Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Acute Ulcerative Colitis

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

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00385736

Enrollment

576

Registered

2006-10-11

Start date

2006-11-30

Completion date

2010-03-31

Last updated

2011-04-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ulcerative Colitis

Keywords

Moderate to Severe Ulcerative Colitis, Double-blind, Adalimumab, Induction of Clinical Remission

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 1:1 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 80/40 mg. Earlier that year, both 160/80-mg and 80/40-mg induction regimens had been approved in the EU as induction treatment for Crohn's disease. The adalimumab induction dosing regimen of 80/40 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 1:1:1 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 80/40), 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 160/80), 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.

Interventions

BIOLOGICALadalimumab

Prefilled syringe, 40 mg (loading dose then every other week dosing). 80 mg at Week 0, 40 mg at Week 2, and 40 mg every other week starting at Week 4.

BIOLOGICALplacebo

Placebo for 40 mg syringe. Matching placebo for loading dose and every other week dosing. Subjects received placebo at Weeks 0, 2, 4, and 6, followed by 160 mg adalimumab at Week 8, 80 mg adalimumab at Week 10, and 40 mg adalimumab eow thereafter (prior to Amendment 3) or 40 mg adalimumab eow starting at Week 8 (after Amendment 3).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

The following eligibility criteria applied to participants enrolled following Amendment 3 to the study protocol. Inclusion Criteria: 1. Male and female participants \>= 18 years of age 2. Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline 3. Diagnosis of active ulcerative colitis confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection 4. Active UC with a Mayo score of 6 to 12 points and endoscopy subscore of 2 to 3 points, despite concurrent treatment with at least 1 of the following (oral corticosteroids or immunosuppressants or both as defined below): * Stable oral corticosteroid dose (prednisone dose of \>= 20 mg/day or equivalent) for at least 14 days prior to Baseline or stable oral corticosteroid dose (prednisone of \< 20 mg/day) for at least 40 days prior to Baseline. and/or * At least a consecutive 90 day course of azathioprine or 6-mercaptopurine (6 MP) prior to Baseline, with a dose of azathioprine \>= 1.5 mg/kg/day or 6 MP \>= 1 mg/kg/day (rounded to the nearest available tablet formulation), or a dose that is the highest tolerated by the participant (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Participant was to be on a stable dose for at least 28 days prior to Baseline. Concurrent therapy was not required for participants who were previously treated with corticosteroids or immunosuppressants (azathioprine or 6-MP) during the previous 5 years and, in the judgment of the investigator, have failed to respond to or could not tolerate their treatment. 5. Had to be able to self-administer or has caregiver who can reliably administer subcutaneous injections. 6. Had to be able and willing to give written informed consent and to comply with the requirements of this study protocol. 7. Female had to be either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. Examples of approved methods of birth control included the following: * Condoms, sponge, foams, jellies, diaphragm or intrauterine device * Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug administration * A vasectomized partner 8. The results of the serum pregnancy test performed at the Screening Visit and urine pregnancy test performed at the Baseline Visit had to be negative. 9. Judged to be in generally good health as determined by the principal investigator

Exclusion criteria

1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery. 2. Received infliximab or any other anti-TNF agent or any biological therapy in the past. 3. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study. 4. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline. 5. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 6. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening endoscopy and during the remainder of the Screening Period. 7. Current diagnosis of fulminant colitis and/or toxic megacolon. 8. Participants with disease limited to the rectum (ulcerative proctitis). 9. Current diagnosis of indeterminate colitis. 10. Current diagnosis and/or history of Crohn's disease. 11. Currently receiving total parenteral nutrition. 12. Discontinued use of azathioprine or 6-MP within 28 days of Baseline. 13. Discontinued use of corticosteroid within 14 days of Baseline. 14. Participants using aminosalicylates for less than 90 days prior to Baseline, not on a stable dose for at least 28 days prior to Baseline, or discontinued use within 28 days of Baseline. 15. Participants with positive Clostridium difficile stool assay. 16. Infections requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to Baseline or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to Baseline. 17. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy/flexible sigmoidoscopy showed evidence of dysplasia or a malignancy, the participant was not to be enrolled in the study. 18. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus, immunodeficiency syndrome, central nervous system demyelinating disease, or untreated tuberculosis (TB). 19. Female participants who was pregnant or breast-feeding or considering becoming pregnant during the study. There should be at least a 150-day period between the last dose of study drug and either conception or initiation of breast-feeding in women of childbearing potential. 20. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable ischemic heart disease, moderate to severe congestive heart failure, recent cerebrovascular accident and any other condition, which in the opinion of the investigator, would put the participant at risk by participation in the protocol. 21. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever is longer). 22. History of clinically significant drug or alcohol abuse during the previous year. 23. Participants with known hypersensitivity to the excipients of adalimumab as stated in the label. 24. Participants with any prior exposure to Tysabri® (natalizumab). 25. Participants currently taking both budesonide and prednisone (or equivalent) simultaneously.

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Participants With Clinical Remission Per Mayo Score at Week 8	Week 8	Clinical remission per Mayo score is defined as a total Mayo score \<= 2 and no individual subscore \> 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Secondary

Measure	Time frame	Description
Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	Mucosal healing is defined as Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration)
Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed
Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject's performance status. Possible scores range from 0-3 as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3)
Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	Stool Frequency Subscore ranges from 0-3 as follows: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal
Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	Clinical response per Mayo score is defined as a decrease in Mayo score of \>= 3 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	Mucosal healing defined as Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration)
Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed
Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject's performance status. Possible scores range from 0-3 as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3)
Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	Stool Frequency Subscore ranges from 0-3 as follows: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal
Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) defined as a \>= 16-point increase from Baseline in total IBDQ score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).
Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Week 8	Clinical response per Mayo score is defined as a decrease in Mayo score of \>= 3 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Proportion of Participants With Clinical Remission Per Mayo Score at Week 52	Week 52	Clinical remission per Mayo score is defined as a total Mayo score \<= 2 and no individual subscore \> 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Proportion of Participants With Clinical Remission Per Partial Mayo Score at Week 52	Week 52	Clinical remission per partial Mayo score is defined as a partial Mayo score \<= 2 and no individual subscore \> 1. The partial Mayo score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Proportion of Participants With Clinical Response Per Mayo Score at Week 52	Week 52	Clinical response per Mayo score is defined as a decrease in Mayo score of \>= 3 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Proportion of Participants With Clinical Response Per Partial Mayo Score at Week 52	Week 52	Clinical response per partial Mayo score is defined as a decrease in partial Mayo score of \>= 2 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The partial Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Proportion of Participants With Mucosal Healing at Week 52	Week 52	Mucosal healing is defined as Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration)
Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 52	Week 52	Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed
Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 52	Week 52	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject's performance status. Possible scores range from 0-3 as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3)
Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 52	Week 52	Stool Frequency Subscore ranges from 0-3 as follows: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal
Proportion of Participants With Clinical Remission Per Mayo Score at Week 52 Among Participants Who Were Systemic Corticosteroid-free at Week 52	Week 52	Clinical remission per Mayo score is defined as a total Mayo score \<= 2 and no individual subscore \> 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).
Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).	Week 8	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) defined as a \>= 16-point increase from Baseline in total IBDQ score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).

Countries

Austria, Belgium, Canada, Czechia, Germany, Hungary, Italy, Netherlands, Poland, Puerto Rico, Slovakia, Sweden, United States

Participant flow

Participants by arm

Arm	Count
Placebo Treatment group received placebo at Weeks 0, 2, 4, and 6, followed by 160 mg adalimumab at Week 8, 80 mg adalimumab at Week 10, and 40 mg adalimumab thereafter (prior to Amendment 3) or 40 mg adalimumab eow starting at Week 8 (after Amendment 3).	130
Adalimumab 80/40 Treatment group received 80 mg at Week 0, 40 mg at Week 2, and 40 mg every other week starting at Week 4.	130
Adalimumab 160/80/40 Treatment group received 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week starting at Week 4.	130
Total	390

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Efficacy Analysis Set - Induction	Adverse Event	5	6	4
Efficacy Analysis Set - Induction	Lack of Efficacy	4	2	1
Efficacy Analysis Set - Induction	Lost to Follow-up	0	2	0
Efficacy Analysis Set - Induction	Other	0	0	1
Efficacy Analysis Set - Induction	Protocol Violation	0	0	2
Efficacy Analysis Set - Induction	Withdrawal by Subject	0	2	1
Efficacy Analysis Set - Maintenance	Adverse Event	23	15	23
Efficacy Analysis Set - Maintenance	Lack of Efficacy	38	16	31
Efficacy Analysis Set - Maintenance	Lost to Follow-up	0	2	2
Efficacy Analysis Set - Maintenance	Other	0	4	4
Efficacy Analysis Set - Maintenance	Protocol Violation	2	1	6
Efficacy Analysis Set - Maintenance	Withdrawal by Subject	6	6	14
Safety Analysis Set	Adverse Event	23	15	23
Safety Analysis Set	Lack of Efficacy	38	16	31
Safety Analysis Set	Lost to Follow-up	0	2	2
Safety Analysis Set	Other	1	4	4
Safety Analysis Set	Protocol Violation	2	1	6
Safety Analysis Set	Withdrawal by Subject	6	6	14

Baseline characteristics

Characteristic	Placebo	Adalimumab 80/40	Adalimumab 160/80/40	Total
Age, Categorical <=18 years	1 Participants	2 Participants	1 Participants	4 Participants
Age, Categorical >=65 years	4 Participants	8 Participants	5 Participants	17 Participants
Age, Categorical Between 18 and 65 years	125 Participants	120 Participants	124 Participants	369 Participants
Age Continuous	38.9 years STANDARD_DEVIATION 12.68	41.6 years STANDARD_DEVIATION 13.99	38.2 years STANDARD_DEVIATION 13.46	39.5 years STANDARD_DEVIATION 13.43
Region of Enrollment Austria	7 participants	11 participants	5 participants	23 participants
Region of Enrollment Belgium	4 participants	2 participants	2 participants	8 participants
Region of Enrollment Canada	26 participants	25 participants	20 participants	71 participants
Region of Enrollment Czech Republic	23 participants	11 participants	18 participants	52 participants
Region of Enrollment Germany	3 participants	14 participants	9 participants	26 participants
Region of Enrollment Hungary	9 participants	3 participants	7 participants	19 participants
Region of Enrollment Italy	11 participants	6 participants	7 participants	24 participants
Region of Enrollment Netherlands	1 participants	4 participants	0 participants	5 participants
Region of Enrollment Poland	2 participants	2 participants	2 participants	6 participants
Region of Enrollment Slovakia	12 participants	22 participants	13 participants	47 participants
Region of Enrollment Sweden	0 participants	0 participants	6 participants	6 participants
Region of Enrollment United States	32 participants	30 participants	41 participants	103 participants
Sex: Female, Male Female	48 Participants	52 Participants	47 Participants	147 Participants
Sex: Female, Male Male	82 Participants	78 Participants	83 Participants	243 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	34 / 223	30 / 130	34 / 223	210 / 557
serious Total, serious adverse events	17 / 223	5 / 130	9 / 223	76 / 557

Outcome results

Primary

Proportion of Participants With Clinical Remission Per Mayo Score at Week 8

Clinical remission per Mayo score is defined as a total Mayo score \<= 2 and no individual subscore \> 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Time frame: Week 8

Population: All participants enrolled after Amendment 3 to the study protocol (which introduced the adalimumab 80/40 treatment arm) and who received at least 1 dose of study drug were included in this intent-to-treat (ITT) analysis. Nonresponder imputation (NRI) was used.

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Remission Per Mayo Score at Week 8	9.2 Proportion of participants
Adalimumab 80/40	Proportion of Participants With Clinical Remission Per Mayo Score at Week 8	10.0 Proportion of participants
Adalimumab 160/80/40	Proportion of Participants With Clinical Remission Per Mayo Score at Week 8	18.5 Proportion of participants

p-value: 0.031Chi-squared

p-value: 0.833Chi-squared

Secondary

Proportion of Participants With Clinical Remission Per Mayo Score at Week 52

Time frame: Week 52

Population: All randomized participants (enrolled under any version of the protocol) who received at least 1 dose of study drug were included in this intent-to-treat analysis. Nonresponder imputation (NRI) was used; participants who dose escalated to adalimumab 40 mg ew were considered nonresponders after their dose escalation.

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Remission Per Mayo Score at Week 52	24.2 Proportion of participants

Secondary

Proportion of Participants With Clinical Remission Per Mayo Score at Week 52 Among Participants Who Were Systemic Corticosteroid-free at Week 52

Time frame: Week 52

Population: All randomized participants enrolled under any version of the protocol who took systemic corticosteroids (CS) at Baseline, received at least 1 dose of study drug, and were systemic CS-free at Week 52 were included. Nonresponder imputation was used; participants who dose escalated to adalimumab 40 mg ew were considered nonresponders post-escalation.

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Remission Per Mayo Score at Week 52 Among Participants Who Were Systemic Corticosteroid-free at Week 52	41.5 Proportion of participants

Secondary

Proportion of Participants With Clinical Remission Per Partial Mayo Score at Week 52

Clinical remission per partial Mayo score is defined as a partial Mayo score \<= 2 and no individual subscore \> 1. The partial Mayo score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Remission Per Partial Mayo Score at Week 52	28.3 Proportion of participants

Secondary

Proportion of Participants With Clinical Response Per Mayo Score at Week 52

Clinical response per Mayo score is defined as a decrease in Mayo score of \>= 3 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Response Per Mayo Score at Week 52	42.6 Proportion of participants

Secondary

Proportion of Participants With Clinical Response Per Partial Mayo Score at Week 52

Clinical response per partial Mayo score is defined as a decrease in partial Mayo score of \>= 2 points and \>= 30% from Baseline, plus either a decrease in rectal bleeding subscore of \>= 1 point or an absolute rectal bleeding subscore of 0 or 1. The partial Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Time frame: Week 52

Population: All randomized participants (enrolled under any version of the protocol) who received at least 1 dose of study drug were included in this intent-to-treat analysis. Nonresponder imputation (NRI) was used; subjects who dose escalated to adalimumab 40 mg ew were considered nonresponders after their dose escalation.

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Clinical Response Per Partial Mayo Score at Week 52	41.6 Proportion of participants

Secondary

Proportion of Participants With Mucosal Healing at Week 52

Mucosal healing is defined as Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration)

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Mucosal Healing at Week 52	36.5 Proportion of participants

Secondary

Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 52

The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject's performance status. Possible scores range from 0-3 as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3)

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 52	41.7 Proportion of participants

Secondary

Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 52

Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 52	47.0 Proportion of participants

Secondary

Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 52

Stool Frequency Subscore ranges from 0-3 as follows: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal

Time frame: Week 52

Arm	Measure	Value (NUMBER)
Placebo	Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 52	36.5 Proportion of participants

Secondary

Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	37.7 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	36.2 Proportion of participants

p-value: 0.797Chi-squared

Secondary

Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) defined as a \>= 16-point increase from Baseline in total IBDQ score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).	57.7 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).	60.8 Proportion of participants

p-value: 0.614Chi-squared

Secondary

Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).	57.7 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).	53.8 Proportion of participants

p-value: 0.532Chi-squared

Secondary

Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).	44.6 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).	54.6 Proportion of participants

p-value: 0.107Chi-squared

Secondary

Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).	41.5 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).	46.9 Proportion of participants

p-value: 0.382Chi-squared

Secondary

Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	66.2 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	77.7 Proportion of participants

p-value: 0.038Chi-squared

Secondary

Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	46.9 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	60.0 Proportion of participants

p-value: 0.035Chi-squared

Secondary

Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	37.7 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	48.5 Proportion of participants

p-value: 0.08Chi-squared

Secondary

Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).	44.6 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).	51.5 Proportion of participants

p-value: 0.264Chi-squared

Secondary

Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).

Mucosal healing defined as Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration)

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).	41.5 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).	37.7 Proportion of participants

p-value: 0.526Chi-squared

Secondary

Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).

Rectal Bleeding Subscore ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	66.2 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	70.0 Proportion of participants

p-value: 0.506Chi-squared

Secondary

Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).

Time frame: Week 8

Arm	Measure	Value (NUMBER)
Placebo	Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	46.9 Proportion of participants
Adalimumab 80/40	Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	53.8 Proportion of participants

p-value: 0.264Chi-squared

Source: ClinicalTrials.gov · Data processed: Mar 29, 2026

Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Acute Ulcerative Colitis

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Brief summary

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Interventions

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Study design

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Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

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Outcome results

Proportion of Participants With Clinical Remission Per Mayo Score at Week 8

Proportion of Participants With Clinical Remission Per Mayo Score at Week 52

Proportion of Participants With Clinical Remission Per Mayo Score at Week 52 Among Participants Who Were Systemic Corticosteroid-free at Week 52

Proportion of Participants With Clinical Remission Per Partial Mayo Score at Week 52

Proportion of Participants With Clinical Response Per Mayo Score at Week 52

Proportion of Participants With Clinical Response Per Partial Mayo Score at Week 52

Proportion of Participants With Mucosal Healing at Week 52

Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 52

Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 52

Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 52

Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).

Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).

Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).

Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).

Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).

Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).

Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).