Phase 3
Completed N=961
A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis
Colitis, Ulcerative · Inflammatory Bowel Disease
Source: ClinicalTrials.gov NCT02407236 ↗
Enrolled (actual)
961
Serious AEs
7.0%
Results posted
Dec 2019
Primary outcomePrimary: Induction Study - Number of Participants With Clinical Remission at Week 8 (As Per Global Definition) — 17; 50; 50 Participants — p=< 0.001
◆ Published Evidence
Established
38citations · ~19 / year
Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.
Summary
The purpose of this study is to evaluate the efficacy and safety of ustekinumab as intravenous (IV: into the vein) infusion in induction study in participants with moderately to severely active Ulcerative Colitis (UC) and as subcutaneous (SC) administration in maintenance study in participants with moderately to severely active Ulcerative Colitis (UC) who have demonstrated a clinical response to Induction treatment with IV ustekinumab.
Linked Publications (5)
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Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.
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Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.
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Trajectory of fecal lactoferrin for predicting prognosis in ulcerative colitis.
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Clinical Trial: Association Between Early Disease Clearance and Long-Term Outcomes-4-Year Results From the Phase 3 UNIFI Study of Ustekinumab in Ulcerative Colitis.
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Responsiveness of different disease activity indices in moderate-to-severe ulcerative colitis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Induction Study - Number of Participants With Clinical Remission at Week 8 (As Per Global Definition) |
17; 50; 50 | < 0.001 sig |
| PRIMARY Induction Study - Number of Participants With Clinical Remission at Week 8 (As Per US Definition) |
20; 53; 61 | < 0.001 sig |
| PRIMARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 (As Per Global Definition) |
42; 66; 77 | 0.002 sig |
| PRIMARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 (as Per US Definition) |
43; 68; 75 | 0.002 sig |
| SECONDARY Induction Study: Number of Participants With Endoscopic Healing at Week 8 |
44; 84; 87 | — |
| SECONDARY Induction Study: Number of Participants With Clinical Response at Week 8 |
100; 164; 199 | — |
| SECONDARY Induction Study - Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 |
16.1; 33.4; 35.0 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Response up to Week 44 |
78; 117; 125 | — |
| SECONDARY Maintenance Study: Number of Participants With Endoscopic Healing at Week 44 |
50; 75; 90 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission and Not Receiving Concomitant Corticosteroids (Corticosteroid-free Clinical Remission) at Week 44 (As Per Global Definition) |
41; 65; 74 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission and Not Receiving Concomitant Corticosteroids (Corticosteroid-free Clinical Remission) at Week 44 (As Per US Definition) |
42; 67; 72 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission up to Week 44 Among Participants Who Achieved Clinical Remission at Maintenance Study Baseline (As Per Global Definition) |
17; 26; 22 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission up to Week 44 Among Participants Who Achieved Clinical Remission at Maintenance Study Baseline (As Per US Definition) |
16; 32; 27 | — |
| SECONDARY Induction Study - Number of Participants With Mucosal Healing at Week 8 |
28; 64; 58 | — |
| SECONDARY Induction Study - Number of Participants in Clinical Remission With a Rectal Bleeding Subscore of 0 at Week 8 (As Per Global Definition) |
17; 49; 49 | — |
| SECONDARY Induction Study - Number of Participants in Symptomatic Remission at Week 8 |
72; 132; 144 | — |
| SECONDARY Induction Study - Number of Participants in With Normal or Inactive Mucosal Disease at Week 8 |
12; 33; 25 | — |
| SECONDARY Induction Study - Change From Baseline in Mayo Score at Week 8 |
-1.8; -3.2; -3.5 | — |
| SECONDARY Induction Study - Change From Baseline in Partial Mayo Score Through Week 8 |
-1.0; -1.5; -1.6; -1.4; -2.1; -2.5 | — |
| SECONDARY Induction Study - Number of Participants With Individual Mayo Subscore (Stool Frequency) up to Week 8 |
16; 32; 26; 82; 99; 94 | — |
| SECONDARY Induction Study - Number of Participants With Individual Mayo Subscore (Rectal Bleeding) up to Week 8 |
83; 104; 120; 119; 122; 131 | — |
| SECONDARY Induction Study - Number of Participants With Individual Mayo Subscore (Endoscopy Findings) at Week 8 |
12; 33; 25; 32; 51; 62 | — |
| SECONDARY Induction Study - Number of Participants With Individual Mayo Subscore (Physician's Global Assessment) up to Week 8 |
3; 4; 10; 66; 82; 81 | — |
| SECONDARY Induction Study - Number of Participants With Clinical Remission at Week 8 by Biologic Failure (BF) Status (As Per Global Definition) |
2; 19; 21; 15; 31; 29 | — |
| SECONDARY Induction Study - Number of Participants With Clinical Remission at Week 8 by Biologic Failure (BF) Status (As Per US Definition) |
4; 19; 22; 16; 34; 39 | — |
| SECONDARY Induction Study - Number of Participants With Endoscopic Healing at Week 8 by Biologic Failure Status |
11; 30; 35; 33; 54; 52 | — |
| SECONDARY Induction Study - Number of Participants With Clinical Response at Week 8 by Biologic Failure Status |
44; 74; 95; 56; 90; 104 | — |
| SECONDARY Induction Study: Number of Participants in Remission Based on Stool Frequency Subscore of 0 or 1, Rectal Bleeding Subscore of 0, and Endoscopy Subscore of 0 or 1 at Week 8 (US Specific) |
25; 60; 67 | — |
| SECONDARY Induction Study: Number of Participants in Remission Based on Stool Frequency Subscore of 0, Rectal Bleeding Subscore of 0, and Endoscopy Subscore of 0 or 1 at Week 8 (US Specific) |
10; 35; 29 | — |
| SECONDARY Induction Study - Change From Baseline in C-reactive Protein (CRP) Concentration Through Week 8 |
-0.01; -0.75; -0.92; -0.18; -1.08; -1.94 | — |
| SECONDARY Induction Study - Number of Participants With Normalized CRP (<=3 mg/L) up to Week 8 Among Participants With Abnormal CRP (>3 mg/L) at Baseline |
36; 54; 58; 41; 70; 75 | — |
| SECONDARY Induction Study - Change From Baseline in Fecal Lactoferrin Concentration Through Week 8 |
0.00; -4.67; -24.06; 0.00; -29.26; -69.51 | — |
| SECONDARY Induction Study - Number of Participants With Normalized Fecal Lactoferrin (<=7.24 mcg/g) up to Week 8 Among Participants With Abnormal Fecal Lactoferrin (>7.24 mcg/g) at Baseline |
16; 17; 15; 16; 37; 33 | — |
| SECONDARY Induction Study - Change From Baseline in Fecal Calprotectin Concentration Through Week 8 |
0.00; -29.00; -127.00; -2.00; -223.00; -485.50 | — |
| SECONDARY Induction Study - Number of Participants With Normalized Fecal Calprotectin (<=250 mg/kg) up to Week 8 Among Participants With Abnormal Fecal Calprotectin (>250 mg/kg) at Baseline |
20; 37; 37; 25; 45; 47 | — |
| SECONDARY Induction Study - Number of Participants With a >20-point Improvement From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 |
118; 196; 200 | — |
| SECONDARY Induction Study - Change From Baseline in IBDQ Dimension Scores at Week 8 |
5.9; 12.5; 12.7; 5.3; 10.1; 11.2 | — |
| SECONDARY Induction Study - Change From Baseline in 36-Item Short-Form (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Week 8 |
2.1; 4.7; 5.2; 2.2; 5.3; 5.1 | — |
| SECONDARY Induction Study - Change From Baseline in Individual Subscales of 36-Item Short-Form (SF-36) at Week 8 |
1.7; 3.0; 3.4; 2.4; 5.9; 6.1 | — |
| SECONDARY Induction Study - Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Health Questionnaire Index Score at Week 8 |
0.04; 0.09; 0.11 | — |
| SECONDARY Induction Study - Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Health State Visual Analog Scale (VAS) Score at Week 8 |
5.71; 13.64; 13.51 | — |
| SECONDARY Induction Study - Percentage of Participants With Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Score at Week 8 |
18.0; 16.3; 24.2; 71.9; 71.8; 66.8 | — |
| SECONDARY Maintenance Study - Change From Maintenance Baseline in Mayo Score at Week 44 |
1.6; 0.1; -0.5 | — |
| SECONDARY Maintenance Study - Change From Induction Baseline in Mayo Score at Week 44 |
-3.3; -5.0; -5.6 | — |
| SECONDARY Maintenance Study - Number of Participants With Individual Mayo Subscore (Stool Frequency) up to Week 44 |
56; 61; 58; 91; 76; 86 | — |
| SECONDARY Maintenance Study - Number of Participants With Individual Mayo Subscore (Rectal Bleeding) up to Week 44 |
149; 148; 143; 20; 23; 29 | — |
| SECONDARY Maintenance Study - Number of Participants With Individual Mayo Subscore (Endoscopy Findings) at Week 44 |
33; 43; 52; 21; 37; 42 | — |
| SECONDARY Maintenance Study - Number of Participants With Individual Mayo Subscore (Physician's Global Assessment) up to Week 44 |
62; 61; 59; 100; 99; 105 | — |
| SECONDARY Maintenance Study - Change From Maintenance Baseline in Partial Mayo Score Through Week 44 |
-0.2; -0.3; -0.1; -0.1; -0.3; -0.2 | — |
| SECONDARY Maintenance Study - Change From Induction Baseline in Partial Mayo Score Through Week 44 |
-4.2; -4.5; -4.4; -4.1; -4.5; -4.5 | — |
| SECONDARY Maintenance Study: Number of Participants in Remission Based on Stool Frequency Subscore of 0 or 1, Rectal Bleeding Subscore of 0, and Endoscopy Subscore of 0 or 1 at Week 44 |
49; 70; 84 | — |
| SECONDARY Maintenance Study: Number of Participants in Remission Based on Stool Frequency Subscore of 0, Rectal Bleeding Subscore of 0, and Endoscopy Subscore of 0 or 1 at Week 44 |
30; 42; 48 | — |
| SECONDARY Maintenance Study: Number of Participants in Symptomatic Remission at Week 44 |
79; 107; 119 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 by Biologic Failure Status (As Per Global Definition) |
15; 16; 36; 27; 50; 41 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 by Biologic Failure Status (As Per US Definition) |
15; 17; 34; 28; 51; 41 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Response up to Week 44 by Biologic Failure Status |
34; 39; 59; 44; 78; 66 | — |
| SECONDARY Maintenance Study: Number of Participants With Endoscopic Healing at Week 44 by Biologic Failure Status |
20; 18; 41; 30; 57; 49 | — |
| SECONDARY Maintenance Study: Number of Participants With Endoscopic Healing at Week 44 Among Participants Who Had Achieved Endoscopic Healing at Maintenance Baseline |
25; 41; 37 | — |
| SECONDARY Maintenance Study: Number of Participants With Normal or Inactive Mucosal Disease at Week 44 |
32; 41; 51 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 and Not Receiving Concomitant Corticosteroids at Week 44 Among Participants Who Received Concomitant Corticosteroids at Maintenance Baseline (Per Global Definition) |
17; 25; 36 | — |
| SECONDARY Maintenance Study: Number of Participants With Clinical Remission at Week 44 and Not Receiving Concomitant Corticosteroids at Week 44 Among Participants Who Received Concomitant Corticosteroids at Maintenance Baseline (Per US Definition) |
18; 27; 34 | — |
| SECONDARY MS: Change From Maintenance Baseline in Average Daily P.Eq Corticosteroid Dose Through Week 44 Among Participants Who Received Corticosteroids Other Than Budesonide and Beclomethasone Dipropionate at Maintenance Baseline |
-7.4; -7.8; -7.2; -10.8; -11.7; -12.1 | — |
| SECONDARY Maintenance Study: Number of Participants Not Receiving Concomitant Corticosteroids at Week 44 Among Participants Who Received Concomitant Corticosteroids at Maintenance Baseline |
43; 56; 73 | — |
| SECONDARY Maintenance Study: Number of Participants Who Maintained 20-point Improvement From Induction Baseline in IBDQ up to Week 44 Among Participants With a >20-point Improvement in IBDQ at Maintenance Baseline |
64; 95; 102 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in the IBDQ Score at Week 20 and 44 |
-7.0; 0.8; 5.5; -15.1; -3.0; 3.9 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in the IBDQ Dimension Scores at Week 20 and 44 |
-3.2; -0.5; 1.3; -5.7; -1.6; 0.8 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in 36-Item Short-Form (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Weeks 20 and 44 |
-1.2; -0.2; 0.8; -1.7; -0.4; 1.3 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in Individual Subscales of 36-Item Short-Form (SF-36) at Weeks 20 and 44 |
-0.61; -0.01; 0.51; -1.40; -0.44; 0.66 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in EuroQOL-5 Dimensions (EQ-5D) Health Questionnaire Index Score at Weeks 20 and 44 |
-0.036; -0.002; 0.016; -0.048; 0.008; 0.025 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in EuroQOL-5 (EQ-5D) Health State Visual Analog Scale (VAS) Score at Weeks 20 and 44 |
-4.0; -0.3; 2.6; -7.7; -2.2; 2.4 | — |
| SECONDARY Maintenance Study: Percentage of Participants With Change From Maintenance Baseline in EuroQOL-5 (EQ-5D) Dimensions Score at Weeks 20 and 44 |
12.7; 10.5; 13.7; 75.7; 79.1; 78.9 | — |
| SECONDARY Maintenance Study: Number of Participants With Mucosal Healing at Week 44 |
41; 66; 79 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in C-reactive Protein (CRP) Concentration at Weeks 8, 24, and 44 |
0.05; -0.03; -0.04; 0.68; 0.13; -0.03 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in Fecal Lactoferrin Concentration at Weeks 8, 24, and 44 |
0.0; 0.0; -1.4; 2.2; -0.8; -2.3 | — |
| SECONDARY Maintenance Study: Change From Maintenance Baseline in Fecal Calprotectin Concentration at Weeks 8, 24, and 44 |
0.0; -18.5; -31.0; 125.0; -31.5; -46.0 | — |
Eligibility Criteria
Inclusion Criteria
- Has a clinical diagnosis of Ulcerative Colitis (UC) at least 3 months before Screening
- Has moderately to severely active UC, defined as a Baseline (Week 0) Mayo score of 6 to 12, including a Screening endoscopy subscore of the Mayo score greater than or equal to (>=) 2 as determined by a central reading of the video endoscopy
- Have failed biologic therapy, that is, have received treatment with 1 or more tumour necrosis factor (TNF) antagonists or vedolizumab at a dose approved for the treatment of UC, and have a documented history of failure to respond to or tolerate such treatment; OR Be naïve to biologic therapy (TNF antagonists or vedolizumab) or have received biologic therapy but have not demonstrated a history of failure to respond to, or tolerate, a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following: a. Inadequate response to or failure to tolerate current treatment with oral corticosteroids or immunomodulators (6-mercaptopurine [6-MP] or azathioprine [AZA]) OR b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) OR c. History of corticosteroid dependence (that is, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
- Before the first administration of study agent, the following conditions must be met: vedolizumab must have been discontinued for at least 4 months and anti-tumor necrosis factors (TNFs) for at least 8 weeks
Exclusion Criteria
- Has severe extensive colitis and is at imminent risk of colectomy
- Has UC limited to the rectum only or to < 20 centimeters (cm) of the colon
- Presence of a stoma or history of a fistula
- Participants with history of extensive colonic resection (for example, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity
- Participants with history of colonic mucosal dysplasia. Participants will not be excluded from the study because of a pathology finding of "indefinite dysplasia with reactive atypia''
Data sourced from ClinicalTrials.gov (NCT02407236) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.