A Study to Evaluate the Efficacy and Safety of ZYIL1 Oral Capsules for the Treatment of Patients With Mild to Moderately Active Ulcerative Colitis Resistant or Intolerant to Oral Aminosalicylates

NCT06398808 | Completed Phase 2

• 1 other identifier: ZYIL1.23.001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate efficacy and safety of ZYIL1 oral capsule twice a day for 12 weeks for treatment of mild to moderate active ulcerative colitis resistant or intolerant to oral aminosalicylates.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of ZYIL1 for induction of clinical remission

  clinical remission defined as an mMS score of 0 to 2, including: stool frequency subscore 0 or 1, rectal bleeding subscore 0 and endoscopy score 0 or 1. mMS;modified Mayo Score Minimum value "0" and Maxium Value "9" Higher scores means worse outcome compare to baseline.

  Baseline to week 6

Secondary Outcomes (4)

• Proportion of participants achieving clinical response

  Week 6 and Week 12

• Proportion of participants in clinical remission

  Week 12

• Proportion of participants in endoscopic remission

  Week 6 and Week 12

• Mean change in biomarker fecal calprotectin

  Baseline to Week 6 & Week 12

Study Arms (2)

Arm 1 (ZYIL1 capsules & placebo)

ACTIVE COMPARATOR

ZYIL1 capsules 25 mg for oral administration + 50 mg placebo

Drug: Arm1

Arm 2 (ZYIL1 capsules & placebo)

ACTIVE COMPARATOR

ZYIL1 capsules 50 mg for oral administration + 25 mg placebo

Drug: Arm 2

Interventions

Arm1 DRUG

ZYIL1 capsules 25 mg for oral administration + 50 mg placebo

Arm 1 (ZYIL1 capsules & placebo)

Arm 2 DRUG

ZYIL1 capsules 50 mg for oral administration + 25 mg placebo

Arm 2 (ZYIL1 capsules & placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 18 to 75 years, both inclusive.
• Have had ulcerative colitis (UC) diagnosed at least 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence.
• Mild to Moderate active disease defined as total score of at least 4 on the mMS, endoscopy subscore of at least 2 and a rectal bleeding sub-score of at least 1.
• Demonstrated an inadequate response to, loss of response to, or intolerance to any of the Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide)
• ○ Signs and symptoms of persistently active disease, in the opinion of the investigator, during a current or prior course of at least 4 weeks of treatment with 2.4 g/day mesalamine, 4 g/day sulfasalazine, 1 g/day olsalazine, or 6.75 g/day balsalazide.
• Have undergone colonoscopy within the past 2 years for extent of disease, and if the UC has been present for \> 10 years, have had a colonoscopy with biopsy to rule out dysplasia
• Patients who meet following laboratory values (assessed within 28 days prior to randomization):
• WBCs ≥2000/μL
• Neutrophils ≥1500/μL
• Platelets ≥100 X 10³/μL
• Hemoglobin ≥8.5 g/dL
• Serum creatinine of ≤1.5 X ULN or creatinine clearance \>40 mL/minute (using Cockcroft/Gault formula)
• AST \& ALT ≤1.5 X ULN
• Total bilirubin ≤ 1.5 X ULN
• Men and women of childbearing potential must agree to use adequate birth control measures during the study. Acceptable methods of birth control in this study include: surgical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long acting injectable contraceptive, partner's vasectomy, double-barrier method (condom or diaphragm with spermicide) or abstinence for at least 4 weeks prior to study drug administration, during study participation and for 30 days after their last dose of study drug.

You may not qualify if:

• Diagnosis of Crohn's disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn's disease.
• Have severe extensive colitis as evidenced by at least one of the following:
• Physician judgment that the patient is likely to require colectomy or ileostomy within 12 weeks of baseline.
• Current evidence of fulminant colitis, toxic megacolon or bowel perforation.
• Previous total colectomy
• Have 4 or more of the following i.e Body temperature \> 38 C,HR \> 110 (bpm),Focal severe or rebound abdominal tenderness,Anemia (hemoglobin \[Hgb\] \< 8.5 g/dL), Transverse colon diameter \> 5 cm on plain X-ray.
• Have positive stool culture for pathogens (O P, bacteria) or positive test for C.
• difficile at screening. If C. difficile is positive, the patient may be treated and retested.
• Patients who have an evidence of pathogenic bowel infection.
• History of recurrent or chronic infection (e.g. hepatitis B or C, syphilis, TB).
• Laboratory test positive for HBsAg, HCV or HIV at screening.
• Have had treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 16 weeks of screening.
• History or planned concurrent treatment with biological agents (infliximab, adalimumab, vedolizumab, and ustekinumab), immunosuppressive agents (e.g., azathioprine, 6-MP, or methotrexate) or with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab), Janus kinase (JAK) inhibitor (e.g.,Tofacitininb), steroids (e.g., prednisolone) prior to randomization.
• History of treatment with an investigational agent within 5 half-lives of that agent prior to randomization.
• History of treatment with topical rectal 5-ASA or steroids within 2 weeks of screening.

Sponsors & Collaborators

• Zydus Lifesciences Limited: lead

Study Sites (1)

ICON Hospital

Ahmedabad, Gujarat, 380015, India

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

26S proteasome non-ATPase regulatory subunit 13; DMAC2L protein, human

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Dr. Deven Parmar, MD,FCP

  Zydus Therapeutics Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomly assigned in a 1:1 ratio

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: May 3, 2024
• Study Start: April 8, 2024
• Primary Completion: November 22, 2024
• Study Completion: November 28, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)