Treatment for Clostridium-difficile Infection With IMM529

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of IMM-529 together with standard of care (SOC) in patients with Clostridium-difficile Infection.

Detailed Description
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Subjects who provide voluntary written informed consent will be screened for eligibility. Subjects meeting all of the inclusion and none of the exclusion criteria will be eligible to participate. Eligible subjects will be randomized up to 3 weeks post diagnosis of Clostridium-difficile Infection given SOC initiated already. Each subject will return to the study clinic for assessment and required study procedures on Day 7, Day 14, Week 4, Week 8 and Week 12 post randomization. Treatment duration will be 28 days and follow up will last up to 12 weeks post randomization.

Official Title
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A Phase I/II, Randomized, Double Blind, Placebo-controlled Clinical Study of IMM529 for the Treatment of Clostridium-difficile Infection (CDI).

Conditions
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Clostridium Difficile Infection, Clostridium Difficile Infection Recurrence

Intervention / Treatment
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* Biological: IMM-529
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Unformed stools (≥3 loose stools in 24 hours at diagnosis) Positive stool testing for C. difficile: PCR and Toxin B positive; or PCR and GDH positive. Up to 3 weeks of diagnosis with at least 20 subjects within 72 hours of diagnosis Patient or legal representative must have read, understood, and provided written informed consent after the nature of the study has been fully explained. Exclusion Criteria: History of chronic diarrheal illness such as ulcerative colitis or Crohn's disease Known concurrent severe organ insufficiency: Liver: Decompensated cirrhosis (Any complication of cirrhosis or Child Score ≥7). Cardiovascular: New York Heart Association (NYHA) class IV heart failure, or Ejection fraction <30%. Respiratory: Severe exercise restriction (ie, unable to climb stairs or perform household duties); chronic hypoxia, hypercapnia, severe pulmonary hypertension (>40 mmHg); or respirator dependency Renal: Receiving chronic dialysis or GFR < 15 mL/min/1.73m2 Other etiology of diarrhea. Fulminant CDI, as defined by any of the following attributable to CDI: Hypotension (Mean arterial pressure < 65mmHg) Ileus or significant abdominal distention Toxic megacolon End organ damage/failure: Respiratory - Need for mechanical ventilation. Cardiac - Pulmonary edema. Renal - Serum creatinine increase >3x Baseline, GFR decrease >50%, urinary output <0.5mL/kg/hr > 12hrs. Hepatic - Liver failure (INR>1.5, Hepatic encephalopathy), decompensation of cirrhosis, bilirubin > 2.5mg/dL. Severe Clostridium difficile colitis with imminent surgery planned in less than 24 hours. Immunocompromise due to: immunosuppressants, chemotherapy, radiation in the last 3 months, long-term steroids (>10mg >3 months) or high-dose steroids (>40mg > 3 weeks), leukemia or lymphoma in the last 5 years, or HIV. Any active malignancy within the last 5 years apart from localized skin cancer (squamous cell carcinoma or basal cell carcinoma) that was fully excised. Positive pregnancy test within 24 hours of study infusion or an unwillingness to undergo pregnancy testing in females of child-bearing potential. Females capable of child-bearing must agree not to become pregnant from the time of study enrollment until at least 28 days after completion of study treatment period. If a woman is sexually active and has no history of hysterectomy or tubal ligation, she must agree to use 2 acceptable contraceptives (see section 7.4.1.) while participating in the study and for 28 days following the last dose of study drug. Breastfeeding Receipt of other investigational study agent within previous 30 days. Cow milk allergy, lactose intolerance or any known or suspected hypersensitivity to study products Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely the patient could complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm A<br>IMM-529, 1000 mg three times daily, orally | Biological: IMM-529<br>* IMM-529<br>|
| Placebo Comparator: Treatment arm B<br>Matching Placebo, three times daily, orally | Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events incidence | Number of adverse events | 12 weeks | 
| Adverse events severity | Severity of adverse events | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | Mortality rate | 0, 7, 14 days and 4, 8, 12 weeks | 
| Disease symptoms incidence | Time to resolution of symptoms defined by cessation of unformed stools | 0, 7, 14 days and 4, 8, 12 weeks | 
| Disease symptoms severity | Number of unformed stools per day | 0, 7, 14 days and 4, 8, 12 weeks | 
| Recurrence rate | Rate of subjects with recurring symptoms and positive stool test for C-Diff | 12 weeks | 
| Recovery rate | Stool sampling - neutralizing antibodies and spores and IMM-529 recovery rate | 4, 12 weeks |