A Randomized, Observer-Blinded, Dose-Escalation Phase 1 Study to Assess the Safety and Immunogenicity of Three Different Dose Levels of a Live-Attenuated Chikungunya Virus Vaccine Candidate (VLA1553) in Healthy Volunteers Aged 18 To 45 Years
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Chikungunya
- Sponsor
- Valneva Austria GmbH
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Frequency of solicited systemic reactions
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Randomized, observer-blinded, multicenter, dose-escalation Phase 1 clinical study investigating three dose levels of VLA1553 after a single immunization.
120 study participants will be enrolled into the study to receive three different doses (30 subjects in the low and medium and 60 subjects in the high dose group). Vaccination will be given intramuscularly on Day 0. As safety precaution, the study will begin with enrolment of 20 sentinel subjects in an open-label fashion. Thereafter, subjects will be enrolled in a blinded, randomized manner in the three study arms.
A re-vaccination will be given at Month 6 or Month 12 to confirm that a single vaccination will be sufficient to induce high titer neutralizing antibodies and protect subjects from CHIKV viremia.
Study participants will be followed up until 13 months after initial vaccination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged 18 to 45 years on the Day of screening;
- •Has a BMI of ≥ 18.5 and \< 30 kg/m2 on the Day of screening;
- •Understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to any study-related procedures;
- •Generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests;
- •If female, subject is of non-childbearing potential. The definition of non-childbearing potential includes the following:
- •Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian tube ligation; endometrial ablation), at least 30 days prior to signature of the Informed Consent form;
- •At least 5 years post-menopause (i.e., 6 years post last menstrual period), or menopause confirmed by follicle-stimulating hormone (FSH) testing.
Exclusion Criteria
- •History of known CHIKV infection;
- •Plans to travel to areas with active CHIKV transmission during the course of the study or history of travel to an endemic CHIKV area within 4 weeks prior to study enrollment;
- •Participation in a clinical study involving an investigational CHIKV vaccine;
- •Receipt of an inactivated vaccine within 4 weeks or live vaccine within 8 weeks prior to vaccination in this study;
- •Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);
- •(1) Abnormal laboratory liver function values (≥ grade 1), (2) any grade 1 abnormal lab values deemed clinically relevant by the Investigator, and (3) any ≥ grade 2 abnormal lab values irrespective of clinical significance at screening;
- •Clinically significant abnormal ECG at screening;
- •History of significant cardiovascular, respiratory (including asthma), metabolic, neurological, hepatic, rheumatic, autoimmune, hematological, gastrointestinal or renal disorder;
- •History of immune-mediated or clinically significant arthritis/arthralgia;
- •History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved a cure;
Outcomes
Primary Outcomes
Frequency of solicited systemic reactions
Time Frame: up to Day 14 after single vaccination
Systemic reactions including fever, nausea/vomiting, headache, fatigue, myalgia (muscle pain), arthralgia (joint pain) and rash will be reported in a standardized manner
Severity of solicited injection site reactions
Time Frame: up to Day 14 after single vaccination
Any measurable injection site reaction will be measured by size and includes injection site pain, tenderness, erythema/redness, induration and swelling. They will be rated according to the Severity Grading Scale of Injection Site Reactions (FDA Guidance on Toxicity Grading Scales for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007)
Frequency of solicited injection site reactions
Time Frame: up to Day 14 after single vaccination
Any measurable injection site reaction will be measured by size and includes injection site pain, tenderness, erythema/redness, induration and swelling.
Severity of solicited systemic reactions
Time Frame: up to Day 14 after single vaccination
Systemic reactions including fever, nausea/vomiting, headache, fatigue, myalgia (muscle pain), arthralgia (joint pain) and rash will be reported in a standardized manner. They will be rated according to the FDA Guidance on Toxicity Grading Scales
Secondary Outcomes
- Severity of solicited injection site reactions(until Day 14, Day 28 and throughout the study period)
- Frequency of solicited systemic reactions(until Day 14, Day 28 and throughout the study period)
- Assessment of viremia after each vaccination(on Days 3, 7, 14 and beyond Day 14 after re-vaccination)
- Frequency of any adverse event (AE)(until Day 14, Day 28 and throughout the study period)
- Frequency of solicited injection site reactions(until Day 14, Day 28 and throughout the study period)
- Immune response as measured by CHIKV-specific neutralizing antibody titer as determined by micro-neutralization (μNT) assay.(Day 28, Day 84, Month 6, Month 12, and 28 days after re-vaccination)
- Severity of any adverse event (AE)(until Day 14, Day 28 and throughout the study period)
- Severity of solicited systemic reactions(until Day 14, Day 28 and throughout the study period)