Phase I Study for SynGEM, an Intranasal Respiratory Syncytial Virus (RSV) Prefusion F Subunit Candidate Vaccine

NCT02958540 | Unknown Phase 1 DMC

• 2 other identifiers: MUC-SynGEM-0012015-003814-25
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a double-blind (within dose level), placebo-controlled Phase I study to assess the safety, reactogenicity and tolerability of two intranasal dose levels of SynGEM®: a low dose level (140 μg F-protein/2mg BLPs) and a high dose level ( 350 μg F-protein/5mg BLPs), each administered twice according to a prime-boost schedule 28 days apart at Day 1 and Day 29. The two dose levels will be recruited sequentially. Immunogenicity end-points will include assessment of humoral and cellular responses at selected time-points.

Conditions

Respiratory Syncytial Viral Infections

Keywords

Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability assessed through diaries for local and systemic tolerability and with follow up for occurrence of any adverse event

  subjects' diary

  7 days post each dose / 57 days post prime

Secondary Outcomes (1)

• Immunogenicity responses

  up to 180 day

Study Arms (3)

SynGEM low dose

EXPERIMENTAL

Group 1: 18 subjects receiving SynGEM low dose

Biological: SynGEM

SynGEM high dose

EXPERIMENTAL

Group 2: 18 subjects receiving SynGEM high dose

Biological: SynGEM

placebo

PLACEBO COMPARATOR

12 subjects receiving placebo

Other: placebo

Interventions

SynGEM BIOLOGICAL

Prime / boost vaccination in each group

SynGEM high dose; SynGEM low dose

placebo OTHER

prime /boost vaccination

placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18 - 49 years inclusive.
• Able to give written informed consent to participate.
• Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
• Healthy, as determined by medical history, physical examination, vital signs, and clinical judgment.
• Must have acceptable laboratory parameters\* within 28 days before Day 1. Acceptable laboratory parameters are defined as follows:
• A. Hemoglobin, Red Blood Cell (RBC) count and hematocrit: within laboratory normal sex-specific range.
• B. White Blood Cell (WBC) count within the normal laboratory range C. Sodium and potassium within laboratory normal range D. Total bilirubin within laboratory normal range E. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST): ≤1.1x institutional ULN.
• F. Serum creatinine: ≤1.1x institutional upper limit of normal (ULN).
• \*Note: If the acceptable laboratory screening parameters listed above are out of the above defined range, repeat of screening tests is permitted once, provided there is an alternative explanation for the out-of-range value. Out of range results for laboratory tests either listed or not in Section 8.6.3 other than those covered in the list above are acceptable if considered not clinically significant by the Investigator.
• A Body Mass Index (BMI) between 18 and 32, inclusive. BMI = weight (kg)/height2 (m2).
• Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test within 24 hours preceding receipt of each dose and agree to practice, if not already practicing, highly effective birth control measures from 28 days before the prime vaccination until at least 90 days after the boost vaccination. For women already practicing highly effective birth control measurements for at least 28 days at screening start, recruitment can occur as soon as all screening procedures are completed. The following birth control measure will be considered highly effective:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner (if the partner is the sole sexual partner and has received medical assessment of the surgical success).
• True abstinence: when this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception\].
• If not heterosexually active at screening, must agree to practice highly effective birth control measures described above if they become heterosexually active from that moment onwards until at least 90 days after the boost vaccination.
• Agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction from the start of screening onwards until at least 90 days after the boost vaccination.

You may not qualify if:

• History of acute respiratory disease in the 30 days preceding start of screening or documented infection with RSV in the previous 3 months.
• Any chronic disease of the nasal cavity such as chronic hypertrophic or atrophic rhinitis, chronic sinusitis, ozena, Wegener's granulomatosis or granulomatosis with polyangiitis.
• History of asthma or chronic obstructive pulmonary disease.
• Presence of significant uncontrolled medical or psychiatric illness (acute or chronic). This includes institution of a new medical or surgical treatment, or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening.
• Subjects who are positive for hepatitis B surface antigen, hepatitis C antibodies or HIV.
• Pregnant or breastfeeding women, or planning to become pregnant while enrolled in the study or within 90 days after the boost vaccination.
• Cancer, or treatment for cancer, within 3 years, excluding basal cell carcinoma or squamous cell carcinoma of the skin, which is allowed.
• Presence of any medical condition that may be associated with impaired immune responsiveness, including diabetes mellitus.
• Presently receiving or history of receiving, during the preceding 3-month period, any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulins, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Topical corticosteroids are allowed.
• Receipt of any intranasal administration of drug or vaccine within the 30 days prior to the first administration of study vaccine or plans to receive any intranasal administration of drug or vaccine until the end of study visit.
• Receipt of live attenuated vaccine within 30 days of first SynGEM® administration or plans to receive within 30 days after the last study vaccine administration, and receipt of any other vaccine within 15 days of first SynGEM® administration or plans to receive within 15 days after the last study vaccine administration.
• Positive history of illicit drug use, of drug or alcohol abuse within the previous 6 months.
• History of anaphylactic type reaction to injected vaccines.
• History of allergic rhinitis or of allergy to food.
• History of allergy to insect bites, latex, pollens, house dust mites that are considered significant by the Investigator.

Sponsors & Collaborators

• Mucosis BV: lead
• Imperial College London: collaborator

Study Sites (1)

Imperial Centre for Translational and Experimental Medicine Hammersmith Hospital

London, United Kingdom

Location

Related Publications (1)

• Ascough S, Vlachantoni I, Kalyan M, Haijema BJ, Wallin-Weber S, Dijkstra-Tiekstra M, Ahmed MS, van Roosmalen M, Grimaldi R, Zhang Q, Leenhouts K, Openshaw PJ, Chiu C. Local and Systemic Immunity against Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A Randomized, Double-Blind, Placebo-controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Aug 15;200(4):481-492. doi: 10.1164/rccm.201810-1921OC.

  PMID: 30753101 DERIVED

Study Officials

• Chris Chiu, PhD, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2016
• First Posted: November 8, 2016
• Study Start: October 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 8, 2017

Record last verified: 2017-09

Locations

GB (1)