An Open-label Study Assessing Safety, Immunogenicity and Dose Response of IC84

NCT01296386 | Completed Phase 1 DMC

• 1 other identifier: IC84-101
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 3

Brief Summary

An open-label Phase 1 Study Assessing the Safety, Immunogenicity and Dose Response of IC84, A new vaccine against Clostridium Difficile (C. difficile), In healthy subjects

Conditions

Clostridium Difficile Infection

Outcome Measures

Primary Outcomes (7)

• Rate of subjects with any SAE (Serious Adverse Event) possibly, probably or certainly related to the study vaccine at any time during the study

  day 201

• Rate of subjects with any unsolicited or solicited Grade 3 or higher adverse event possibly, probably or certainly related to the study vaccine at any time during the study

  day 201

• Rate of subjects with any unsolicited or solicited Grade 3 or higher adverse event possibly, probably or certainly related to the study vaccine during treatment phase (i.e. until Day 28)

  day 201

• Rate of subjects with solicited local AEs (Adverse Events) (injection site pain, tenderness, redness, swelling, induration, itching) within 1 week (Day 0-6) after each vaccination: Severity and duration.

  6 days after vaccination

• Rate of subjects with solicited systemic AEs (headache, muscle pain, fever, flu-like symptoms, nausea, vomiting, rash, excessive fatigue) within 1 week (Day 0 6) after each vaccination: Severity and duration.

  6 days after vaccination

• Rate of subjects with unsolicited non-serious AEs (including safety laboratory parameters (hematology, serum chemistry, urinalysis)) within 6 months after last vaccination: Severity and causality.

  day 201

• Rate of subjects with unsolicited non-serious AEs (including safety laboratory parameters (hematology, serum chemistry, urinalysis) during treatment phase (i.e., until Day 28): Severity and causality.

  day 28

Secondary Outcomes (3)

• Determination of vaccine (IC84) specific IgG levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using an Enzyme-Linked Immunosorbent Assay (ELISA)

  day 201

• Determination of C. difficile Toxin A- and Toxin B-specific IgG levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using an Enzyme-Linked Immunosorbent Assay (ELISA)

  day 201

• Determination of vaccine-induced C. difficile Toxin A- and Toxin B-neutralizing antibody levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using a Toxin Neutralization Assay (TNA)

  day 201

Study Arms (4)

IC84, 75 µg w/ Alum

EXPERIMENTAL

75 µg w/ Alum (microgram with Alum)

Biological: IC84

IC84, 75 µg w/o Alum

EXPERIMENTAL

75 µg w/o Alum (microgram without Alum)

Biological: IC84

IC84, 200 µg w/ Alum

EXPERIMENTAL

200 µg w/ Alum (microgram with Alum)

Biological: IC84

IC84, 200 µg w/o Alum

EXPERIMENTAL

200 µg w/o Alum (microgram without Alum)

Biological: IC84

Interventions

IC84 BIOLOGICAL

IC84, a recombinant fusion protein consisting of truncated Clostridium difficile (C. difficile) Toxin A and Toxin B, which will be administered at two different doses: 75 and 200 µg without or with Al(OH)3, respectively, intramuscular (i.m.) injection, four vaccinations on Day 0, 7, 28 and 56.

IC84, 200 µg w/ Alum; IC84, 200 µg w/o Alum; IC84, 75 µg w/ Alum; IC84, 75 µg w/o Alum

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Healthy adults ≥18 years of age.
• No clinically relevant pathological findings in any of the investigations at the Screening Visit including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, cardiovascular disease or non insulin-dependent diabetes mellitus. Minor deviations of laboratory values from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
• In female subjects, either childbearing potential terminated by surgery or 1 year post menopausal, or a negative serum pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception.
• Weight: ≥ 45.5 kg and \<= 150 kg at Visit 0 (Screening Visit).
• White blood cells ≥2,500/mm3 and \<11,000/mm3 at Visit 0.
• Platelets within normal limits at Visit 0.
• Written informed consent obtained from the subject prior to any study related procedures.

You may not qualify if:

• Use of any other investigational or non-registered medicinal product within 30 days prior to IC84 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.
• Immunodeficiency including status post-organ-transplantation or immuno-suppressive therapy, and a family history of congenital or hereditary immunodeficiency.
• Infection with the human immunodeficiency virus (HIV, a negative test result within 30 days before screening is acceptable), Hepatitis B virus (HBV, Hepatitis B surface antigen \[HBsAg\]) or Hepatitis C virus (HCV).
• History of severe hypersensitivity reactions and anaphylaxis.
• History of allergic bronchial asthma and severe allergic rhinoconjunctivitis.
• Known hypersensitivity or allergic reactions to one of the components of the vaccine.
• 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.
• Clinically significant hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders, which are not adequately controlled by medical treatment within the last 12 weeks before IC84 vaccination at Visit 1 (Day 0) as judged by the site's Principal Investigator.
• Systemic antibiotic use within four weeks prior to first vaccination and during treatment period (until Day 28).
• Clinically significant diseases as judged by the investigator.
• Administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to IC84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 28). (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 IC84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 28).
• Intake of NSAID within three days prior to and within three days after all three vaccinations (Day 0, 7 and 21).

Sponsors & Collaborators

• Valneva Austria GmbH: lead

Study Sites (3)

Privatklinik Leech

Graz, Austria

Location

Medizinische Universität Wien

Vienna, Austria

Location

St. Imre Teaching Hospital

Budapest, Hungary

Location

Related Publications (1)

• Bezay N, Ayad A, Dubischar K, Firbas C, Hochreiter R, Kiermayr S, Kiss I, Pinl F, Jilma B, Westritschnig K. Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers. Vaccine. 2016 May 17;34(23):2585-92. doi: 10.1016/j.vaccine.2016.03.098. Epub 2016 Apr 11.

  PMID: 27079932 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Andrea Ayad, Dr.

  Valneva Austria GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2011
• First Posted: February 15, 2011
• Study Start: December 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 25, 2014

Record last verified: 2014-09

Locations

HU (1); AU (2)