Weekly CLF065 injections for chronic pouchitis

A Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of CLF065 in the Treatment of Chronic Pouchitis

This trial will test whether weekly injections of CLF065 can reduce inflammation and symptoms in adults with recurrent chronic pouchitis.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Calibr, a division of Scripps Research (other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT07226050 on ClinicalTrials.gov

What this trial studies

Adults with recurrent chronic pouchitis will receive once-weekly subcutaneous injections of long-acting GLP-2 (CLF065) or placebo during the first 13 weeks of a 24-week study period. Some injections will be given at the study site and other doses will be self-administered at home. Participants will keep a daily bowel diary and complete questionnaires about living with chronic pouchitis to track symptoms and quality of life. The goals are to establish the safety, feasibility, and efficacy of weekly CLF065 dosing compared with placebo.

Who should consider this trial

Good fit: Adults aged 18–80 with a confirmed diagnosis of recurrent chronic pouchitis after IPAA, a baseline mPDAI average ≥5 and endoscopic subscore ≥2, and either ≥3 antibiotic-treated episodes in the prior year or ongoing maintenance antibiotic use are ideal candidates.

Not a fit: Patients without confirmed chronic pouchitis, those less than one year from IPAA, those with alternative causes of symptoms, or those with contraindications to GLP-2 therapy may not receive benefit.

Why it matters

Potential benefit: If successful, CLF065 could reduce pouch inflammation and symptoms and improve quality of life with a once-weekly injection.

How similar studies have performed: GLP-2 analogs have shown clinical benefit in conditions like short bowel syndrome, but applying a long-acting GLP-2 to pouchitis is relatively novel with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Adult subjects aged 18-80 years, inclusive.
2. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
3. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
4. Diagnosis of pouchitis that is recurrent, defined by mPDAI score of ≥ 5 assessed as the average from 3 days immediately prior to Baseline endoscopy, and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either:

   ≥ 3 episodes of pouchitis within 1 year of Screening visit, each treated with antibiotic or other prescription therapy for at least 2 weeks OR Requiring maintenance antibiotic therapy taken continuously for ≥ 4 weeks immediately prior to the Baseline endoscopic visit
5. The patient has a history of proctocolectomy and construction of an IPAA for ulcerative colitis at least one year before the Screening Visit.
6. The patient agrees to stop antibiotic therapy.
7. Patient agrees to taper any corticosteroid or budesonide starting by Week 4 of the study per guidelines below.
8. A male subject who is nonsterilized and sexually activity with a female partner of childbearing potential agrees to use a barrier method of contraception (e.g., condom with spermicide) from signing informed consent throughout the duration of the study.
9. Women of childbearing potential must not have a positive pregnancy test at the Screening Visit and must have a negative pregnancy test at the baseline visit prior to study drug dosing. Note: subjects with borderline serum pregnancy test at Screening must have an absence of clinical suspicion of pregnancy or other pathological cause of a borderline result and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result.
10. If female, the patient must be either postmenopausal, OR permanently surgically sterile or for women of childbearing potential practicing at least one protocol specified method of birth control, that is effective from baseline visit through at least 30 days after the last dose of study drug.
11. Patient is judged to be in good health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination

Exclusion Criteria:

1. Inability to give informed consent.
2. The patient has received any investigational product or approved biologic or biosimilar agent within 60 days of 5 half-lives of randomization (whichever is longer)
3. No prior exposure to CLF065
4. Chronic pouchitis specific:

   1. The patient has received 6-MP, Azathioprine or methotrexate within 4 weeks of the Screening Visit
   2. Crohn's disease with disease proximal to the pouch inlet confirmed on prior imaging or endoscopy
   3. Irritable pouch syndrome
   4. Predominate or isolated cuffitis
   5. Mechanical complications of the pouch
   6. Diverting stoma
   7. Planned surgical intervention of the pouch
5. History of malignancy including melanoma (with the exception of localized skin cancers, carcinoma in situ of the cervix and localized prostate cancer) within 2 years of study enrollment
6. Pregnant or breast feeding.
7. Lack of effective contraception in women of childbearing potential.
8. Ongoing treatment with NSAID (nonsteroidal anti-inflammatory drug).
9. Anastomotic or anal canal stricture which precludes endoscopic evaluation.
10. The patient has evidence of pelvic sepsis and pelvic penetrating fistulizing disease on clinical exam.
11. Known diagnosis of primary sclerosing cholangitis.
12. Fecal transplantation within 12 weeks prior to study enrollment.
13. History of clinically significant medical conditions or any other reason that in the opinion of the investigator would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug or would put the subject at risk by participating in the study.
14. The patient has any of the following laboratory abnormalities during the Screening Period:

    1. Hemoglobin level \<8 g/dL
    2. White blood cell (WBC) count \<3 x 109/L
    3. Platelet count \<100 x 109/L or \>1200 x 109/L
    4. Serum creatinine \>2 x ULN
    5. Alanine aminotransferase (ALT) or aspartate aminiotransferase (AST) \>2x ULN
    6. Alkaline phosphatase \>2 x ULN

Where this trial is running

Los Angeles, California

• Phillip Fleshner, M.D. Inc — Los Angeles, California, United States (RECRUITING)

Study contacts

• Study coordinator: Amy Camblos

Conditions: Pouchitis, chronic pouchitis