Phase 1 Study to Evaluate the Safety and Immunogenicity of a Candidate Vaccine Against Respiratory Syncytial Virus

NCT04519073 | Completed Phase 1 DMC

• 1 other identifier: VMXRSV306-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The primary and secondary objectives of this Phase 1 study are respectively to assess the safety and the immunogenicity of two administrations of the RSV vaccine candidate at three different doses. The study has a randomized, placebo-controlled, double-blind, sequential, parallel cohorts, dose-escalation (three dosages) design. Each of the three cohorts (N=20 subjects per cohort, total of 60 subjects) will receive placebo (n=5), or a low (15 µg, n=15), intermediate (50 µg, n=15) or high dosage (150 µg, n=15) of candidate vaccine, on two occasions (Day 0 and Day 56). Subjects will be healthy adult women aged between 18 and 45 years. There will be two phases: an active treatment phase from Day 0 to Month 3, and a follow-up phase from Month 3 + 1 day to Month 12. During the active phase, subjects will complete diary cards to record oral temperature (daily), solicited local and general adverse events (AEs) and unsolicited AEs for 7 days after each administration. Unsolicited AEs will be recorded up to Day 28 post-each administration. Serious adverse events (SAEs) and adverse events of specific interest (AESI) will be recorded throughout the duration of the active phase. Subjects will visit the clinical site for safety monitoring on Days 1, 7 and 28 following each administration. Blood will be drawn at a screening visit and the safety test data will be available just before 1st administration. The screening set includes markers of infection with hepatitis B virus, hepatitis C virus and human immunodeficiency virus. A serum sample will be taken for detection of pregnancy. At the next scheduled time points, pregnancy will be screened in a urine sample. Laboratory safety parameters will be examined further at Days 0, 1, 7, 28, 56, 57, 63 and 84. During the follow-up phase, visits for safety monitoring are scheduled at Months 6, 9 and 12 post-1st administration. SAEs and AESI will be recorded at each visit. Humoral immunity will be measured on Days 0, 28, 56, Month 3, Month 6, Month 9 and Month 12. Cellular immunity will be measured on Days 0, 7, 28, 56, 63 and 84. The duration of the study for each subject will be approximately 13 months. The total duration of the study will be approximately 18 months.

Conditions

Acute Bronchiolitis Due to Respiratory Syncytial Virus

Outcome Measures

Primary Outcomes (3)

• Solicited local and general adverse events

  Number and percentage of subjects reporting solicited local and general AEs reported on diary card during 7 days post-each administration in the placebo group and in the three vaccine cohorts. Local solicited symptoms are pain, induration, erythema, and swelling at administration site. General solicited symptoms are headache, fatigue, body temperature (measured orally) and generalized myalgia.

  During 7 days post-each administration

• Adverse events of special interest (AESI)

  Number and percentage of subjects reporting AESI in the placebo group and in the three vaccine cohorts. Monitoring of AESI will include lower respiratory tract infection (LRTI) and respiratory events such as dyspnoea, wheezing, cough, other asthmatic symptoms and increased sputum production.

  Day 0 to Month 12

• Serious adverse events

  Number and percentage of subjects reporting serious adverse events in the placebo group and in the three vaccine cohorts.

  Day 0 to Month 12

Secondary Outcomes (1)

• Humoral immune response

  Day 0 to Month 12

Study Arms (4)

Placebo

PLACEBO COMPARATOR

0.5 mL of diluent (phosphate buffer)

Biological: V-306 candidate vaccine

V-306 low dose

EXPERIMENTAL

V-306 at 15 µg

Biological: V-306 candidate vaccine

V-306 intermediate dose

EXPERIMENTAL

V-306 at 50 µg

Biological: V-306 candidate vaccine

V-306 high dose

EXPERIMENTAL

V-306 at 150 µg

Biological: V-306 candidate vaccine

Interventions

V-306 candidate vaccine BIOLOGICAL

Each V-306 monomer consists of the following elements: 1. A Lipopeptide Building Block that contains an optimized, artificially designed coiled-coil domain, which self-assembles into highly stable trimers. 2. A 'universal' T-helper epitope fused at the C-terminus of the coiled-coil domain. 3. A lipid component di-palmitoyl-S-glyceryl cysteine (Pam2C), fused at the N-terminus. 4. A mimetic of the Palivizumab epitope, referred to RSV F-protein site II antigen mimetic (FsIIm), which is coupled near the C-terminus of the Lipopeptide Building Block via a short maleimide-PEG-oxime linker.

Placebo; V-306 high dose; V-306 intermediate dose; V-306 low dose

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Healthy women aged between 18-45 years.
• No evidence of disease based on medical history, physical examination, vital signs (blood pressure, heart rate, body temperature and respiratory rate), laboratory safety parameters and clinical judgement.
• Not pregnant and committed to not becoming pregnant during the whole study period. Committed to use adequate and effective contraception means in accordance with the Clinical Trial Facilitation Group (CTFG) criteria.
• The subjects must have used adequate and effective contraception means (CTFG criteria) for at least 60 days prior to the 1st administration.
• Capability to meet the requirements of the study.

You may not qualify if:

• Presence of serologic markers of acute or chronic Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBsAg and anti-HBc) and Hepatitis C Virus (anti-HCV) infection(s).
• As judged by the Investigator, any clinically significant disease related to the cardiovascular (CV), gastrointestinal (GI) or central nervous system (CNS).
• Any chronic disease, or history of significant disease that might interfere with the trial's conduct or completion. Some conditions may be accepted if stabilised, e.g. hypertension.
• An active respiratory disease or symptoms thereof (chronic obstructive pulmonary disease, asthma, asthmatic bronchitis, dyspnoea, wheezing, severe allergy) requiring medication, or history of such disease.
• Personal history of active or past autoimmune disease
• Administration for more than three months prior of study start of immunosuppressant or immuno-modifying drugs (including systemic corticosteroids).
• Confirmed or suspected (at the discretion of the Investigator) immuno-suppressive or immuno-deficient condition.
• Current smokers (more than 10 cigarettes/day).
• Blood transfusion, blood product, immunoglobulins received during the period of 3 months prior to study start.
• Clinically significant (according to Investigator's judgement) laboratory out of range values. The abnormal lab test can be neglected if its cause is evident and of no clinical relevance
• Acute disease and/or fever (≥38°C measured by the oral route) at the time of test article administration. Vaccine administration can be postponed until the febrile episode is over.
• Recent vaccination (e.g., vaccine administration within 2 weeks or 4 weeks \[live attenuated\]) or evidence that a vaccine will be required during the study period (e.g., planned travel).
• Pregnant or plan to become pregnant during the study period.
• Breastfeeding.
• Women highly exposed to children less than 5 years of age will be excluded to reduce risk of RSV infection, including mothers of young children, paediatric nurses, personnel of day nursery.

Sponsors & Collaborators

• Virometix: lead
• Center of Vaccinology, Ghent, Belgium (CEVAC): collaborator
• Expert Clinical Services Organization, Brussels, Belgium (ECSOR): collaborator

Study Sites (1)

Centre for Vaccinology (CEVAC)

Ghent, 9000, Belgium

Location

Study Officials

• Anna Sumeray, MD

  Virometix

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Investigator, the laboratory and the subjects will be kept blind to the treatment arm (placebo/vaccine) to which the subject has been allocated up to the end of the study (Month 12).
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blind, sequential, parallel cohorts, dose-escalation (three dosages) study in one centre.

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 19, 2020
• Study Start: September 7, 2020
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: March 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)