Ulcerative ColitisPhase 3NCT00537316

Efficacy & Safety of Infliximab Monotherapy Vs Combination Therapy Vs AZA Monotherapy in Ulcerative Colitis (Part 1) Maintenance Vs Intermittent Therapy for Maintaining Remission (Part 2)(Study P04807)

A Phase 3 study testing Infliximab (IFX) and Azathioprine (AZA) in people with Ulcerative Colitis, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Part 1 of this study is a 3-arm, randomized, active-controlled, parallel-group, multicenter, double-blind, double-dummy, 16-week study to compare the efficacy and safety of infliximab (IFX), as monotherapy or in combination with azathioprine (AZA) versus AZA monotherapy in adults with moderate to severe active… Read more about this study

Who is it for?: Ages 21 years and older
Conditions the study is for: Ulcerative Colitis
What is being tested?: Infliximab (IFX) and Azathioprine (AZA)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 242 participants
Where: No sites listed yet
Study dates: Jul 2007to Feb 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

must be >=21 years of age at the time of informed consent, of either sex, and of any race;
must have endoscopic evidence of UC, as determined by sigmoidoscopy, within 14 days prior to Baseline;
must have a total Mayo score of 6 to 12 points at Baseline;
must have responded inadequately to corticosteroid treatment (ie, the last or current UC flare did not respond adequately to a standard course of corticosteroids) with or without 5 aminosalicylic acid (5-ASA);
must be off corticosteroids or on a stable dose of corticosteroid for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroid at Baseline must not exceed the equivalent of 30 mg of prednisone;
must be naïve to infliximab and other tumor necrosis factor-alpha (TNF-α) antagonists;

Show all 21Show fewer

must be either naïve to AZA/6-MP or have not received AZA/6-MP for at least 3 months before enrollment in the study;
considered eligible according to the following tuberculosis (TB) screening criteria:
have no history of latent or active TB prior to Screening;
have no signs or symptoms suggestive of active TB upon medical history and/or physical examination;
have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of IFX;
within 1 month prior to the first administration of infliximab, either have negative tuberculin skin test OR have a newly identified positive tuberculin test during Screening in which active TB has been ruled out, and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of IFX.
must have a chest X-ray (posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old active TB;
have had UC for more than 10 years should have had a full colonoscopy within 2 years prior to Screening for the surveillance of dysplasia;
screening and Baseline clinical laboratory tests (complete blood count [CBC] and blood chemistries) must be within predetermined parameters
had been on antibiotics for the treatment of UC (eg, ciprofloxacin and metronidazole) must have been discontinued from them at least 3 weeks prior to Screening;
must be free of any clinically significant condition or situation, other than UC that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study;
willing and able to adhere to the study visit schedule and other protocol requirements;
capable of providing written informed consent, which must be obtained prior to conducting any protocol-specified procedures;
women of child-bearing potential and all men must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study;
female participants of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin) at Screening and a negative urine pregnancy test at Baseline.

Who cannot join

have severe extensive colitis as evidenced by:
investigator judgment that the participant is likely to require colectomy within 12 weeks of Baseline
OR
at least 4 of these symptoms at Screening or Baseline visits, as follows:
diarrhea with >=6 bowel movements/day with macroscopic blood in stool;
focal severe or rebound abdominal tenderness;

Show all 37Show fewer

persistent fever (>=37.5 degrees C) for at least 3 days prior to baseline;
tachycardia (>100 beats/minute);
hemoglobin <8.5 g/dL (5.3 mM/L).
require, or are required within the 2 months prior to baseline, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage or other conditions possibly confounding the evaluation of disease activity;
have severe, fixed symptomatic stenosis of the large or small intestine;
have current evidence of colonic obstruction or history within the 6 months prior to baseline, confirmed with objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy);
have a history of colonic mucosal dysplasia;
presence on screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed;
have the presence of a stoma;
have a history of extensive colonic resection that would prevent adequate evaluation of clinical disease activity (eg, less than 30 cm of colon remaining);
have had a positive stool culture for enteric pathogens, pathogenic ova or parasites within 4 months prior to Baseline unless participant has received treatment and had a negative stool examination 1 week or longer after the end of treatment;
have a concomitant diagnosis of congestive heart failure (CHF), including medically controlled asymptomatic subjects;
have had serious infections (eg, active hepatitis, pneumonia, or pyelonephritis) within 2 months of Screening. Less serious infections (such as acute upper respiratory tract infection [colds] or a simple urinary tract infection) need not be considered as an exclusion at the discretion of the investigator;
have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to Screening;
have a known infection with human immunodeficiency virus (HIV) and/or hepatitis B or hepatitis C;
have a history of a known allergy to murine proteins or allergy/sensitivity to study drug or its excipients;
have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases;
have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis;
presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to Screening);
have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly;
have any current known malignancy or malignancy within 5 years prior to Screening (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
have poor tolerability of venipuncture or lack of adequate venous access for required blood sampling and infusion of study drug during the study period;
have had a known substance abuse or dependency (drug or alcohol) within 3 years of Screening;
require chronic (>=1 month) and frequent use (>=3 days per week)of nonsteroidal anti-inflammatory drugs (NSAIDs) except low-dose aspirin for prevention of heart attacks, unstable angina, or transient ischemic attacks;
have other inflammatory diseases that might interfere with the evaluation of the ulcerative colitis;
have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to Screening.
have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of Screening.
have had a chest X-ray within the 3 months prior to the first administration of study agent that shows an abnormality suggestive of malignancy or current active infection, including TB.
have received any specified prohibited treatment more recently than the indicated washout period prior to Screening;
who are participating in any other clinical study or who have received treatment with any investigational drug or device within 3 months prior Screening;
who is part of the staff or a family member of the staff personnel directly involved with this study.

About this study

Official title: Comparison of the Efficacy and Safety of Infliximab, as Monotherapy or in Combination With Azathioprine, Versus Azathioprine Monotherapy in Moderate to Severe Active Ulcerative Colitis (Part 1) Comparison of Maintenance Versus Intermittent Infliximab Treatment in Maintaining Remission: A Follow-Up of Efficacy and Safety (Part 2)

Participants in the IFX/AZA combination therapy and IFX monotherapy cohorts will receive IFX infusions at Weeks 0, 2, and 6 and daily oral AZA/placebo, respectively; participants in the AZA cohort will receive daily oral AZA and placebo infusions at Weeks 0, 2, and 6. At Week 8, all participants will be evaluated for response.

Participants responding to IFX treatment at Week 8, either as monotherapy or in combination with AZA, will receive one more IFX infusion at Week 14; non-responders to IFX therapy will receive placebo infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14.

Participants responding to AZA monotherapy at Week 8 will continue on AZA therapy and receive one placebo infusion at Week 14; nonresponders to AZA will be eligible to receive IFX at Weeks 8, 10, and 14.

Part 2: Participants in remission on IFX monotherapy or IFX/AZA treatment at Week 16 will be randomized to either maintenance or intermittent open-label IFX treatment; randomization will be stratified based on oral AZA/placebo treatment in Part 1. Oral AZA/placebo treatment will continue to be double-blinded. All participants will continue to receive oral AZA/ placebo for the duration of the study.

Participants randomized to maintenance IFX treatment will receive scheduled IFX infusions every 8 weeks beginning at Week 22 (Week 6 for direct entry). If participants lose response, or if treatment has to be discontinued because of an adverse event, these participants are considered treatment failures, and should be followed up for safety at the scheduled 6-month visits (Weeks 38, 62, and 94 [Weeks 22, 46, and 78 for direct entry]). These participants will receive standard of care per their personal physician.

Participants randomized to intermittent IFX treatment will be evaluated every 8 weeks. Participants will receive IFX only upon relapse of disease. Treatment with IFX will be initiated at Weeks 0, 2, and 6 of the individual treatment cycle and will continue every 8 weeks until remission is regained. Throughout the study, individual treatment cycles will be repeated whenever a subject relapses.

In addition, to facilitate enrollment into Part 2, participants who received treatment outside of Part 1 and who are in remission on IFX with or without AZA/6-mercaptopurine (6-MP) will be allowed to enter directly into Part 2. In the Czech Republic, direct entry into Part 2 of the study is not allowed.

A higher than expected incidence of serious infusion reactions observed in the intermittent treatment arm of another study (Protocol P04563, NCT0358670) conducted in participants with moderate to severe psoriasis resulted in the termination of that study. Based on the similarities in study design between the intermittent treatment arm of P04563 and the intermittent treatment arm of Part 2 of this study, enrollment to Part 2 of this study was put on hold, for precautionary reasons. At the same time, all participants already enrolled in the intermittent treatment arm of Part 2 were asked to discontinue from the trial. In October 2009, a decision was made by the sponsor to terminate the whole study (Part 1 and 2). At that time, participants enrolled in Part 1 of the study were allowed to complete their treatment up to Week 16.

Conditions: Ulcerative Colitis
Being tested: Infliximab (IFX), Azathioprine (AZA), Placebo to Azathioprine, Placebo infusion
Medical subject headings: Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Infliximab (IFX)Biological
Also called Remicade
IFX intravenous (IV) infusion dosed at 5mg/kg of body weight
Azathioprine (AZA)Drug
Also called Imuran
AZA 50 mg tablet dosed at 2.5 mg/kg of body weight orally every day
Placebo to AzathioprineDrug
Placebo to AZA tablet orally every day
Placebo infusionDrug
Placebo to IFX intravenous (IV) infusion

Study groups in NCT00537316
Study group	Role	What they receive
Infliximab (IFX)	Experimental	Part 1: IFX 5 mg/kg of body weight intravenous (IV) infusions was to be administered at Weeks 0, 2, and 6 and placebo to AZA was to be taken orally every day for 16 weeks. Responders to IFX at Week 8, were to receive one more IFX infusion at Week 14; non-responders to IFX were to receive placebo IFX infusions at Weeks 8 and 10 and an additional IFX infusion at Week 14. Part 2: Participants in steroid-free remission at Week 16 of Part 1 were to be randomized to either maintenance (every 8 weeks [q8w]) or intermittent (upon relapse) open-label IFX (last IFX infusion administered at Week 86) plus double-blind oral AZA/placebo treatment as allocated in Part 1 (last dose at the final visit, Week 94). Responders at Week 16 who had not achieved steroid-free remission were to continue to receive IFX infusions every 8 weeks. Receives: Biological: Infliximab (IFX); Drug: Placebo to Azathioprine; Drug: Placebo infusion
Azathioprine (AZA)	Active comparator	AZA 2.5 mg/kg of body weight orally every day for 16 weeks. Responders to AZA monotherapy at Week 8 were to continue on AZA therapy and receive one placebo infusion at Week 14; non-responders to AZA at Week 8 would be eligible to receive an IFX infusion at Weeks 8, 10, and 14. Participants in steroid-free remission at Week 16 were to continue on AZA monotherapy and were to be followed up for safety in Part 2. Participants who experienced a relapse of disease after Week 16 were to continue daily AZA monotherapy and receive 3 infusions of IFX (induction therapy at Weeks 0, 2, and 6) followed by infusions every 8 weeks (maintenance therapy). Receives: Drug: Azathioprine (AZA); Drug: Placebo infusion
IFX/AZA	Experimental	IFX 5 mg/kg of body weight IV infusions at Weeks 0, 2, and 6 plus AZA 2.5 mg/kg orally every day for 16 weeks. Responders to IFX/AZA at Week 8 were to receive one more IFX infusion at Week 14; non-responders to IFX/AZA were to receive placebo infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14. Part 2: Participants in steroid-free remission at Week 16 of Part 1 were to be randomized to either maintenance (every 8 weeks [q8w]) or intermittent (upon relapse) open-label IFX (last IFX infusion administered at Week 86) plus double-blind oral AZA/placebo treatment as allocated in Part 1 (last dose at the final visit, Week 94). Responders at Week 16 who had not achieved steroid-free remission were to continue to receive IFX infusions every 8 weeks. Receives: Biological: Infliximab (IFX); Drug: Azathioprine (AZA); Drug: Placebo infusion
Maintenance IFX/AZA (during Part 2)	Experimental	Participants randomized to maintenance IFX/AZA in Part 2 of the study were to receive IFX 5 mg/kg of body weight IV infusions every 8 weeks (beginning at Week 22, Week 6 for direct entry) plus AZA 2.5 mg/kg of body weight daily. Four participants were from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study. Receives: Biological: Infliximab (IFX); Drug: Azathioprine (AZA)
Maintenance IFX (during Part 2)	Experimental	Participants randomized to maintenance IFX were to receive IFX 5 mg/kg of body weight IV infusions every 8 weeks (beginning at Week 22, Week 6 for direct entry) in Part 2 of the study. Placebo to AZA therapy was to continue as allocated in Part 1 of the study. All participants were from Part 1 of the study. Receives: Biological: Infliximab (IFX)
Intermittent IFX/AZA (during Part 2)	Experimental	Participants randomized to intermittent IFX/AZA were to receive IFX 5 mg/kg of body weight IV infusions only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study. Three participants were from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study. Receives: Biological: Infliximab (IFX); Drug: Azathioprine (AZA)
Intermittent IFX (during Part 2)	Experimental	Participants randomized to intermittent IFX were to receive IFX 5 mg/kg of body weight IV infusions only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained). Placebo to AZA therapy was to continue as allocated in Part 1 of the study. One participant was from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study. Receives: Biological: Infliximab (IFX)

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of Participants in Steroid-free Remission at Week 16
Steroid-free remission is defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point, without the use of corticosteroids. The total Mayo score consists of the following 4 sub-scores: stool frequency, rectal bleeding, findings of endoscopy (sigmoidoscopy), and physician's global assessment.
Measured: 16 weeks
Average Remission Rate During Part 2 of the Study
Due to the early termination of this study, evaluations of efficacy were not conducted for Part 2 of the study (Week 38 through Week 94 [Week 22 through Week 78 for direct entry]).
Measured: up to Week 94 (Week 78 for direct entry)

Secondary outcomes (4)

Proportion of Participants in Response at Weeks 8 and 16
Response at Week 8 is defined as a decrease in the partial Mayo score of ≥1 point. Response at Week 16 is defined as a decrease in total Mayo score of ≥3 points and at least 30% lower than baseline Mayo score. The partial Mayo score consists of the following 3 sub-scores: stool frequency, rectal bleeding, and physician's global assessment. The total Mayo score consists of the following 4 sub-scores: stool frequency, rectal bleeding, findings of endoscopy (sigmoidoscopy), and physician's global assessment.
Measured: Weeks 8 and 16
Proportion of Participants With Mucosal Healing at Week 16
Mucosal healing was defined as a Mayo endoscopy score of 0 or 1.
Measured: 16 weeks
Proportion of Participants Who Are in Steroid-free Remission During Part 2 of the Study
Due to the early termination of this study, evaluations of efficacy were not conducted for Part 2 of the study.
Measured: Weeks 38, 62 & 94 (Weeks 22, 46 and 78 for direct entry)
Proportion of Participants With Mucosal Healing During Part 2 of the Study
Due to the early termination of this study, evaluations of efficacy were not conducted for Part 2 of the study
Measured: Weeks 38, 62 and 94 (Weeks 22, 46 and 78 for direct entry)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Feb 2010

First posted1 Oct 2007 (estimated)
Study startJul 2007
Primary completionFeb 2010
Study completionFeb 2010

Why it stopped: Infusion reactions during re-induction cycles after a period of no treatment in another study \[P04563, NCT0358670\]

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 242 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00537316
Sponsor's protocol ID: P04807
Status last verified: Mar 2017
First submitted: 28 Sep 2007
Last updated: 12 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Panaccione R, Ghosh S, Middleton S, Marquez JR, Scott BB, Flint L, van Hoogstraten HJ, Chen AC, Zheng H, Danese S, Rutgeerts P. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014 Feb;146(2):392-400.e3. doi: 10.1053/j.gastro.2013.10.052.
PubMed 24512909
Hasskamp J, Meinhardt C, Patton PH, Timmer A. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.
PubMed 40013523

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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IBD, Ulcerative Colitis
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Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease

All Ulcerative Colitis trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparison of the Efficacy and Safety of Infliximab, as Monotherapy or in Combination With Azathioprine, Versus Azathioprine Monotherapy in Moderate to Severe Active Ulcerative Colitis (Part 1) Comparison of Maintenance Versus Intermittent Infliximab Treatment in Maintaining Remission: A Follow-Up of Efficacy and Safety (Part 2)
ClinicalTrials.gov ID: NCT00537316
Acronym / sponsor ID: P04807
Conditions: Ulcerative Colitis
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Infusion reactions during re-induction cycles after a period of no treatment in another study \[P04563, NCT0358670\]
Enrolment: 242 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Jul 2007
Primary completion: Feb 2010 (actual)
Study completion: Feb 2010 (actual)
First posted: 1 Oct 2007 (estimated)
Results: Posted 16 Dec 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 7

Arm	Type	Receives
Infliximab (IFX)	Experimental	Biological: Infliximab (IFX), Drug: Placebo to Azathioprine, Drug: Placebo infusionPart 1: IFX 5 mg/kg of body weight intravenous (IV) infusions was to be administered at Weeks 0, 2, and 6 and placebo to AZA was to be taken orally every day for 16 weeks. Responders to IFX at Week 8, were to receive one more IFX infusion at Week 14; non-responders to IFX were to receive placebo IFX infusions at Weeks 8 and 10 and an additional IFX infusion at Week 14. Part 2: Participants in steroid-free remission at Week 16 of Part 1 were to be randomized to either maintenance (every 8 weeks [q8w]) or intermittent (upon relapse) open-label IFX (last IFX infusion administered at Week 86) plus double-blind oral AZA/placebo treatment as allocated in Part 1 (last dose at the final visit, Week 94). Responders at Week 16 who had not achieved steroid-free remission were to continue to receive IFX infusions every 8 weeks.
Azathioprine (AZA)	Active comparator	Drug: Azathioprine (AZA), Drug: Placebo infusionAZA 2.5 mg/kg of body weight orally every day for 16 weeks. Responders to AZA monotherapy at Week 8 were to continue on AZA therapy and receive one placebo infusion at Week 14; non-responders to AZA at Week 8 would be eligible to receive an IFX infusion at Weeks 8, 10, and 14. Participants in steroid-free remission at Week 16 were to continue on AZA monotherapy and were to be followed up for safety in Part 2. Participants who experienced a relapse of disease after Week 16 were to continue daily AZA monotherapy and receive 3 infusions of IFX (induction therapy at Weeks 0, 2, and 6) followed by infusions every 8 weeks (maintenance therapy).
IFX/AZA	Experimental	Biological: Infliximab (IFX), Drug: Azathioprine (AZA), Drug: Placebo infusionIFX 5 mg/kg of body weight IV infusions at Weeks 0, 2, and 6 plus AZA 2.5 mg/kg orally every day for 16 weeks. Responders to IFX/AZA at Week 8 were to receive one more IFX infusion at Week 14; non-responders to IFX/AZA were to receive placebo infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14. Part 2: Participants in steroid-free remission at Week 16 of Part 1 were to be randomized to either maintenance (every 8 weeks [q8w]) or intermittent (upon relapse) open-label IFX (last IFX infusion administered at Week 86) plus double-blind oral AZA/placebo treatment as allocated in Part 1 (last dose at the final visit, Week 94). Responders at Week 16 who had not achieved steroid-free remission were to continue to receive IFX infusions every 8 weeks.
Maintenance IFX/AZA (during Part 2)	Experimental	Biological: Infliximab (IFX), Drug: Azathioprine (AZA)Participants randomized to maintenance IFX/AZA in Part 2 of the study were to receive IFX 5 mg/kg of body weight IV infusions every 8 weeks (beginning at Week 22, Week 6 for direct entry) plus AZA 2.5 mg/kg of body weight daily. Four participants were from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study.
Maintenance IFX (during Part 2)	Experimental	Biological: Infliximab (IFX)Participants randomized to maintenance IFX were to receive IFX 5 mg/kg of body weight IV infusions every 8 weeks (beginning at Week 22, Week 6 for direct entry) in Part 2 of the study. Placebo to AZA therapy was to continue as allocated in Part 1 of the study. All participants were from Part 1 of the study.
Intermittent IFX/AZA (during Part 2)	Experimental	Biological: Infliximab (IFX), Drug: Azathioprine (AZA)Participants randomized to intermittent IFX/AZA were to receive IFX 5 mg/kg of body weight IV infusions only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study. Three participants were from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study.
Intermittent IFX (during Part 2)	Experimental	Biological: Infliximab (IFX)Participants randomized to intermittent IFX were to receive IFX 5 mg/kg of body weight IV infusions only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained). Placebo to AZA therapy was to continue as allocated in Part 1 of the study. One participant was from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study.

Who may qualify

Ages: 21 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

must be >=21 years of age at the time of informed consent, of either sex, and of any race;
must have endoscopic evidence of UC, as determined by sigmoidoscopy, within 14 days prior to Baseline;
must have a total Mayo score of 6 to 12 points at Baseline;
must have responded inadequately to corticosteroid treatment (ie, the last or current UC flare did not respond adequately to a standard course of corticosteroids) with or without 5 aminosalicylic acid (5-ASA);
must be off corticosteroids or on a stable dose of corticosteroid for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroid at Baseline must not exceed the equivalent of 30 mg of prednisone;

Key exclusion criteria (37 listed)

have severe extensive colitis as evidenced by:
OR
at least 4 of these symptoms at Screening or Baseline visits, as follows:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Infliximab (IFX)Also: RemicadeIFX intravenous (IV) infusion dosed at 5mg/kg of body weight	Biological	IFX/AZA, Infliximab (IFX), Intermittent IFX (during Part 2), Intermittent IFX/AZA (during Part 2), Maintenance IFX (during Part 2), Maintenance IFX/AZA (during Part 2)
Azathioprine (AZA)Also: ImuranAZA 50 mg tablet dosed at 2.5 mg/kg of body weight orally every day	Drug	Azathioprine (AZA), IFX/AZA, Intermittent IFX/AZA (during Part 2), Maintenance IFX/AZA (during Part 2)
Placebo to AzathioprinePlacebo to AZA tablet orally every day	Drug	Infliximab (IFX)
Placebo infusionPlacebo to IFX intravenous (IV) infusion	Drug	Azathioprine (AZA), IFX/AZA, Infliximab (IFX)

Primary outcome

Proportion of Participants in Steroid-free Remission at Week 16
Time frame: 16 weeks
Steroid-free remission is defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point, without the use of corticosteroids. The total Mayo score consists of the following 4 sub-scores: stool frequency, rectal bleeding, findings of endoscopy (sigmoidoscopy), and physician's global assessment.
Average Remission Rate During Part 2 of the Study
Time frame: up to Week 94 (Week 78 for direct entry)
Due to the early termination of this study, evaluations of efficacy were not conducted for Part 2 of the study (Week 38 through Week 94 [Week 22 through Week 78 for direct entry]).

4 secondary outcomes

Proportion of Participants in Response at Weeks 8 and 16
Time frame: Weeks 8 and 16
Proportion of Participants With Mucosal Healing at Week 16
Time frame: 16 weeks
Proportion of Participants Who Are in Steroid-free Remission During Part 2 of the Study
Time frame: Weeks 38, 62 & 94 (Weeks 22, 46 and 78 for direct entry)
Proportion of Participants With Mucosal Healing During Part 2 of the Study
Time frame: Weeks 38, 62 and 94 (Weeks 22, 46 and 78 for direct entry)

Results and safety

Results posted to the registry on 16 Dec 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Infliximab (IFX)	79	65
Azathioprine (AZA)	80	53
IFX/AZA	80	63
Maintenance IFX/AZA (During Part 2)	0	0
Maintenance IFX (During Part 2)	0	0
Intermittent IFX/AZA (During Part 2)	0	0
Intermittent IFX (During Part 2)	0	0

Primary outcome: Proportion of Participants in Steroid-free Remission at Week 16

Time frame: 16 weeks. Number. Unit: Proportion of participants

Measure	Infliximab (IFX) n = 77	Azathioprine (AZA) n = 76	IFX/AZA n = 78
Value	0.22	0.24	0.40

Azathioprine (AZA) vs IFX/AZA: p = 0.032, Chi-squared

Population analysed: Full Analysis Set (participants who were randomized, received at least one dose of study treatment, and had data available for baseline and at least one post baseline evaluation). Participants who dropped out prior to Week 16, had a missing Mayo score at Week 16, or were non-responders at Week 8 are considered failures (non-remission) at Week 16.

Primary outcome: Average Remission Rate During Part 2 of the Study

Time frame: up to Week 94 (Week 78 for direct entry)

The sponsor has not posted figures for this outcome.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were categorized by 3 separate timeframes: Through Week 8 (AEs reported through Week 8 of Part 1), After Week 8 (AEs reported after Week 8 through Week 16 of Part 1), and Part 2 (AEs reported during Part 2). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZA Through Week 8	5 of 79 (6.3%)	27 of 79 (34.2%)	Not reported
IFX/AZA Through Week 8	4 of 80 (5%)	17 of 80 (21.3%)	Not reported
IFX Through Week 8	3 of 78 (3.8%)	17 of 78 (21.8%)	Not reported
AZA After Week 8	0 of 42 (0%)	8 of 42 (19%)	Not reported
AZA to IFX/AZA After Week 8	1 of 20 (5%)	3 of 20 (15%)	Not reported
IFX/AZA After Week 8	0 of 72 (0%)	13 of 72 (18.1%)	Not reported
IFX After Week 8	5 of 74 (6.8%)	9 of 74 (12.2%)	Not reported
Maintenance IFX/AZA (Part 2)	0 of 5 (0%)	3 of 5 (60%)	Not reported
Maintenance IFX (Part 2)	0 of 2 (0%)	1 of 2 (50%)	Not reported
Intermittent IFX/AZA (Part 2)	0 of 4 (0%)	2 of 4 (50%)	Not reported
Intermittent IFX (Part 2)	0 of 2 (0%)	0 of 2 (0%)	Not reported
AZA (Part 2)	1 of 10 (10%)	2 of 10 (20%)	Not reported
IFX/AZA (Part 2)	0 of 48 (0%)	12 of 48 (25%)	Not reported
IFX (Part 2)	3 of 37 (8.1%)	6 of 37 (16.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24512909Panaccione R, Ghosh S, Middleton S, Marquez JR, Scott BB, Flint L, van Hoogstraten HJ, Chen AC, Zheng H, Danese S, Rutgeerts P. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014 Feb;146(2):392-400.e3. doi: 10.1053/j.gastro.2013.10.052.
Derived from this study: PubMed 40013523Hasskamp J, Meinhardt C, Patton PH, Timmer A. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Infliximab (IFX) and Azathioprine (AZA) in people with Ulcerative Colitis, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants in Steroid-free Remission at Week 16 (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00537316, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2017.