Clinical trial NCT02316470: Dose-Confirmation, Immunogenicity and Safety Study of the Clostridium Difficile Vaccine Candidate VLA84 in Healthy Adults Aged 50 Years and Older. Phase II Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile
Keywords: Clostridium difficile
Valneva
Phase 2
Healthy adults
Lead sponsor: Valneva Austria GmbH
Sponsor class: INDUSTRY
First posted: 2014-12-15
Enrollment: 500
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Seroconversion Rate (SCR) on Day 56
timeFrame: Day 56
Secondary outcomes:
measure: SCR for IgG (Immunoglobulin G) Against Both Toxin A and Toxin B
timeFrame: Days 14, 28, 35, 120 and 210
measure: Seroconversion Rate (SCR) for IgG Against Toxin A
timeFrame: 14, 28, 35, 56, 120 and 210
measure: Seroconversion Rate (SCR) for IgG Against Toxin B
timeFrame: Days 14, 28, 35, 56, 120 and 210
measure: Geometric Mean Titer (GMT) for IgG Against Toxin A
timeFrame: Days 0, 14, 28, 35, 56, 120 and 210
measure: Geometric Mean Titer (GMT) for IgG Against Toxin B
timeFrame: Days 0, 14, 28, 35, 56, 120 and 210
measure: GMT for Toxin A Neutralizing Antibodies
timeFrame: Days 0, 35, 56, 120 and 210
measure: GMT for Toxin B Neutralizing Antibodies
timeFrame: Days 0, 35, 56, 120 and 210
measure: SCR for IgG Against Toxin A, Against Toxin B and Against Both Toxin A and Toxin B Stratified by Age Group
timeFrame: Days 14, 28, 35, 56, 120 and 210
measure: GMT for IgG Against Toxin A and Against Toxin B Stratified by Age Group
timeFrame: Days 0, 14, 28, 35, 56, 120, 210
measure: GMTs for Toxin A Neutralizing Antibodies and for Toxin B Neutralizing Antibodies Stratified by Age Group
timeFrame: Days 0, 35, 56, 120 and 210
measure: Responder Rate (RR) for Neutralizing Antibodies Against Both Toxin A and Toxin B
timeFrame: Days 35, 56, 120, 210
measure: Responder Rate (RR) for Toxin A Neutralizing Antibodies
timeFrame: Days 35, 56, 120 and 210
measure: Responder Rate (RR) for Toxin B Neutralizing Antibodies
timeFrame: Days 35, 56, 120 and 210
measure: Responder Rate (RR) for Neutralizing Antibodies Against Toxin A, Against Toxin B and Against Both Toxin A and Toxin B Stratified by Age Group
timeFrame: Days 35, 56, 120 and 210
measure: Rate of Study Participants With at Least One SAE (Serious Adverse Event)
timeFrame: Day 56 and Day 210
measure: Rate of Study Participants With at Least One Related SAE
timeFrame: Day 56 and Day 210
measure: Rate of Study Participants With at Least One Unsolicited AEs (Adverse Event)
timeFrame: Day 56 and Day 210
measure: Rate of Study Participants With at Least One Related Unsolicited AE
timeFrame: Day 56 and Day 210
measure: Rates of Study Participants With at Least One Solicited Local and Systemic AE
timeFrame: within 7 Days after each vaccination
measure: Rates of Study Participants With at Least One SAE, Related SAE, Unsolicited AE and Related Unsolicited AE Stratified by Age Group
timeFrame: Day 56 and Day 210
measure: Rates of Study Participants With at Least One Solicited Local and Systemic AE Within 7 Days After Each and Any Vaccination Stratified by Age Group
timeFrame: within 7 Days after each vaccination
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Optimal Research LLC
state: Alabama
city: Chula Vista
country: United States
facility: eStudy Site, Chula Vista
state: California
city: La Mesa
country: United States
facility: eStudy Site, La Mesa
state: California
city: Oceanside
country: United States
facility: eStudy Site, Oceanside
state: California
city: Melbourne
country: United States
facility: Optimal Research LLC
state: Florida
city: Peoria
country: United States
facility: Optimal Research LLC
state: Illinois
city: Mishawaka
country: United States
facility: Optimal Research LLC
state: Indiana
city: Berlin
country: Germany
facility: Berliner Zentrum für Reise- und Tropenmedizin
city: Hannover
country: Germany
facility: KFGN Klinische Forschung Hannover- Mitte GmbH
city: Rostock
country: Germany
facility: Klinik und Poliklinik für Innere Medizin der Universität Rostock
Study officials:
affiliation: Valneva Austria GmbH
name: Katrin Dubischar
role: STUDY_DIRECTOR
References: