Comparison of Ustekinumab, Infliximab and Combination Therapy in Moderately to Severely Active Ulcerative Colitis

NCT06453317 | Recruiting Phase 2 DMC

• 2 other identifiers: Combo/2022/32023-506452-25
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if combined therapy with infliximab and ustekinumab works better than using these drugs alone in adult patients with ulcerative colitis. It will also learn about the safety of this combination. The main questions it aims to answer are: Does the combination therapy improve the symptoms and heal the intestine quicker and better than these drugs administered alone? Does the combination therapy improve the quality of life better than these drugs administered alone? What medical problems do participants have when taking the combination therapy? Participants: Patients diagnosed with UC will be qualified to biologic therapy (infliximab/ustekinumab/infliximab + ustekinumab). Visit the clinic in stated periods for assessment and to apply medication. Take drugs based on the schedule.

Conditions

Ulcerative Colitis; Inflammatory Bowel Diseases

Keywords

dual biological therapy; infliximab; ustekinumab; Inflammatory Bowel Diseases; Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with clinical and endoscopic remission after the induction phase.

  Clinical remission: PRO-2 score ≤1 points, total Mayo score \<3 Endoscopic remission: endoscopic Mayo score ≤1

  Week 14 for Infliximab arm and Week 16 for Ustekinumab and Infliximab + Ustekinumab arms

Secondary Outcomes (8)

• Percentage of patients with clinical response after the induction phase.

  Week 14 for Infliximab arm and Week 16 for Ustekinumab and Infliximab + Ustekinumab arms

• Percentage of patients with clinical response at Week 52.

  Week 52

• Percentage of patients with clinical remission at Week 52.

  Week 52

• Percentage of patients with endoscopic response or remission after the induction phase and at Week 52

  Week 14 for Infliximab arm and Week 16 for Ustekinumab and Infliximab + Ustekinumab arms and Week 52

• Percentage of patients with biochemical remission after the induction phase and at Week 52.

  Week 14 for Infliximab arm and Week 16 for Ustekinumab and Infliximab + Ustekinumab arms and Week 52

Study Arms (3)

Infliximab

ACTIVE COMPARATOR

Infliximab 5 mg/kg i.v at Weeks 0, 2, 6 and then every 8 weeks for 52 weeks.

Biological: Infliximab

Ustekinumab

ACTIVE COMPARATOR

Ustekinumab: first dose i.v. at Week 0 (Patients with body weight ≤55 kg - 260 mg, patients with body weight \>55-≤85 kg 390 mg, patients with body weight \>85 kg - 520 mg) then 90 mg s.c. every 8/12 weeks for 52 weeks.

Biological: Ustekinumab

Infliximab + Ustekinumab

EXPERIMENTAL

Infliximab 5 mg/kg i.v. at Week 0, 2, 6. \+ Ustekinumab: first dose i.v. at Week 0 (Patients with body weight ≤55 kg - 260 mg, patients with body weight \>55-≤85 kg 390 mg, patients with body weight \>85 kg - 520 mg) then 90 mg s.c. every 8/12 weeks for 52 weeks

Biological: Infliximab; Biological: Ustekinumab

Interventions

Infliximab BIOLOGICAL

Infliximab 5 mg/kg i.v at Weeks 0, 2, 6 and then every 8 weeks for 52 weeks.

Infliximab; Infliximab + Ustekinumab

Ustekinumab BIOLOGICAL

Ustekinumab: first dose i.v. at Week 0 (Patients with body weight ≤55 kg - 260 mg, patients with body weight \>55-≤85 kg 390 mg, patients with body weight \>85 kg - 520 mg) then 90 mg s.c. every 8/12 weeks for 52 weeks.

Infliximab + Ustekinumab; Ustekinumab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Obtaining informed, written consent for the patient's participation in the in the study and for all planned procedures.
• Age ≥ 18 years and ≤65 at the time of screening.
• In the case of women of reproductive potential, agreement to not donate oocytes for the entire period of participation in the in the study and 6 months after receiving the last dose of the drug.
• For women of reproductive potential, agreement to use effective contraception (Table 4) during the entire period, during which the patient participates in the study and for a period counted from the last dose of 15 weeks if using UST (patients in arms B and C) or 6 months if using IFX (patients in arm A).
• Negative serum or urine pregnancy test in women of childbearing age.
• Diagnosis of UC a minimum of. 3 months prior to screening documented by:
• (a) medical source documentation of the patient with the result of an endoscopic examination that diagnosed features typical of UC.
• (b) a histopathological examination result consistent with UC. In the absence of a histopathological result, it is possible to take sections during the endoscopic examination for histopathological evaluation at the time of eligibility for the study with subsequent sending of the material to the local pathomorphology laboratory to confirm the diagnosis of UC before randomization.
• UC with moderate or severe activity defined as a Mayo scale score (Appendix 2) of 7 to 12 including the following sub-item values (each sub-item 0-3 points depending on the severity of the lesions):
• \- Frequency of bowel movements
• Bowel bleeding
• Endoscopic image of the colonic mucosa
• General medical evaluation and:
• with inadequate response to standard treatment, including corticosteroids and 6-mercaptopurine or azathioprine, or.
• intolerant of treatment with corticosteroids and 6-mercaptopurine or azathioprine, or

You may not qualify if:

• Previous use of the study drug IFX or UST.
• Hypersensitivity to the active substance or excipients.
• Moderate or severe myocardial insufficiency (NYHA III or IV).
• Unstable coronary artery disease.
• History of serious cerebrovascular disease (stroke, intracranial hemorrhage, transient cerebral ischemia) within the last 24 weeks prior to screening.
• Chronic respiratory failure.
• Severe chronic renal failure.
• Severe chronic liver failure.
• Demyelinating syndrome or symptoms resembling the syndrome.
• Alcoholic disease, post-alcoholic liver damage.
• Diagnosis of malignant neoplasms, including within 5 years preceding the time of eligibility for the program (except for carcinoma in situ of the cervix, and non-melanoma skin cancers).
• Complications requiring other management (e.g., surgery). 13. Current or recent (defined as an incident within 12 weeks prior to randomization) documented episode of fulminant colitis, or intra-abdominal abscess, or acute colonic distension, or bowel perforation.
• \. Status after extensive colorectal resection, subtotal or total colectomy with or without colostomy, or J-pouch reservoir.
• \. Indication of surgical intervention due to underlying disease or when there is a suspicion of need for such intervention during the course of the study.
• \. History of current or previously documented unclassified colitis or ischemic colitis.

Sponsors & Collaborators

• Medical University of Lodz: lead
• Poznan University of Medical Sciences: collaborator
• Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań: collaborator
• Norbert Barlicki Memorial Teaching Hospital No. 1 of the Medical University of Lodz: collaborator
• Medical Research Agency, Poland: collaborator

Study Sites (1)

Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej USK nr 1 im. N. Barlickiego w Łodzi

Lodz, 90-153, Poland

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Infliximab; Ustekinumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Study Officials

• Renata Talar-Wojnarowska, Prof.

  Medical University of Lodz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Renata Talar-Wojnarowska, Prof.

CONTACT

+48426776664; renata.talar-wojnarowska@umed.lodz.pl

Adam Fabisiak, PhD, MD

CONTACT

+48500316396; adam.fabisiak@umed.lodz.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the comparative nature of the study, aiming to compare the effectiveness of dual biological therapy with biologic drugs administered solely, we have not implemented treatment blinding. However, a blinded central endoscopy reader was included. Each endoscopy procedure will be recorded using an external device and sent to the central reader who will be blinded to the patient's treatment arm. It is important to note that the final decision regarding the endoscopic disease activity will remain with the endoscopist performing the procedure.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: June 11, 2024
• Study Start: February 17, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 15, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)