Treatment for Clostridium-difficile Infection With IMM529

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

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

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Infection; Clostridium Difficile Infection Recurrence
• Intervention / Treatment: Other: Placebo; Biological: IMM-529

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Tel HaShomer, Israel
    • Sheba Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Unformed stools (≥3 loose stools in 24 hours at diagnosis)
3. Positive stool testing for C. difficile: PCR and Toxin B positive; or PCR and GDH positive.
4. Up to 3 weeks of diagnosis with at least 20 subjects within 72 hours of diagnosis
5. 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:

1. History of chronic diarrheal illness such as ulcerative colitis or Crohn's disease

2. 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

3. Other etiology of diarrhea.

4. Fulminant CDI, as defined by any of the following attributable to CDI:

   1. Hypotension (Mean arterial pressure < 65mmHg)
   2. Ileus or significant abdominal distention
   3. Toxic megacolon
   4. 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.

5. Severe Clostridium difficile colitis with imminent surgery planned in less than 24 hours.
6. 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.
7. Any active malignancy within the last 5 years apart from localized skin cancer (squamous cell carcinoma or basal cell carcinoma) that was fully excised.
8. 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.
9. Breastfeeding
10. Receipt of other investigational study agent within previous 30 days.
11. Cow milk allergy, lactose intolerance or any known or suspected hypersensitivity to study products
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Immuron Ltd.
• Investigators: Study Chair: Neta Tobis, Immuron Limited; Study Chair: Jerry Kanellos, Immuron Limited

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): November 7, 2019
• Study Completion (Actual): November 7, 2019

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 27, 2017

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Clostridium Infections
• Other Study ID Numbers: IMM592-EP1206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No