Clinical trial NCT03065374: Treatment for Clostridium-difficile Infection With IMM529
Official title: A Phase I/II, Randomized, Double Blind, Placebo-controlled Clinical Study of IMM529 for the Treatment of Clostridium-difficile Infection (CDI).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Clostridium Difficile Infection
Clostridium Difficile Infection Recurrence
Lead sponsor: Immuron Ltd.
Sponsor class: INDUSTRY
First posted: 2017-02-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events incidence
timeFrame: 12 weeks
measure: Adverse events severity
timeFrame: 12 weeks
Secondary outcomes:
measure: Mortality rate
timeFrame: 0, 7, 14 days and 4, 8, 12 weeks
measure: Disease symptoms incidence
timeFrame: 0, 7, 14 days and 4, 8, 12 weeks
measure: Disease symptoms severity
timeFrame: 0, 7, 14 days and 4, 8, 12 weeks
measure: Recurrence rate
timeFrame: 12 weeks
measure: Recovery rate
timeFrame: 4, 12 weeks
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Hospital
Study officials:
affiliation: Immuron Limited
name: Neta Tobis
role: STUDY_CHAIR
affiliation: Immuron Limited
name: Jerry Kanellos
role: STUDY_CHAIR
References: