Ignite Creation Date:
2024-05-05 @ 5:05 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00385736
Status:
COMPLETED
Last Update Posted:
2011-04-11
First Post:
2006-10-09
Brief Title:
Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Acute Ulcerative Colitis
Sponsor:
Abbott
Organization:
Abbott
Study Overview
Official Title:
A Multicenter Randomized Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Status:
COMPLETED
Status Verified Date:
2011-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The objective of this study is to assess the efficacy and safety of adalimumab for the induction of clinical remission in subjects with moderately to severely active ulcerative colitis
Detailed Description:
This was a Phase 3 multicenter randomized double-blind DB placebo-controlled trial designed to evaluate the efficacy and safety of the human anti-TNF monoclonal antibody adalimumab for the induction of clinical remission in participants with moderately to severely active ulcerative colitis UC
Adult participants with moderate to severe UC Mayo score of 6 to 12 points with endoscopy subscore of 2 to 3 points confirmed by colonoscopy with biopsy or by flexible sigmoidoscopy with biopsy were enrolled at 80 sites worldwide The study enrolled 576 participants including 186 participants under the original protocol and protocol Amendments 1 and 2 and 390 participants under protocol Amendments 3 and 4
Participants enrolled in the study prior to Amendment 3 were randomized in a 11 ratio to receive adalimumab or placebo during the 12-week DB induction period Participants received 4 injections of adalimumab 40 mg 160 mg or 4 injections of placebo at Baseline Week 0 followed by 2 injections of adalimumab 40 mg 80 mg or 2 injections of placebo at Week 2 followed by 1 injection of adalimumab 40 mg or placebo at Weeks 4 and 6 At Week 8 participants randomized to placebo received 4 injections of adalimumab 40 mg 160 mg followed by 2 injections of adalimumab 40 mg 80 mg at Week 10 Participants randomized to adalimumab received 3 injections of placebo and 1 injection of adalimumab 40 mg at Week 8 and 1 injection of placebo and 1 injection of adalimumab 40 mg at Week 10 All participants continued to receive 1 injection of open-label OL adalimumab 40 mg every other week beginning at Week 12 up to Week 52 or the early termination visit Starting at Week 14 participants who had inadequate responses to treatment as defined using partial Mayo scores were permitted to dose escalate to adalimumab 40 mg weekly Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator
In August 2007 the study design was amended to incorporate an additional adalimumab induction dosing arm of 8040 mg Earlier that year both 16080-mg and 8040-mg induction regimens had been approved in the EU as induction treatment for Crohns disease The adalimumab induction dosing regimen of 8040 mg was therefore included so that both of these approved induction regimens would be evaluated for the induction of remission of UC
Participants enrolled in the study after Amendment 3 were randomized in a 111 ratio to receive adalimumab 1 of 2 regimens or placebo during the 8-week DB induction period Participants received DB therapy from Baseline until Week 8 and OL therapy from Week 8 until the end of the study In the first adalimumab dosing arm adalimumab 8040 participants received 2 injections of adalimumab 40 mg 80 mg and 2 injections of placebo at Baseline followed by 1 injection of adalimumab 40 mg and 1 injection of placebo at Week 2 and 1 injection of adalimumab 40 mg every other week thereafter In the second adalimumab DB induction dosing arm adalimumab 16080 participants received 4 injections of adalimumab 40 mg 160 mg at Baseline followed by 2 injections of adalimumab 40 mg 80 mg at Week 2 and 1 injection of adalimumab 40 mg every other week thereafter Participants randomized to placebo received 4 injections of placebo at Baseline followed by 2 injections of placebo at Week 2 and 1 injection of placebo at Weeks 4 and 6 Beginning at Week 8 but after the Week 8 study assessments had been completed all participants received 1 injection of OL adalimumab 40 mg every other week until Week 52 or early termination Starting at Week 12 participants who had inadequate responses to treatment as defined using partial Mayo scores were permitted to dose escalate to adalimumab 40 mg weekly Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator
For the analysis of efficacy parameters during the DB Period through Week 8 only participants randomized under Protocol Amendment 3 or later were considered Efficacy Analysis Set - Induction in the participant flow For the analysis of efficacy parameters during the OL Period through Week 52 all randomized participants under any version of the protocol who received at least 1 dose of study drug were considered Efficacy Analysis Set - Maintenance in the participant flow For the analysis of safety parameters all participants who received at least 1 dose of study drug were considered Safety Analysis Set in the participant flow
Twelve ranked secondary variables during the DB Period through Week 8 were to be tested in a hierarchical order to account for multiple testing These variables are identified as Ranked Secondary Endpoints in the results section below Additionally non-ranked secondary variables during the OL Period through Week 52 were tested and are presented after the ranked secondary endpoints in the results section below
Adult participants with moderate to severe UC Mayo score of 6 to 12 points with endoscopy subscore of 2 to 3 points confirmed by colonoscopy with biopsy or by flexible sigmoidoscopy with biopsy were enrolled at 80 sites worldwide The study enrolled 576 participants including 186 participants under the original protocol and protocol Amendments 1 and 2 and 390 participants under protocol Amendments 3 and 4
Participants enrolled in the study prior to Amendment 3 were randomized in a 11 ratio to receive adalimumab or placebo during the 12-week DB induction period Participants received 4 injections of adalimumab 40 mg 160 mg or 4 injections of placebo at Baseline Week 0 followed by 2 injections of adalimumab 40 mg 80 mg or 2 injections of placebo at Week 2 followed by 1 injection of adalimumab 40 mg or placebo at Weeks 4 and 6 At Week 8 participants randomized to placebo received 4 injections of adalimumab 40 mg 160 mg followed by 2 injections of adalimumab 40 mg 80 mg at Week 10 Participants randomized to adalimumab received 3 injections of placebo and 1 injection of adalimumab 40 mg at Week 8 and 1 injection of placebo and 1 injection of adalimumab 40 mg at Week 10 All participants continued to receive 1 injection of open-label OL adalimumab 40 mg every other week beginning at Week 12 up to Week 52 or the early termination visit Starting at Week 14 participants who had inadequate responses to treatment as defined using partial Mayo scores were permitted to dose escalate to adalimumab 40 mg weekly Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator
In August 2007 the study design was amended to incorporate an additional adalimumab induction dosing arm of 8040 mg Earlier that year both 16080-mg and 8040-mg induction regimens had been approved in the EU as induction treatment for Crohns disease The adalimumab induction dosing regimen of 8040 mg was therefore included so that both of these approved induction regimens would be evaluated for the induction of remission of UC
Participants enrolled in the study after Amendment 3 were randomized in a 111 ratio to receive adalimumab 1 of 2 regimens or placebo during the 8-week DB induction period Participants received DB therapy from Baseline until Week 8 and OL therapy from Week 8 until the end of the study In the first adalimumab dosing arm adalimumab 8040 participants received 2 injections of adalimumab 40 mg 80 mg and 2 injections of placebo at Baseline followed by 1 injection of adalimumab 40 mg and 1 injection of placebo at Week 2 and 1 injection of adalimumab 40 mg every other week thereafter In the second adalimumab DB induction dosing arm adalimumab 16080 participants received 4 injections of adalimumab 40 mg 160 mg at Baseline followed by 2 injections of adalimumab 40 mg 80 mg at Week 2 and 1 injection of adalimumab 40 mg every other week thereafter Participants randomized to placebo received 4 injections of placebo at Baseline followed by 2 injections of placebo at Week 2 and 1 injection of placebo at Weeks 4 and 6 Beginning at Week 8 but after the Week 8 study assessments had been completed all participants received 1 injection of OL adalimumab 40 mg every other week until Week 52 or early termination Starting at Week 12 participants who had inadequate responses to treatment as defined using partial Mayo scores were permitted to dose escalate to adalimumab 40 mg weekly Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator
For the analysis of efficacy parameters during the DB Period through Week 8 only participants randomized under Protocol Amendment 3 or later were considered Efficacy Analysis Set - Induction in the participant flow For the analysis of efficacy parameters during the OL Period through Week 52 all randomized participants under any version of the protocol who received at least 1 dose of study drug were considered Efficacy Analysis Set - Maintenance in the participant flow For the analysis of safety parameters all participants who received at least 1 dose of study drug were considered Safety Analysis Set in the participant flow
Twelve ranked secondary variables during the DB Period through Week 8 were to be tested in a hierarchical order to account for multiple testing These variables are identified as Ranked Secondary Endpoints in the results section below Additionally non-ranked secondary variables during the OL Period through Week 52 were tested and are presented after the ranked secondary endpoints in the results section below
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2006-002781-20 | EUDRACT_NUMBER | None | None |