Trial Outcomes & Findings for Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease (NCT NCT01951326)
NCT ID: NCT01951326
Last Updated: 2020-12-08
Results Overview
Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
331 participants
Primary outcome timeframe
Week 26
Results posted on
2020-12-08
Participant Flow
Participant milestones
| Measure |
RHB-104
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Overall Study
STARTED
|
166
|
165
|
|
Overall Study
COMPLETED
|
87
|
87
|
|
Overall Study
NOT COMPLETED
|
79
|
78
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease
Baseline characteristics by cohort
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
Total
n=331 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.0 years
STANDARD_DEVIATION 12.51 • n=5 Participants
|
39.3 years
STANDARD_DEVIATION 12.56 • n=7 Participants
|
39.1 years
STANDARD_DEVIATION 12.52 • n=5 Participants
|
|
Sex: Female, Male
Female
|
75 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
91 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
189 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
156 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
47 participants
n=5 Participants
|
50 participants
n=7 Participants
|
97 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
18 participants
n=5 Participants
|
20 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Southeast Asia
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
North America
|
92 participants
n=5 Participants
|
83 participants
n=7 Participants
|
175 participants
n=5 Participants
|
|
Baseline Crohn's Disease Activity Index (CDAI) score
|
297.77 units on a scale
STANDARD_DEVIATION 57.023 • n=5 Participants
|
293.44 units on a scale
STANDARD_DEVIATION 53.184 • n=7 Participants
|
295.61 units on a scale
STANDARD_DEVIATION 55.102 • n=5 Participants
|
|
Anti-TNF Use at Baseline
|
37 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 26Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Remission at Week 26
|
61 Participants
|
37 Participants
|
SECONDARY outcome
Timeframe: Week 26Reduction of Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points. Lower CDAI scores indicate a better outcome.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Response at Week 26
|
73 Participants
|
50 Participants
|
SECONDARY outcome
Timeframe: Week 52Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Remission at Week 52
|
47 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: Week 26 through week 52When a subject is in remission with a maximum CDAI score of 149 at every visit from Week 26 through and including Week 52
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Durable Remission Week 26 Through Week 52
|
33 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Week 16Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Remission at Week 16
|
70 Participants
|
48 Participants
|
SECONDARY outcome
Timeframe: Week 52Subjects who are maintained off steroids for a minimum of 3 weeks
Outcome measures
| Measure |
RHB-104
n=57 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=55 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Steroid Free Remission at Week 52
|
11 Participants
|
5 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 52Population: Reached duration of remission (dropped out of remission during the study), n (%): RHB-104 54 (53.5); Placebo: 49 (62.8). Censored (remain in remission during the study), n (%): RHB-104: 47 (46.5); Placebo 29 (37.2)
Number of weeks that a subject is in a state of remission. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
Outcome measures
| Measure |
RHB-104
n=101 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=78 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Duration of Remission
|
27.1 weeks
Interval 16.14 to 46.86
|
16.7 weeks
Interval 10.14 to 30.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 52Population: Reached duration of response (dropped out of response during the study), n (%) RHB-104: 52 (45.2); Placebo: 55 (59.8). Censored (remain in response during the study), n (%): RHB-104: 63 (54.8); Placebo: 37 (40.2)
Number of weeks a subject is in a state of response. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
Outcome measures
| Measure |
RHB-104
n=115 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=92 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Duration of Response
|
40.1 weeks
Interval 22.14 to 52.29
|
22.1 weeks
Interval 12.14 to 32.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 52Population: Number of subjects achieved remission, n (%) RHB-104: 101 (60.8); Placebo 78 (47.3). Censored, n (%): RHB-104: 65 (39.2); Placebo 87 (52.7)
\[Date of first observed remission (CDAI score \< 150) - Date of first dose or date of randomization if not dosed + 1\] / 7 Days. Subjects who never experienced remission during the study are censored at the date of their last CDAI assessment.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Time to Remission
|
12.1 weeks
Interval 8.43 to 12.71
|
19.9 weeks
Interval 13.0 to 52.43
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 52Population: Number of subjects achieved response, n (%): RHB-104: 115 (69.3); Placebo: 92 (55.8); Censored, n (%): RHB-104: 51 (30.7); Placebo: 73 (44.2)
\[Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1\] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Time to Response
|
8.3 weeks
Interval 8.0 to 9.14
|
12.1 weeks
Interval 8.14 to 15.71
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 16 through week 52Remission in a subject from week 16 through week 52.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Durable Remission Week 16 Through Week 52
|
31 Participants
|
14 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 16Reduction of Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points. Lower CDAI scores indicate a better outcome.
Outcome measures
| Measure |
RHB-104
n=166 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Response at Week 16
|
79 Participants
|
60 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 26Change-from-baseline to week 26 in QTcF (based on cardiac safety report)
Outcome measures
| Measure |
RHB-104
n=95 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=104 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Cardiac Safety
|
27.8 ms
Interval 25.91 to 29.74
|
0.2 ms
Interval -1.67 to 2.06
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 52Placebo-corrected change-from-baseline to week 52 in QTcF (based on cardiac safety report)
Outcome measures
| Measure |
RHB-104
n=63 Participants
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=54 Participants
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Cardiac Safety
|
29.8 ms
Interval 27.57 to 32.02
|
-0.8 ms
Interval -3.16 to 1.57
|
Adverse Events
RHB-104
Serious events: 31 serious events
Other events: 115 other events
Deaths: 0 deaths
Placebo
Serious events: 31 serious events
Other events: 90 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
RHB-104
n=166 participants at risk
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 participants at risk
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Cardiac disorders
Cardiac disorders
|
1.2%
2/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.61%
1/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
11.4%
19/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
10.3%
17/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
General disorders
General disorders and administration site conditions
|
0.60%
1/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.00%
0/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
1.2%
2/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.00%
0/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Infections and infestations
Infections and infestations
|
2.4%
4/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
6.1%
10/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.60%
1/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.61%
1/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Investigations
Investigations
|
1.2%
2/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.00%
0/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
0.60%
1/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.00%
0/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.60%
1/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
1.2%
2/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
0.00%
0/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.61%
1/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.61%
1/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Vascular disorders
Vascular disorders
|
1.2%
2/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
0.00%
0/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
Other adverse events
| Measure |
RHB-104
n=166 participants at risk
5 RHB-104 capsules administered orally BID
RHB-104: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
|
Placebo
n=165 participants at risk
5 placebo capsules administered orally BID
Placebo: 5 placebo capsules administered orally BID
|
|---|---|---|
|
Gastrointestinal disorders
Crohn's Disease
|
12.7%
21/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
15.2%
25/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
14.5%
24/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
11.5%
19/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Nausea
|
13.3%
22/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
7.3%
12/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Diarrheoa
|
6.6%
11/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
4.8%
8/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Vomiting
|
7.2%
12/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
4.2%
7/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Abdominal tenderness
|
2.4%
4/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
5.5%
9/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
4.8%
8/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
5.5%
9/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Infections and infestations
Influenza
|
3.6%
6/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
6.1%
10/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Infections and infestations
Viral Upper Respiratory Infections
|
4.2%
7/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
5.5%
9/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Infections and infestations
Clostridium difficile Infection
|
1.8%
3/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
7.3%
12/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Renal and urinary disorders
Chromaturia
|
25.3%
42/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
1.2%
2/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Nervous system disorders
Headache
|
9.6%
16/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
10.3%
17/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.6%
16/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
4.2%
7/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Blood and lymphatic system disorders
Anemia
|
6.0%
10/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
3.6%
6/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
|
Gastrointestinal disorders
Pyrexia
|
5.4%
9/166 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
3.6%
6/165 • Baseline through 30 days after last dose of study drug, or up to 13 months
|
Additional Information
Reza Fathi, Senior VP Research and Development
RedHill Biopharma
Phone: 972-(0)3-541-3131
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place