outcomes
- Efficacy - patent parasitemia(Vaccine recipients are monitored for the development of parasitemia for 28 days post-malaria challenge)
- Immunogenicity(Blood samples drawn at baseline (screening) and Study Days 14, 28, 42, 55/59, 69/73, 86 and 115)