Single Infusion of MK3415A In Patients With C. Difficile Infection

• Research type

  Research Study

• Full title

  A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium difficile toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium difficile toxin A and toxin B) in Patients Receiving Antibiotic Therapy for Clostridium difficile Infection

• IRAS ID

  94900

• Contact name

  Jane Minton

• Sponsor organisation

  Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Eudract number

  2011-004590-90

• Research summary

  C. difficile infection (CDI) is the most common cause of infectious diarrhoea in hospitalised patients in the developed world with increased incidence of recurrent infection. Pathogenic strains of C. difficile produce 2 potent protein toxins, toxin A and/or toxin B. Antibiotic therapy is usually successful in treating the initial episode of CDI; however, approximately 15-30% of these patients will have a recurrent episode. Patients who have experienced at least one episode of recurrent CDI have a 33-60% chance of experiencing additional episodes. A new adjunctive approach to the treatment of CDI is the use of monoclonal antibodies directed against the toxins. Results from the Phase II clinical study of a single infusion of the combination of monoclonal antibodies directed against toxins A and B (MK-3415A) demonstrated a significant difference (p = 0.001) in CDI recurrence between recipients of the monoclonal antibodies (7% [7/101]) and those who received placebo (25% [25/99]). The safety of MK-3415A was comparable to placebo. This is a randomized, double-blind, placebo-controlled, multicentre, Phase III study evaluating the efficacy, safety, and tolerability of monoclonal antibodies to C. difficile exotoxins. Participants receiving standard of care (SOC) therapy will be randomised equally into 1 of 4 treatment groups. On Day 1 participants will receive MK-3415 (toxin A only), MK-6072 (toxin B only), MK-3415A or placebo. The primary efficacy endpoint is the proportion of participants with CDI recurrence through Week 12. Safety will be assessed by the accumulated data on clinical and laboratory adverse experiences in the 4 treatment groups through Week 4. One or both of the individual active treatment groups may be dropped based on the results of a single interim analysis if there is a significant difference in the reduction of CDI recurrence when compared to MK-3415A. An extended follow-up period of 9 months will be conducted in a subset of participants to assess CDI recurrence through Month 12.

• REC name

  North West - Greater Manchester Central Research Ethics Committee

• REC reference

  12/NW/0105

• Date of REC Opinion

  12 Apr 2012

• REC opinion

  Further Information Favourable Opinion