A Study to Assess the Immunogenicity, Tolerability and Safety of a Malaria Vaccine and Also Its Protective Efficacy in a Malaria Challenge Model

NCT01397227 | Completed Phase 1 DMC

• 1 other identifier: MAL-V-A001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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:

1. 1.a dose escalation / vaccination phase in which both dose levels will be tested
2. 2.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
3. 3.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

Conditions

Malaria

Keywords

Malaria; Plasmodium falciparum; Vaccination; Prophylaxis; Adenovirus

Outcome Measures

Primary Outcomes (4)

• Solicited local and systemic adverse events (AEs)

  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.

  For 7 days after each vaccination and at each visit during the challenge period

• Unsolicited AEs

  Type and frequency of unsolicited AEs to be recorded

  At each visit during the vaccination period

• Vital signs

  Temperature (oral), pulse, respiratory rate, blood pressure and pulse oximetry will be measured

  Before and after each vaccination during the vaccination period, before and after malaria challenge and at each visit during the challenge period

• Changes in laboratory parameters from baseline to end of vaccination phase

  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).

  Screening/baseline, 7 days after each vaccination, and Days 101 and 115 of the challenge period

Secondary Outcomes (2)

• Immunogenicity

  Blood samples drawn at baseline (screening) and Study Days 14, 28, 42, 55/59, 69/73, 86 and 115

• Efficacy - patent parasitemia

  Vaccine recipients are monitored for the development of parasitemia for 28 days post-malaria challenge

Study Arms (4)

Cohort 1 (Low Dose)

EXPERIMENTAL

Ad35.CS.01/Ad26.CS.01 - 1 x 10\^10 vp

Biological: Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp)

Cohort 2 (High Dose)

EXPERIMENTAL

Ad35.CS.01/Ad26.CS.01 - 5 x 10\^10 vp

Biological: Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp)

Cohort 1 - Placebo

PLACEBO COMPARATOR

Biological: Placebo

Cohort 2 - Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp) BIOLOGICAL

Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59).

Cohort 1 (Low Dose)

Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp) BIOLOGICAL

Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59).

Cohort 2 (High Dose)

Placebo BIOLOGICAL

Each placebo subject receives in total three injections of placebo: Day 0, Day 28, and either Day 55 or 59

Cohort 1 - Placebo; Cohort 2 - Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male or non-pregnant female subjects aged ≥18 to ≤50 years on Study Day 0.
• 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.

You may not qualify if:

• 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
• 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.
• History of malignancy, including hematologic and skin cancers (except for a localized basal cell carcinoma).
• History of coagulation defects or bleeding that can not be linked to trauma or surgery.
• History of receiving blood or blood products (such as blood transfusions, platelet transfusion, immunoglobulins, hyperimmune serum) within 6 months prior to Study Day 0.
• History of mental illness as defined by symptoms interfering with social or occupational function or suicidal thoughts / attempts, excluding minor depression resolved or successfully treated at least 3 years prior to Study Day 0.
• Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction to vaccinations.
• History of splenectomy.

Sponsors & Collaborators

• Crucell Holland BV: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator
• Seattle Children's Hospital: collaborator

Study Sites (1)

Malaria Clinical Trials Center at Seattle Biomedical Research Institute

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum; Adenoviridae Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Angela Talley, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 19, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: September 7, 2012

Record last verified: 2012-09

Locations

US (1)