Treatment of Mild-moderate Clostridium Difficile Infection (CDI)

NCT04121169 | Unknown Phase 2

• 2 other identifiers: CP-IM-01-2017AHC6-024-C218566
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Patients diagnosed to have mild-moderate CDI will be randomized to receive IM-01 egg-derived anti-C. difficile polyclonal antibodies in increasing dosages, twice daily, for a total of 10 - 14 days. Resolution of diarrhea and other symptoms and fecal test parameters will be used to assess clinical effectiveness of Immunotherapy with IM-01 antibodies. Patients will be followed for recurrence of CDI. Subjects who are assessed as non-respondents to IM-01 will be reassessed and treated with standard of care CDI antibiotics for 10 -14 days.

Conditions

Clostridium Difficile Infection (CDI)

Outcome Measures

Primary Outcomes (2)

• Determine Clinical Response to IM-01 Treatment for CDI for 14 days

  Decrease the frequency of unformed bowel motions to less than 3 per day and sustain for the duration of treatment to 10-14 days.

  10-14 days of IM-01 post-treatment

• Reduce C. difficile pathogen count, spore count, and C. difficile Toxin Titers in stool samples following IM-01 treatment,

  To enumerate numbers of C.difficile present per g of stool by dilution at plate counts on CCFA or Biomerieux C. difficile Chrom Agar , Total counts on three plates express as log 10 count /g versus spore counts after alcohol shock. Toxin titers: expressed as 1/dilution of the fecale filtrate neutralized by specific anti-toxin antibodies from Tech Lab using the CCNA test. .

  day 56 IM-01 post-treatment

Secondary Outcomes (1)

• Rate of recurrence of CDI in day 44, day 56 and day 70 IM-01 post-treatment follow up period

  day 44, 56 and 70 post- IM-01 treatment

Study Arms (2)

Adults subjects with CDI receiving 20g a day

OTHER

10 g twice a day for 10 - 14 days

Drug: IM-01

Adults subjects with CDI receiving 40 g a day

OTHER

20 g twice a day for 10 - 14 days

Drug: IM-01

Interventions

IM-01 DRUG

Antibodies react with C. difficile toxin, C. difficile bacteria and spores; neutralizes the toxin and inhibit the growth of spores and vegetative forms of C. difficile

Also known as: Chicken egg-derived anti-C.difficile polyclonal antibodies

Adults subjects with CDI receiving 20g a day; Adults subjects with CDI receiving 40 g a day

Eligibility Criteria

• Age: 18 Years - 89 Years
• Gender Eligibility Details: Male or Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, aged 18 to 89
• In good general health as evidenced by medical history or Diagnosed with specific condition/disease or Exhibits specific clinical signs or symptoms or physical/oral examination findings
• Participant has a diagnosis of CDI defined as (i) presence of diarrhea with 4 or more unformed stools within 24 hours and (ii) positive test for toxigenic C. difficile from stools collected within 7 days.
• Participants received \< 24 h of SOC therapy for CDI.
• Participants presented with primary CDI episode or any number of CDI relapse recurrence of CDI
• Participants comply with the eligibility criteria and willing to participate in the study including the 8 week post treatment follow up period.
• White Blood Cell absolute neutrophil count \<15 x 109/L,
• Women of reproductive potential must use highly effective contraception. For those with child bearing potential, the following methods of birth control are required from Visit 1 up to at least 30 days after study treatment discontinuation: 1). Diaphragm, female condom or cervical cap, partner's use of a condom, any of which must be used in combination with a spermicide; 2). Intra-uterine device; 3). Oral or injectable contraceptive agent, implant, or transdermal contraceptive hormone patches. If a hormonal contraceptive is used, it must have been taken for at least one month prior to enrolment/randomization; 4). Sterilization method (tubal ligation/occlusion, or partner's vasectomy); 5). True abstinence from intercourse with a male partner only when this is in line with the preferred lifestyle of the subject.
• Men of reproductive potential must use condoms-

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• known allergic reactions to chicken egg components.
• Female of child bearing potential and not receiving contraception; pregnant or lactating persons.
• severe CDI defined as \>10 unformed bowel movements (UBMs)/24 h period, fever \>38.5 o C, White Blood Cell count \> 15 x 109/L, abdominal pain and tenderness on physical examination, toxic megacolon, ileus, nausea, vomiting.
• receipt of \> 24 h of SOC treatment of CDI, or fecal microbial transplant (FMT) prior to enrollment.
• treatment with another investigational drug or other intervention within 30 days prior to enrollment including intravenous immunoglobulin (IVIG) or monoclonal intravenous (IV) antibody.
• received vaccine for C. difficile.
• concurrent use of probiotics of any type during treatment and follow up.
• unable to discontinue use of opiates for diarrhea control.
• co-infection with another gastrointestinal (GI) pathogen.
• presence of Inflammatory Bowel Disease (IBS), IBS with diarrhea (IBS-D), chronic diarrhea of unknown cause.
• any condition that hinders oral consumption. Exception: nasogastric tubes can be used to administer the product.
• death likely within study interval.
• any circumstance or medical condition under the Investigator's opinion that precludes participation.

Sponsors & Collaborators

• ImmuniMed Inc.: lead
• University of Calgary: collaborator
• University of Manitoba: collaborator

Study Sites (1)

Foothills Medical Center

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

Related Publications (1)

• LITERATURE REFERENCES 1. Halsey J. Am. J. Health-Syst Pharm 65: 705-715, 2008. 2. Lessa, F.C et al. N.Eng.J.Med.372: 825-834, 2015. 3. Kee, V. R. Amer. J. Geriatric Pharmacotherapy. 10: 14-24, 2012 4. Centers for Disease Control and Prevention. Vital signs: Making healthcare safer. Stopping C. difficile infections. http:/www.cdc.gov/vitalsigns/Hai/StoppingC.difficile/. March, 2012 5. Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile Infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Miller B.A. et al. Infect Control Hosp Epidemiol. 32:387-390, 2011. 6. (APIC) National Prevalence study for Clostridium difficile in US Healthcare Facilities. November 11, 2008. 7. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Bauer , M.P.; Kuijper, E.J. van Dissel, I.T;. Clin. Microbiol. Infect. 2009, 15: 1067-79. 8. Society for Healthcare Epidemiology of America; Infectious Disease Society of America Clinical Practice guidelines for Clostridium difficile infection in adults: 2010 updates by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Disease Society of America (IDSA). Cohen S.F.; Gerding, D.N.; Johnson, S; et al. Infect. Control Hosp. Epidemiol. 2010, 31: 431-55. 9. Treatment of First recurrence of Clostridium difficile Infection Fidaxomicin Versus Vancomycin. Cornely, O.A; Miller, M.A; Louie, T.J. et al. Clin. Infect. Dis. 2012, 55 (Suppl 2) S154-61. 10. Fidaxomycin versus Vancomycin for C. difficile infections. Louie, T.J; Miller, M.A.; Mullane. D.O et al. New Eng. J. Med. 2011, 364: 422031. 11. Consequence of Clostridium difficile infection: Understanding of healthcare burden. Bouza E. Clin. Microbiol. Infect. 18 (suppl 6) 5-12, Dec 2012. 12. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. He M, Miyajima F, Roberts P et al. Nat. Genet. 45: 109-113, 2012. 13. PCR ribotyping and antimicrobial susceptibility testing of isolates of Clostridium difficile cultured from toxin-positive diarrheal stools of patients receiving medical care in Canadian hospitals: the Canadian Clostridium difficile Surveillance Study (CAN-DIFF) 2013-2015. Karlowsky J. A et al. Diag. Microbiol and Infect Dis. Vol 91. Pages 105-111, 2018 . 14. Antibodies for Treatment of Clostridium difficile Infections. Humphreys, D.P. and Wilcox, M.H. Clinical and Vaccine Immunology 21: 913-923, 2014. 15. Association between antibody response to toxin A and protection against recurrent C. difficile diarrhea. Kyne l et al. Lancet 357: 189-193, 2001. 16. IgG Antibody Response to Toxin A and Toxin B in patients with Clostridium difficile Infection. Wullt M et al. Clin. Vaccine Immunol. 19; 1552-54, 2012. Protocol CP-IM-01-2017A 10 July 2018 (Version 5) ________________________________________________________________________________________________________

  RESULT

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas J Louie, MD,FRCPC

  University of Calgary Foothills Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pradip K Maiti, M.Sc, Ph.D.

CONTACT

204-997-0398; dr.pmaiti@nutratechglobal.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Patients will be randomized 1:1 to receive IM-01 treatment dosage at 20g or 10g twice a day
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Twenty four patients in each group will receive IM-01 treatment at 20g or 10g twice daily:for 10-14 days.

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: October 9, 2019
• Study Start: October 4, 2019
• Primary Completion: December 30, 2023
• Study Completion: March 30, 2024
• Last Updated: December 16, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)