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

Clostridium Difficile Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02316470
• Other study ID #: VLA84-201
• Status: Completed
• Phase: Phase 2
• First received: December 9, 2014
• Last updated: October 27, 2015
• Start date: December 2014
• Est. completion date: October 2015

Study information

• Verified date: October 2015
• Source: Valneva Austria GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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

Description:

This is a randomized, controlled, observer-blind Phase 2 study which aims to confirm the optimal dose and formulation of VLA84 in healthy adults aged ≥ 50 years of age. The study will be enrolled in two age strata, subjects aged 50 - 64 years and subjects aged 65 years and older, in a 1:1 ratio.

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 Alum, VLA84 200 µg w/o Alum, VLA84 200 µg w/ Alum (150 subjects each), or placebo (50 subjects). Vaccinations consist of two i.m. injections administered in close proximity to each other in the deltoid region at Day 0, 7 and 28, starting with the non-dominant arm and alternating arms between the vaccination days.

The study will investigate the immunogenicity and safety of VLA84 up to six months after the last vaccination, i.e. 210 days per subject. The study includes eight outpatient visits on days 0, 7, 14, 28, 35, 56, 120 and 210. Serum will be collected to assess humoral immunity at days 0, 7, 14, 28, 35, 56, 120 and 210.

The study is OBSERVER blind. This means only pre-defined study staff will be unblinded, e.g., staff responsible for IMP accountability, preparation and administration, monitor responsible IMP accountability, or safety staff in case of safety reasons. All other persons involved in study conduct will remain blinded.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: October 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• Known thrombocytopenia, bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion or until Visit 4 (Day28), contraindicating i.m. vaccination as judged by the investigator

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Clostridium Difficile

Intervention

Biological:
• VLA84
a recombinant fusion protein consisting of truncated Clostridium difficile (C. difficile) Toxin A and Toxin B
• Placebo
phosphate buffered saline (PBS) solution

Locations

Country	Name	City	State
Germany	Berliner Zentrum für Reise- und Tropenmedizin	Berlin
Germany	KFGN Klinische Forschung Hannover- Mitte GmbH	Hannover
Germany	Klinik und Poliklinik für Innere Medizin der Universität Rostock	Rostock
United States	eStudy Site, Chula Vista	Chula Vista	California
United States	Optimal Research LLC	Huntsville	Alabama
United States	eStudy Site, La Mesa	La Mesa	California
United States	Optimal Research LLC	Melbourne	Florida
United States	Optimal Research LLC	Mishawaka	Indiana
United States	eStudy Site, Oceanside	Oceanside	California
United States	Optimal Research LLC	Peoria	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Valneva Austria GmbH

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seroconversion Rate (SCR) on Day 56	Seroconversion Rate (SCR, defined as proportion 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	No
Secondary	SCR for IgG (Immunoglobulin G) against both Toxin A and Toxin B		Days 0, 14, 28, 35, 120 and 210	No
Secondary	SCR for IgG against Toxin		0, 14, 28, 35, 56, 120 and 210	No
Secondary	SCR for IgG against Toxin B		Days 0, 14, 28, 35, 56, 120 and 210	No
Secondary	Geometric Mean Titer (GMT) for IgG against Toxin A	Geometric Mean Titer (GMT) for IgG against Toxin A as determined by ELISA on Days 0, 14, 28, 35, 56, 120 and 210	Days 0, 14, 28, 35, 56, 120 and 210	No
Secondary	Geometric Mean Titer (GMT) for IgG against Toxin B	Geometric Mean Titer (GMT) for IgG against Toxin B as determined by ELISA on Days 0, 14, 28, 35, 56, 120 and 210	Days 0, 14, 28, 35, 56, 120 and 210	No
Secondary	Responder Rate for neutralizing antibodies against both Toxin A and Toxin B	Responder Rate (defined as proportion of subjects achieving a =4-fold increase in neutralizing antibody titer from Day 0) for neutralizing antibodies against both Toxin A and Toxin B on Days 0, 35, 56, 120 and 210	Days 0, 35, 56, 120	No
Secondary	Responder Rate for Toxin A neutralizing antibodies		Days 0, 35, 56, 120 and 210	No
Secondary	Responder Rate for Toxin B neutralizing antibodies		Days 0, 35, 56, 120 and 210	No
Secondary	GMT for Toxin A neutralizing antibodies	GMT for Toxin A neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120 and 210	Days 0, 35, 56, 120 and 210	No
Secondary	GMT for Toxin B neutralizing antibodies	GMT for Toxin B neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120 and 210	Days 0, 35, 56, 120 and 210	No
Secondary	SCR for IgG against Toxin A, against Toxin B and against both Toxin A and Toxin B	SCR for IgG against Toxin A, against Toxin B and against both Toxin A and Toxin B on Days 0, 14, 28, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)	Days 0, 14, 28, 35, 56, 120 and 210	No
Secondary	GMT for IgG against Toxin A and against Toxin B	GMT for IgG against Toxin A and against Toxin B on Days 0, 14, 28, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)	Days 0, 14, 28, 35, 56, 120	No
Secondary	Responder Rate for neutralizing antibodies against Toxin A, against Toxin B and against both Toxin A and Toxin B	Responder Rate for neutralizing antibodies against Toxin A, against Toxin B and against both Toxin A and Toxin B on Days 0, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)	Days 0, 35, 56, 120 and 210	No
Secondary	GMTs for Toxin A neutralizing antibodies and for Toxin B neutralizing antibodies	GMTs for Toxin A neutralizing antibodies and for Toxin B neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)	Days 0, 35, 56, 120 and 210	No
Secondary	Rate of SAEs (Serious Adverse Event)		Day 56 and Day 210	Yes
Secondary	Rate of related SAEs		Day 56 and Day 210	Yes
Secondary	Rate of unsolicited AEs (Adverse Event)	Rate of unsolicited AEs to Day 56 and Day 210 (incl. clinically significant laboratory parameter changes)	Day 56 and Day 210	Yes
Secondary	Rates of related unsolicited AEs	Rates of related unsolicited AEs to Day 56 and Day 210 (incl. clinically significant laboratory parameter changes)	Day 56 and Day 210	Yes
Secondary	Rates of solicited local and systemic AEs	Rates of solicited local and systemic AEs within 7 days after each and after any vaccination	within 7 Days after each vaccination	Yes
Secondary	Rates of SAEs, related SAEs, unsolicited AEs	Rates of SAEs, related SAEs, unsolicited AEs (incl. clinically significant laboratory parameter changes) and related unsolicited AEs, to Day 56 and Day 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)	Day 56 and Day 210	Yes
Secondary	Rates of solicited local and systemic AEs	Rates of solicited local and systemic AEs within 7 days after each and after any vaccination, stratified by age group (subjects 50 - < 65 years and 65 years and older)	within 7 Days after each vaccination	Yes