Trial Outcomes & Findings for Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis (NCT NCT01393405)
NCT ID: NCT01393405
Last Updated: 2018-04-17
Results Overview
Relapse-free survival: Total week 48 Mayo score not exceeding 2 points, with all individual subscores not exceeding 1 point and relapse free survival defined by a numerical stable Mayo score throughout 32 weeks of maintenance therapy without increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) compared to the partial Mayo score of the individual patient at randomization at week 16 and no steroid use or other immunosuppressive medication throughout the 32 week maintenance period.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
179 participants
Primary outcome timeframe
48 weeks
Results posted on
2018-04-17
Participant Flow
256 patients were assessed for eligibility between February 2012 and May 2016 at 37 sites across the US. 76 met exclusion criteria and one patient withdrew consent during screening.
Participant milestones
| Measure |
Induction Period (Week 1-16)
Steroid taper for 12 weeks and 25 mg MTX sq once weekly + 1 mg folic acid daily
|
Methotrexate Maintenance (Week 17-48)
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|---|
|
Induction Period (week1-16)
STARTED
|
179
|
0
|
0
|
|
Induction Period (week1-16)
COMPLETED
|
84
|
0
|
0
|
|
Induction Period (week1-16)
NOT COMPLETED
|
95
|
0
|
0
|
|
Maintenance Period Week
STARTED
|
0
|
44
|
40
|
|
Maintenance Period Week
COMPLETED
|
0
|
15
|
16
|
|
Maintenance Period Week
NOT COMPLETED
|
0
|
29
|
24
|
Reasons for withdrawal
| Measure |
Induction Period (Week 1-16)
Steroid taper for 12 weeks and 25 mg MTX sq once weekly + 1 mg folic acid daily
|
Methotrexate Maintenance (Week 17-48)
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|---|
|
Induction Period (week1-16)
Lack of Efficacy
|
70
|
0
|
0
|
|
Induction Period (week1-16)
Adverse Event
|
16
|
0
|
0
|
|
Induction Period (week1-16)
Withdrawal by Subject
|
9
|
0
|
0
|
|
Maintenance Period Week
Lack of Efficacy
|
0
|
22
|
22
|
|
Maintenance Period Week
Adverse Event
|
0
|
5
|
2
|
|
Maintenance Period Week
Withdrawal by Subject
|
0
|
1
|
0
|
|
Maintenance Period Week
Lost to Follow-up
|
0
|
1
|
0
|
Baseline Characteristics
Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis
Baseline characteristics by cohort
| Measure |
Induction Period (Week 1-16)
n=179 Participants
Steroid taper for 12 weeks and 25 mg MTX sq once weekly + 1 mg folic acid daily
|
|---|---|
|
Age, Continuous
|
42 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
69 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
110 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
169 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
155 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
179 Participants
n=5 Participants
|
|
Calprotectin week 0 (Induction period) or week 16 (Maintenance period)
|
612 mg/kg
STANDARD_DEVIATION 524 • n=5 Participants
|
|
Site of disease
Left colon
|
86 Participants
n=5 Participants
|
|
Site of disease
Pancolitis
|
93 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 weeksRelapse-free survival: Total week 48 Mayo score not exceeding 2 points, with all individual subscores not exceeding 1 point and relapse free survival defined by a numerical stable Mayo score throughout 32 weeks of maintenance therapy without increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) compared to the partial Mayo score of the individual patient at randomization at week 16 and no steroid use or other immunosuppressive medication throughout the 32 week maintenance period.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=44 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=40 Participants
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Relapse Free Survival Week 17-48
|
12 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 48 weeksMucosal healing is defined as an absolute Mayo subscore for endoscopy of 0 or 1
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=44 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=40 Participants
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Mucosal Healing at Week 48.
|
12 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 48 weeksRelapse of disease in the Maintenance period as defined as an increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) with an absolute clinical Mayo score ≥ 4 or need for retreatment with steroids.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=44 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=40 Participants
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Relapse of Disease Between Week 17-48
|
29 Participants
|
25 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 16 weeksPopulation: 134 /179 (75%) patients had a calprotectin value ≥ 250 mcg/g stool at screening.
Steroid free clinical remission as defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point or steroid free clinical response defined as a reduction from baseline in the clinical Mayo score of ≥ 2 points and at least 25%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0-1 point and a clinical Mayo score ≤5 and stool calprotectin levels \<250 mcg/g stool at week 16 of the induction period in the subgroup of patients with calprotectin \>250mcg/g stool at screening.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=134 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Calprotectin Levels <250 mcg/g Stool in Patients in Response or in Remission at Week 16 With Calprotectin Levels ≥ 250 mcg/g Stool at Screening
|
56 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 48 weeksPopulation: 33/44 patient in the Methotrexate Maintenance group and 32/40 patients in the Placebo Maintenance group met the criteria of calprotectin ≥ 250 mcg/g stool at screening
Steroid free clinical remission as defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point or steroid free clinical response defined as a reduction from baseline in the clinical Mayo score of ≥ 2 points and at least 25%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0-1 point and a clinical Mayo score ≤5 and stool calprotectin levels \<250 mcg/g stool at week 32 of the maintenance period in the subgroup of patients with calprotectin ≥ 250mcg/g stool at screening.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=33 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=32 Participants
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Calprotectin Levels <250 mcg/g Stool in Patients in Response or in Remission at Week 48 With Calprotectin Levels > 250 mcg/g Stool at Screening
|
10 Participants
|
8 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 16 weeksPopulation: 134 /179 (75%) patients had a calprotectin value ≥ 250 mcg/g stool at screening.
Steroid free clinical remission as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point and stool calprotectin levels of ≤ 50mcg at week 16 of the induction period in the subgroup of patients with calprotectin ≥ 250mcg/g stool at screening.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=134 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Calprotectin Levels < 50 mcg/g Stool in Patients in Remission at Week 16 With Calprotectin Levels ≥ 250 mcg/g Stool at Screening
|
10 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 48 weeksPopulation: 33/44 patient in the Methotrexate Maintenance group and 32/40 patients in the Placebo Maintenance group met the criteria of calprotectin ≥ 250 mcg/g stool at screening
Steroid free clinical remission as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point and stool calprotectin levels of ≤ 50mcg at week 48 of the induction period in the subgroup of patients with calprotectin ≥ 250mcg/g stool at screening.
Outcome measures
| Measure |
Methotrexate Maintenance (Week 17-48)
n=33 Participants
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=32 Participants
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Methotrexate: Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|
|
Calprotectin Levels < 50 mcg/g Stool in Patients in Remission at Week 48 With Calprotectin Levels ≥ 250 mcg/g Stool at Screening
|
2 Participants
|
2 Participants
|
Adverse Events
Induction Period (Week 1-16)
Serious events: 15 serious events
Other events: 69 other events
Deaths: 0 deaths
Methotrexate Maintenance (Week 17-48)
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
Placebo Maintenance (Week 17-48)
Serious events: 1 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Induction Period (Week 1-16)
n=179 participants at risk
Steroid taper for 12 weeks and 25 mg MTX sq once weekly + 1 mg folic acid daily
|
Methotrexate Maintenance (Week 17-48)
n=44 participants at risk
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=40 participants at risk
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|---|
|
Gastrointestinal disorders
Hospitalization
|
8.4%
15/179 • Number of events 18 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
0.00%
0/44 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
2.5%
1/40 • Number of events 1 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
Other adverse events
| Measure |
Induction Period (Week 1-16)
n=179 participants at risk
Steroid taper for 12 weeks and 25 mg MTX sq once weekly + 1 mg folic acid daily
|
Methotrexate Maintenance (Week 17-48)
n=44 participants at risk
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
Placebo Maintenance (Week 17-48)
n=40 participants at risk
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Discomfort
|
6.1%
11/179 • Number of events 13 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
29.5%
13/44 • Number of events 13 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
25.0%
10/40 • Number of events 10 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Gastrointestinal disorders
Diarrhea
|
4.5%
8/179 • Number of events 8 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
31.8%
14/44 • Number of events 14 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
32.5%
13/40 • Number of events 13 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Nervous system disorders
Dizziness
|
5.6%
10/179 • Number of events 11 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
2.3%
1/44 • Number of events 1 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
7.5%
3/40 • Number of events 3 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Hepatobiliary disorders
Elevated liver enzymes
|
3.4%
6/179 • Number of events 6 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
11.4%
5/44 • Number of events 5 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
7.5%
3/40 • Number of events 3 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Nervous system disorders
Fatigue
|
10.6%
19/179 • Number of events 20 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
11.4%
5/44 • Number of events 5 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
12.5%
5/40 • Number of events 5 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Gastrointestinal disorders
Nausea
|
20.1%
36/179 • Number of events 39 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
29.5%
13/44 • Number of events 16 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
12.5%
5/40 • Number of events 7 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.1%
2/179 • Number of events 2 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
0.00%
0/44 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
5.0%
2/40 • Number of events 2 • The adverse events were collected from each study participant from the screening visit until last study visit , which could be early termination or the last visit of the study (week 48).
|
Additional Information
Dr. Hans Herfarth
University of North Carolina, Chapel Hill, NC
Phone: 9199666806
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place