Clinical Trial to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine

NCT04497298 | Completed Phase 1 DMC

• 2 other identifiers: 2020-0162020-002973-89
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a randomized, placebo-controlled, two center, Phase I trial in healthy adult volunteer participants consisting of two phases, an unblinded dose escalation and a double blind treatment phase to investigate the safety, tolerability and immunogenicity of a novel measles-vector based vaccine candidate against SARS-CoV-2 infection (TMV-083/V-591).

Conditions

COVID-19

Keywords

SARS-CoV-2; Vaccine; Prevention

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers

  Rate of solicited Adverse Event up to 14 days after each injection. Rate of unsolicited AE up to 28 days after the last injection. Rate of serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) all along the study period (up to Day 210).

  up to Day 210

Secondary Outcomes (4)

• To assess induction of SARS-CoV-2 spike protein-binding antibodies upon one or two administrations of the COVID-19 vaccine by means of ELISA up to study day 56

  Day 56

• To assess induction of SARS-CoV-2 neutralizing antibodies upon one or two administrations of the COVID-19 vaccine by means of serum neutralization assay up to study day 91

  Day 91

• To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses up to study day 91, induced by one or two doses of vaccine, by means of intracellular staining and flow cytometry.

  up to Day 91

• To assess potential measles virus shedding by means of RT-qPCR of saliva, nasal swab, urine, or blood samples in sentinel groups on day 0 and up to day 42

  up to Day 42

Other Outcomes (3)

• To assess the anti-measles antibody levels at baseline and on day 28 and on day 56 by ELISA

  up to Day 56

• To assess the natural exposure of the subjects to SARS-CoV-2 during the duration of the trial by means of N protein-specific ELISA

  Day 91

• To assess the occurrence of COVID-19 cases in study participants all along the duration of the study

  Day 210

Study Arms (4)

COVID-19 vaccine candidate (TMV-083/V-591) - Low dose

EXPERIMENTAL

Volunteers will receive two administrations of the low dose COVID-19 vaccine candidate by intramuscular (i.m.) injection on day 0 and 28

Biological: Two COVID-19 vaccine candidate (TMV-083/V-591) administrations - Low dose

COVID-19 vaccine candidate (TMV-083/V-591) - High dose

EXPERIMENTAL

Volunteers will receive two administrations of the high dose COVID-19 vaccine candidate by intramuscular (i.m.) injection on day 0 and 28.

Biological: Two COVID-19 vaccine candidate (TMV-083/V-591) administrations - High dose

One COVID-19 vaccine candidate (TMV-083/V-591) - High and placebo

EXPERIMENTAL

Volunteers will receive one administration of the high dose COVID-19 vaccine candidate on day 0 by intramuscular (i.m.) injection and one administration of the placebo on day 28 by intramuscular (i.m.) injection.

Biological: One COVID-19 vaccine candidate (TMV-083/V-591) administration - High dose; Other: Placebo

Placebo

PLACEBO COMPARATOR

Volunteers will receive physiological saline solution (0.9% NaCl), administered by intra muscular (i.m.) injection

Other: Placebo

Interventions

Two COVID-19 vaccine candidate (TMV-083/V-591) administrations - Low dose BIOLOGICAL

Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2)

COVID-19 vaccine candidate (TMV-083/V-591) - Low dose

Two COVID-19 vaccine candidate (TMV-083/V-591) administrations - High dose BIOLOGICAL

Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2)

COVID-19 vaccine candidate (TMV-083/V-591) - High dose

One COVID-19 vaccine candidate (TMV-083/V-591) administration - High dose BIOLOGICAL

Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2) and placebo

One COVID-19 vaccine candidate (TMV-083/V-591) - High and placebo

Placebo OTHER

Physiological saline solution (0.9% NaCl)

One COVID-19 vaccine candidate (TMV-083/V-591) - High and placebo; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females between the ages of 18 and 55 years (at the time of consent).
• Healthy participant, according to the investigator's clinical judgment, as established by medical history, vital signs, physical examination, and laboratory assessments
• Participant with a body mass index (BMI) \<30.0 kg/m2
• Provide written informed consent before initiation of any study procedures.
• A female participant is eligible for this study if she is not pregnant, given by a negative serum pregnancy test at screening and a negative urine pregnancy test at V1 (1st injection), or breast feeding and 1 of the following:
• Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 30 days prior to vaccination up to 6 months after the last injection (D210).
• Highly effective methods of contraception include 1 or more of the following:
• male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant;
• hormonal (oral, intravaginal, transdermal, implantable or injectable);
• an intrauterine hormone-releasing system (IUS);
• an intrauterine device (IUD) with a documented failure rate of \< 1%.
• A female participant is eligible if she is willing to abstain from donating oocyte from the screening visit up to 6 months after the last injection (D210);
• A male participant who is sexually active is eligible if he is willing to :
• use a condom (with/without spermicidal product) from the screening visit up to 6 months after the last injection (D210) except if the male participant is sterile (e.g. vasectomised); the unique female sexual partner is postmenopausal (defined as no menses for 12 months without an alternative medical cause), is permanently sterilized (e.g. hysterectomy or tubal ligation), or use a highly effective methods of contraception;

You may not qualify if:

• Subjects actively or previously infected by SARS-CoV-2, as determined by a positive RT-PCR and positive serology test.
• Subject currently working with high risk of exposure to SARS-CoV-2 (e.g. health care worker, emergency response personnel, etc.) or considered at the investigator's discretion to be at increased risk to acquire SARS-CoV-2 for any other reason.
• Previous vaccination with an investigational COVID-19 vaccine.
• History of presence of pulmonary disorders (e.g. COPD, etc.) or asthma.
• History or present of thrombocytopenia and/or bleeding disorders.
• A positive serum pregnancy test at screening or urine pregnancy test prior to study injection, women who are planning to become pregnant during the study, or women who are breastfeeding.
• Clinically relevant history of or current renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory, autoimmune, central nervous system or neurological diseases or clinically relevant abnormal laboratory values.
• Use of immunosuppressive drugs like e.g. corticosteroids (excluding topical preparations and inhalers) within 3 months prior to the first vaccination or 6 months for chemotherapies and all along the study.
• A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt.
• A history of treatment for any other psychiatric disorder in the past 3 years that increases the risk to the subject in the opinion of the investigator.
• Received immunoglobulin or other blood product within 3 months prior to enrollment or planned receipt of immunoglobulin or a blood product through study completion.
• Vaccination within 4 weeks prior to first injection or planning to receive a licensed vaccine before D56 (e.g. Inactivated influenza vaccine).
• Received measles-containing vaccine within 3 months prior to enrollment.
• History of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as urticaria, respiratory difficulty, angioedema and abdominal pain to vaccines, or history of known or suspected allergic reaction likely to be exacerbated by any component of the COVID-19 vaccine.
• Participation in another investigational clinical study within four weeks before the screening visit or planned before the study completion.

Sponsors & Collaborators

• Institut Pasteur: lead
• Themis Bioscience GmbH: collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator

Study Sites (2)

SGS Life Sciences, Clinical Pharmacology Unit

Antwerp, 2060, Belgium

Location

CIC Cochin - Pasteur

Paris, 75014, France

Location

Related Publications (1)

• Launay O, Artaud C, Lachatre M, Ait-Ahmed M, Klein J, Luong Nguyen LB, Durier C, Jansen B, Tomberger Y, Jolly N, Grossmann A, Tabbal H, Brunet J, Gransagne M, Choucha Z, Batalie D, Delgado A, Mullner M, Tschismarov R, Berghmans PJ, Martin A, Ramsauer K, Escriou N, Gerke C. Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study. EBioMedicine. 2022 Jan;75:103810. doi: 10.1016/j.ebiom.2021.103810. Epub 2022 Jan 16.

  PMID: 35045362 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

Organization and Administration

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Health Services Administration

Study Officials

• Christiane GERKE, PhD

  Institut Pasteur

  STUDY DIRECTOR

• Odile LAUNAY, MD, PhD

  CIC 1417 Cochin-Pasteur

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: As safety precaution, the study will begin with enrollment of two successive unblinded dose groups of sentinel participants randomized into groups of three in an open-label fashion (group A and B). All site personnel, Sponsor and participants will be unblinded. Then remaining participants will be randomized in a blinded manner to one of three cohorts (A, B, C) and between vacccine candidate and placebo. Site personnel responsible for study medication handling, preparation and Administration will be unblinded, only.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 4, 2020
• Study Start: August 10, 2020
• Primary Completion: May 12, 2021
• Study Completion: May 12, 2021
• Last Updated: February 18, 2022

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); BE (1)