Trial Outcomes & Findings for Conventional Step-Up Versus Infliximab Monotherapy in Patients With Ulcerative Colitis (P05553) (NCT NCT00984568)
NCT ID: NCT00984568
Last Updated: 2017-04-13
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
28 participants
Primary outcome timeframe
Week 50
Results posted on
2017-04-13
Participant Flow
Participant milestones
| Measure |
Top-Hold
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.
|
Step-Up
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 Study
STARTED
|
15
|
13
|
|
Overall Study
COMPLETED
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
8
|
6
|
Reasons for withdrawal
| Measure |
Top-Hold
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.
|
Step-Up
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 Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Did Not Meet Randomization Criteria
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Opportunistic Infection
|
1
|
0
|
|
Overall Study
Unknown Reason
|
1
|
3
|
Baseline Characteristics
Conventional Step-Up Versus Infliximab Monotherapy in Patients With Ulcerative Colitis (P05553)
Baseline characteristics by cohort
| Measure |
Top-Hold
n=15 Participants
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.
|
Step-Up
n=13 Participants
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
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.9 years
STANDARD_DEVIATION 15.2 • n=5 Participants
|
41.6 years
STANDARD_DEVIATION 15.3 • n=7 Participants
|
40.7 years
STANDARD_DEVIATION 15.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 50Population: The FAS consisted of all randomized participants who received at least one dose of study treatment.
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).
Outcome measures
| Measure |
Top-Hold
n=15 Participants
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.
|
Step-Up
n=13 Participants
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.
|
|---|---|---|
|
Number of Participants With Response at Week 4 and Steroid-Free Remission at Week 50
|
5 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Up to Week 4Population: The full analysis set (FAS) consisted of all randomized participants who received at least one dose of study treatment.
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).
Outcome measures
| Measure |
Top-Hold
n=15 Participants
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.
|
Step-Up
n=13 Participants
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.
|
|---|---|---|
|
Number of Participants Achieving Treatment Response
|
10 Participants
|
10 Participants
|
Adverse Events
Top-Hold
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Step-Up
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Top-Hold
n=15 participants at risk
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.
|
Step-Up
n=13 participants at risk
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Vascular disorders
Embolism
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
General disorders
Pyrexia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
Other adverse events
| Measure |
Top-Hold
n=15 participants at risk
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.
|
Step-Up
n=13 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
26.7%
4/15 • Number of events 4 • Up to Week 50
|
46.2%
6/13 • Number of events 6 • Up to Week 50
|
|
Infections and infestations
Gastrointestinal Viral Infection
|
0.00%
0/15 • Up to Week 50
|
15.4%
2/13 • Number of events 2 • Up to Week 50
|
|
Infections and infestations
Borrelia Infection
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Infections and infestations
Candidiasis
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Infections and infestations
Clostridial Infection
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Infections and infestations
Gastroenteritis Astroviral
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Infections and infestations
Gastroenteritis Norovirus
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Infections and infestations
Giardiasis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Infections and infestations
Helicobacter Gastritis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Infections and infestations
Herpes Simplex
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Infections and infestations
Herpes Zoster
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Infections and infestations
Hordeolum
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 2 • Up to Week 50
|
|
Infections and infestations
Scarlet Fever
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Gastrointestinal disorders
Gastritis
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/15 • Up to Week 50
|
23.1%
3/13 • Number of events 4 • Up to Week 50
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15 • Number of events 2 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Colitis Ulcerative
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Gastrointestinal disorders
Gastritis Erosive
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Reflux Oesophagitis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
6.7%
1/15 • Number of events 2 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
15.4%
2/13 • Number of events 3 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/15 • Up to Week 50
|
15.4%
2/13 • Number of events 2 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Muskuloskeletal Discomfort
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
General disorders
Pyrexia
|
13.3%
2/15 • Number of events 3 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
General disorders
Infusion Related Reaction
|
6.7%
1/15 • Number of events 9 • Up to Week 50
|
7.7%
1/13 • Number of events 2 • Up to Week 50
|
|
General disorders
Oedema Peripheral
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
General disorders
Asthenia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Nervous system disorders
Headache
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
15.4%
2/13 • Number of events 3 • Up to Week 50
|
|
Nervous system disorders
Intercostal Neuralgia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Nervous system disorders
Neuralgia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Nervous system disorders
Sensory Loss
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Blood and lymphatic system disorders
Iron Deficiency Anaemia
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
15.4%
2/13 • Number of events 2 • Up to Week 50
|
|
Blood and lymphatic system disorders
Anaemia
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Cardiac disorders
Atrial Fibrillation
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Cardiac disorders
Cardiac Failure
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Cardiac disorders
Palpitations
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Immune system disorders
Hypersensitivity
|
13.3%
2/15 • Number of events 2 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Respiratory, thoracic and mediastinal disorders
Alveolitis
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Endocrine disorders
Cushing's Syndrome
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
|
Investigations
Coombs Test Positive
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.7%
1/15 • Number of events 1 • Up to Week 50
|
0.00%
0/13 • Up to Week 50
|
|
Vascular disorders
Aortic Arteriosclerosis
|
0.00%
0/15 • Up to Week 50
|
7.7%
1/13 • Number of events 1 • Up to Week 50
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER