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Conventional Step-Up Versus Infliximab Monotherapy in Patients With Ulcerative Colitis (P05553) (MUNIX)

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ClinicalTrials.gov Identifier: NCT00984568
Recruitment Status : Terminated (Due to slow recruitment the study was stopped prematurely.)
First Posted : September 25, 2009
Results First Posted : April 2, 2013
Last Update Posted : April 13, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colitis, Ulcerative
Interventions Biological: Infliximab
Drug: Prednisolone
Drug: 5-aminosalicylic acid
Drug: Azathioprine
Enrollment 28
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Top-Hold Step-Up
Hide Arm/Group Description Level 1: Infliximab IV 5 mg/kg at Weeks 0, 2, and 6, and every 8 weeks thereafter. Level 2: Infliximab IV 5 mg/kg every 4 weeks. Level 3: Prednisolone induction + AZA 2.0-2.5 mg/kg/day. Level 1: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral 5-aminosalicylic acid (5-ASA) 2 g/day. Level 2: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day. Level 3: Infliximab 5 mg/kg at Weeks 0, 2, and 6 and every 8 weeks thereafter.
Period Title: Overall Study
Started 15 13
Completed 7 7
Not Completed 8 6
Reason Not Completed
Withdrawal by Subject             1             2
Lack of Efficacy             2             0
Adverse Event             2             0
Did Not Meet Randomization Criteria             1             0
Lost to Follow-up             0             1
Opportunistic Infection             1             0
Unknown Reason             1             3
Arm/Group Title Top-Hold Step-Up Total
Hide Arm/Group Description Level 1: Infliximab IV 5 mg/kg at Weeks 0, 2, and 6, and every 8 weeks thereafter. Level 2: Infliximab IV 5 mg/kg every 4 weeks. Level 3: Prednisolone induction + AZA 2.0-2.5 mg/kg/day. Level 1: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral 5-aminosalicylic acid (5-ASA) 2 g/day. Level 2: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day. Level 3: Infliximab 5 mg/kg at Weeks 0, 2, and 6 and every 8 weeks thereafter. Total of all reporting groups
Overall Number of Baseline Participants 15 13 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 13 participants 28 participants
39.9  (15.2) 41.6  (15.3) 40.7  (15.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 13 participants 28 participants
Female
10
  66.7%
7
  53.8%
17
  60.7%
Male
5
  33.3%
6
  46.2%
11
  39.3%
1.Primary Outcome
Title Number of Participants With Response at Week 4 and Steroid-Free Remission at Week 50
Hide Description Response at Week 4 was defined as a minimum decrease from baseline in Mayo score of 3 points and 30%. Steroid-free remission at Week 50 was defined as a total Mayo score (including endoscopic assessment) of 2 points or lower and no individual subscore exceeding 1. The Mayo score consists of the following 4 subscores: stool frequency; rectal bleeding; endoscopy results; physician’s global assessment. Each subscore is rated on a scale from 0 (best) to 3 (worst). The total Mayo score is calculated as the sum of the 4 subscores and ranges from 0 (best) to 12 (worst).
Time Frame Week 50
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Top-Hold Step-Up
Hide Arm/Group Description:
Level 1: Infliximab IV 5 mg/kg at Weeks 0, 2, and 6, and every 8 weeks thereafter. Level 2: Infliximab IV 5 mg/kg every 4 weeks. Level 3: Prednisolone induction + AZA 2.0-2.5 mg/kg/day.
Level 1: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral 5-aminosalicylic acid (5-ASA) 2 g/day. Level 2: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day. Level 3: Infliximab 5 mg/kg at Weeks 0, 2, and 6 and every 8 weeks thereafter.
Overall Number of Participants Analyzed 15 13
Measure Type: Number
Unit of Measure: Participants
5 5
2.Secondary Outcome
Title Number of Participants Achieving Treatment Response
Hide Description

Response was defined as a minimum decrease from baseline in total Mayo score of 3 points and 30% up to and including 4 weeks after the start of treatment. The Mayo score consists of the following 4 subscores: stool frequency; rectal bleeding; endoscopy results; physician’s global assessment. Each subscore

is rated on a scale from 0 (best) to 3 (worst). The total Mayo score is calculated as the sum of the 4 subscores and ranges from 0 (best) to 12 (worst).

Time Frame Up to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Top-Hold Step-Up
Hide Arm/Group Description:
Level 1: Infliximab IV 5 mg/kg at Weeks 0, 2, and 6, and every 8 weeks thereafter. Level 2: Infliximab IV 5 mg/kg every 4 weeks. Level 3: Prednisolone induction + AZA 2.0-2.5 mg/kg/day.
Level 1: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral 5-aminosalicylic acid (5-ASA) 2 g/day. Level 2: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day. Level 3: Infliximab 5 mg/kg at Weeks 0, 2, and 6 and every 8 weeks thereafter.
Overall Number of Participants Analyzed 15 13
Measure Type: Number
Unit of Measure: Participants
10 10
Time Frame Up to Week 50
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Top-Hold Step-Up
Hide Arm/Group Description Level 1: Infliximab IV 5 mg/kg at Weeks 0, 2, and 6, and every 8 weeks thereafter. Level 2: Infliximab IV 5 mg/kg every 4 weeks. Level 3: Prednisolone induction + AZA 2.0-2.5 mg/kg/day.

Level 1: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral 5-aminosalicylic acid (5-ASA) 2

g/day. Level 2: Oral prednisolone (40 mg/day or 1 mg/kg/day in the case of non-response) + oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day. Level 3: Infliximab 5 mg/kg at Weeks 0, 2, and 6 and every 8 weeks thereafter.

All-Cause Mortality
Top-Hold Step-Up
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Top-Hold Step-Up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/15 (13.33%)      1/13 (7.69%)    
General disorders     
Pyrexia  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Emphysema  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Vascular disorders     
Embolism  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Top-Hold Step-Up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/15 (93.33%)      11/13 (84.62%)    
Blood and lymphatic system disorders     
Iron Deficiency Anaemia  1  2/15 (13.33%)  2 2/13 (15.38%)  2
Anaemia  1  2/15 (13.33%)  2 0/13 (0.00%)  0
Cardiac disorders     
Atrial Fibrillation  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Cardiac Failure  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Palpitations  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Endocrine disorders     
Cushing's Syndrome  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Eye disorders     
Conjunctivitis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Gastrointestinal disorders     
Gastritis  1  2/15 (13.33%)  2 1/13 (7.69%)  1
Nausea  1  0/15 (0.00%)  0 3/13 (23.08%)  4
Constipation  1  1/15 (6.67%)  1 1/13 (7.69%)  1
Abdominal Discomfort  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Abdominal Pain  1  1/15 (6.67%)  2 0/13 (0.00%)  0
Abdominal Pain Upper  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Colitis Ulcerative  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Diarrhoea  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Dyspepsia  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Flatulence  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Gastritis Erosive  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Haemorrhoids  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Periodontitis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Reflux Oesophagitis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Stomatitis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Toothache  1  0/15 (0.00%)  0 1/13 (7.69%)  1
General disorders     
Pyrexia  1  2/15 (13.33%)  3 1/13 (7.69%)  1
Infusion Related Reaction  1  1/15 (6.67%)  9 1/13 (7.69%)  2
Oedema Peripheral  1  1/15 (6.67%)  1 1/13 (7.69%)  1
Asthenia  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  2/15 (13.33%)  2 0/13 (0.00%)  0
Infections and infestations     
Nasopharyngitis  1  4/15 (26.67%)  4 6/13 (46.15%)  6
Gastrointestinal Viral Infection  1  0/15 (0.00%)  0 2/13 (15.38%)  2
Borrelia Infection  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Candidiasis  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Clostridial Infection  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Gastroenteritis Astroviral  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Gastroenteritis Norovirus  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Giardiasis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Helicobacter Gastritis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Herpes Simplex  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Herpes Zoster  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Hordeolum  1  0/15 (0.00%)  0 1/13 (7.69%)  2
Scarlet Fever  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Investigations     
Coombs Test Positive  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Metabolism and nutrition disorders     
Hypocalcaemia  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/15 (6.67%)  1 2/13 (15.38%)  3
Back Pain  1  0/15 (0.00%)  0 2/13 (15.38%)  2
Joint Swelling  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Muscular Weakness  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Muskuloskeletal Discomfort  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Pain in Extremity  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Nervous system disorders     
Headache  1  2/15 (13.33%)  2 2/13 (15.38%)  3
Intercostal Neuralgia  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Neuralgia  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Sensory Loss  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Alveolitis  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Cough  1  1/15 (6.67%)  1 0/13 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  2/15 (13.33%)  2 1/13 (7.69%)  1
Alopecia  1  2/15 (13.33%)  2 0/13 (0.00%)  0
Eczema  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Pruritus  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Erythema  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Psoriasis  1  1/15 (6.67%)  2 0/13 (0.00%)  0
Urticaria  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Vascular disorders     
Aortic Arteriosclerosis  1  0/15 (0.00%)  0 1/13 (7.69%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Due to slow recruitment the study was stopped prematurely; participants on study at that time continued to receive treatment per protocol.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator agrees to provide the sponsor 45 days prior to publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor has the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis with respect to: proprietary information, accuracy, and fair balance.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00984568     History of Changes
Other Study ID Numbers: P05553
2009-010065-23 ( EudraCT Number )
First Submitted: September 24, 2009
First Posted: September 25, 2009
Results First Submitted: February 19, 2013
Results First Posted: April 2, 2013
Last Update Posted: April 13, 2017