Dose-Confirmation, Immunogenicity and Safety Study of the Clostridium Difficile Vaccine Candidate VLA84 in Healthy Adults Aged 50 Years and Older. Phase II Study

NCT02316470 | Completed Phase 2 Results DMC

• 1 other identifier: VLA84-201
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 10

Brief Summary

Phase 2, randomized, observer-blind, placebo-controlled, multi-centric study including 4 parallel study groups. 500 Subjects (thereof, 250 aged 50 - 64 years and 250 aged 65 years and older) will be randomized in a (3:3:3:1) ratio to receive either VLA84 75 µg w/o (without) Alum, VLA84 200 µg w/o Alum, VLA84 200 µg w/ (with) Alum (150 subjects each), or placebo (50 subjects), as i.m. (intramuscular) vaccinations into alternating arms, on Days 0, 7 and 28

Conditions

Clostridium Difficile

Keywords

Clostridium difficile; Valneva; Phase 2; Healthy adults

Outcome Measures

Primary Outcomes (1)

• Seroconversion Rate (SCR) on Day 56

  Seroconversion Rate (SCR), defined as percentage of subjects achieving a ≥4-fold increase in antibody titer from Day 0, for IgG against both Toxin A and Toxin B on Day 56;

  Day 56

Secondary Outcomes (21)

• SCR for IgG (Immunoglobulin G) Against Both Toxin A and Toxin B

  Days 14, 28, 35, 120 and 210

• Seroconversion Rate (SCR) for IgG Against Toxin A

  14, 28, 35, 56, 120 and 210

• Seroconversion Rate (SCR) for IgG Against Toxin B

  Days 14, 28, 35, 56, 120 and 210

• Geometric Mean Titer (GMT) for IgG Against Toxin A

  Days 0, 14, 28, 35, 56, 120 and 210

• Geometric Mean Titer (GMT) for IgG Against Toxin B

  Days 0, 14, 28, 35, 56, 120 and 210

Study Arms (4)

VLA84 75 mcg (microgram) w/o Alum

ACTIVE COMPARATOR

VLA84 75 mcg w/o Alum consists of 0.75 mL (milliliters) VLA84 w/o Alum and 0.75 mL Placebo Vaccination Days: 0, 7 and 28 each with two injections

Biological: VLA84; Biological: Placebo

VLA84 200 mcg w/o Alum

ACTIVE COMPARATOR

VLA84 200 mcg w/o Alum consists of 2 injections each with 1.0 mL (milliliters) VLA84 w/o Alum Vaccination Days: 0, 7 and 28 each with two injections

Biological: VLA84

VLA84 200 mcg with Alum

ACTIVE COMPARATOR

VLA84 200 mcg with Alum consists of 2 injections each with 1.0 mL (milliliters) VLA84 with Alum Vaccination Days: 0, 7 and 28 each with two injections

Biological: VLA84

Placebo

PLACEBO COMPARATOR

Placebo consists of 2 injections each with 1.0 mL PBS (Phosphate Buffered Saline) Vaccination Days: 0, 7 and 28 each with two injections

Biological: Placebo

Interventions

VLA84 BIOLOGICAL

a recombinant fusion protein consisting of truncated Clostridium difficile (C. difficile) Toxin A and Toxin B

VLA84 200 mcg w/o Alum; VLA84 200 mcg with Alum; VLA84 75 mcg (microgram) w/o Alum

Placebo BIOLOGICAL

phosphate buffered saline (PBS) solution

Placebo; VLA84 75 mcg (microgram) w/o Alum

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged ≥50 years of good general health, including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, or type 2 diabetes mellitus.
• Informed consent form has been signed and dated

You may not qualify if:

• Subjects with any confirmed or suspected prior Clostridium difficile infection episode
• Previous vaccination against Clostridium difficile with any (investigational) vaccine or receipt of (investigational) monoclonal antibodies against Clostridium difficile toxins
• Use of any other investigational or non-registered medicinal product within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and throughout the entire study period.
• Active or passive vaccination four weeks before first vaccination at Visit 1 and during the entire study period, except for influenza (seasonal or pandemic) and pneumococcal vaccines which may be administered outside a 7-days interval before and after any trial vaccination
• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile)
• Clinically relevant renal, hepatic, cardiac, pulmonary or central nervous disorders, as judged by the investigator. Subjects with hypercholesterolemia, hypertension, or type 2 diabetes mellitus requiring medication are allowed if disease is adequately controlled
• Receipt of blood or blood-derived products in the past 3 months or anticipation of such products during the study period
• Known congenital, hereditary or acquired immunodeficiency, including known infection with human immunodeficiency virus (HIV), administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 35). For corticosteroids this means prednisone or equivalent ≥ 0.05 mg/kg/day; topical and inhaled steroids are allowed. Periodic steroid injections, e.g., intra-articular, are not allowed within 30 days prior to first VLA84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 35)
• History of autoimmune disease, including Type I Diabetes mellitus. Subjects with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
• Any malignancy in the past 5 years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled
• Known hypersensitivity or allergic reactions to one of the components of the vaccine
• Inability or unwillingness to provide informed consent
• Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities)
• Persons who are in a dependent relationship with the sponsor, an investigator or other study team members, or the study center. Dependent relationships include close relatives and household members (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or study center personnel

Sponsors & Collaborators

• Valneva Austria GmbH: lead

Study Sites (10)

Optimal Research LLC

Huntsville, Alabama, 35802, United States

Location

eStudy Site, Chula Vista

Chula Vista, California, 91911, United States

Location

eStudy Site, La Mesa

La Mesa, California, 91942, United States

Location

eStudy Site, Oceanside

Oceanside, California, 92056, United States

Location

Optimal Research LLC

Melbourne, Florida, 32934, United States

Location

Optimal Research LLC

Peoria, Illinois, 61614, United States

Location

Optimal Research LLC

Mishawaka, Indiana, 46545, United States

Location

Berliner Zentrum für Reise- und Tropenmedizin

Berlin, 10117, Germany

Location

KFGN Klinische Forschung Hannover- Mitte GmbH

Hanover, 30159, Germany

Location

Klinik und Poliklinik für Innere Medizin der Universität Rostock

Rostock, 18057, Germany

Location

Results Point of Contact

• Title: Manager Clinical Research
• Organization: Valneva Austria GmbH

info@valneva.com

+43120620

Study Officials

• Katrin Dubischar

  Valneva Austria GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: December 9, 2014
• First Posted: December 15, 2014
• Study Start: December 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: October 1, 2015
• Last Updated: June 8, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-04

Locations

US (7); DE (3)