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

NCT00385736 | Completed Phase 3 Results

• 2 other identifiers: M06-8262006-002781-20
• Study Type: interventional
• Target: 576
• Locations: 13 countries
• Sites: 80

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.

Conditions

Ulcerative Colitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Week 8

Secondary Outcomes (21)

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

  Week 8

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

  Week 8

• 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

• 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

• 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

Study Arms (3)

Adalimumab 80/40

EXPERIMENTAL

Biological: adalimumab

Adalimumab 160/80/40

EXPERIMENTAL

Biological: adalimumab

Placebo

PLACEBO COMPARATOR

Biological: placebo

Interventions

adalimumab BIOLOGICAL

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.

Also known as: ABT-D2E7, Humira

Adalimumab 80/40

placebo BIOLOGICAL

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).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants \>= 18 years of age
• Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline
• 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.
• Had to be able to self-administer or has caregiver who can reliably administer subcutaneous injections.
• Had to be able and willing to give written informed consent and to comply with the requirements of this study protocol.
• 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
• 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.
• Judged to be in generally good health as determined by the principal investigator

You may not qualify if:

• History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery.
• Received infliximab or any other anti-TNF agent or any biological therapy in the past.
• Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
• Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline.
• Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
• 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.
• Current diagnosis of fulminant colitis and/or toxic megacolon.
• Participants with disease limited to the rectum (ulcerative proctitis).
• Current diagnosis of indeterminate colitis.
• Current diagnosis and/or history of Crohn's disease.
• Currently receiving total parenteral nutrition.
• Discontinued use of azathioprine or 6-MP within 28 days of Baseline.
• Discontinued use of corticosteroid within 14 days of Baseline.
• 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.
• Participants with positive Clostridium difficile stool assay.

Sponsors & Collaborators

• Abbott: lead

Study Sites (80)

Site Ref # / Investigator 2080

Birmingham, Alabama, 35209, United States

Location

Site Ref # / Investigator 6034

Mobile, Alabama, 36617, United States

Location

Site Ref # / Investigator 5100

Fayetteville, Arkansas, 72703, United States

Location

Site Ref # / Investigator 5390

Orange, California, 92868, United States

Location

Site Ref # / Investigator 5392

San Diego, California, 92123, United States

Location

Site Ref # / Investigator 2245

Bridgeport, Connecticut, 06606, United States

Location

Site Ref # / Investigator 2240

Gainesville, Florida, 32610, United States

Location

Site Ref # / Investigator 2230

South Miami, Florida, 33143, United States

Location

Site Ref # / Investigator 5393

Atlanta, Georgia, 30308, United States

Location

Site Ref # / Investigator 2231

Atlanta, Georgia, 30342, United States

Location

Site Ref # / Investigator 2498

Chicago, Illinois, 60637, United States

Location

Site Ref # / Investigator 2078

Chevy Chase, Maryland, 20815, United States

Location

Site Ref # / Investigator 2238

Silver Springs, Maryland, 20901, United States

Location

Site Ref # / Investigator 1971

Boston, Massachusetts, 02114, United States

Location

Site Ref # / Investigator 2246

Rochester, Minnesota, 55905, United States

Location

Site Ref # / Investigator 2243

Kansas City, Missouri, 64131, United States

Location

Site Ref # / Investigator 2247

Mexico, Missouri, 65265, United States

Location

Site Ref # / Investigator 2233

Lincoln, Nebraska, 68503, United States

Location

Site Ref # / Investigator 2236

Cedar Knolls, New Jersey, 07927, United States

Location

Site Ref # / Investigator 2072

New York, New York, 10028, United States

Location

Site Ref # / Investigator 2241

Charlotte, North Carolina, 28211, United States

Location

Site Ref # / Investigator 2232

Raleigh, North Carolina, 27612, United States

Location

Site Ref # / Investigator 11801

Wilmington, North Carolina, 28403, United States

Location

Site Ref # / Investigator 2074

Cincinnati, Ohio, 45219, United States

Location

Site Ref # / Investigator 2126

Cleveland, Ohio, 44106-5066, United States

Location

Site Ref # / Investigator 6090

Germantown, Tennessee, 38138, United States

Location

Site Ref # / Investigator 2076

Nashville, Tennessee, 37203, United States

Location

Site Ref # / Investigator 2229

Bellevue, Washington, 98004, United States

Location

Site Ref # / Investigator 2077

Milwaukee, Wisconsin, 53215, United States

Location

Site Ref # / Investigator 4936

Graz, 8036, Austria

Location

Site Ref # / Investigator 6224

Hall in Tirol, 6060, Austria

Location

Site Ref # / Investigator 3830

Innsbruck, A-6020, Austria

Location

Site Ref # / Investigator 7508

Linz, A-4010, Austria

Location

Site Ref # / Investigator 3829

Salzburg, A-5020, Austria

Location

Site Ref # / Investigator 4937

Vienna, 1030, Austria

Location

Site Ref # / Investigator 3831

Vienna, 1090, Austria

Location

Site Ref # / Investigator 3861

Bonheiden, 2820, Belgium

Location

Site Ref # / Investigator 3859

Liège, 4000, Belgium

Location

Site Ref # / Investigator 3862

Roeselare, 8800, Belgium

Location

Site Ref # / Investigator 2224

Calgary, Alberta, T2N 4Z6, Canada

Location

Site Ref # / Investigator 2227

Edmonton, Alberta, T6G 2X8, Canada

Location

Site Ref # / Investigator 2226

Vancouver, British Columbia, V6Z-2K5, Canada

Location

Site Ref # / Investigator 2223

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Site Ref # / Investigator 2138

Toronto, Ontario, M3N 2V7, Canada

Location

Site Ref # / Investigator 3858

Brno, 62500, Czechia

Location

Site Ref # / Investigator 3856

Olomouc, 77520, Czechia

Location

Site Ref # / Investigator 3857

Ostrava, 708 52, Czechia

Location

Site Ref # / Investigator 3854

Prague, 118 83, Czechia

Location

Site Ref # / Investigator 3855

Prague, 17000, Czechia

Location

Site Ref # / Investigator 3832

Berlin, 13353, Germany

Location

Site Ref # / Investigator 13983

Essen, D-45239, Germany

Location

Site Ref # / Investigator 3834

Jena, 07747, Germany

Location

Site Ref # / Investigator 3833

Kiel, 24105, Germany

Location

Site Ref # / Investigator 3878

Mainz, 55131, Germany

Location

Site Ref # / Investigator 3897

Munich, 81377, Germany

Location

Site Ref # / Investigator 3852

Budapest, H-1076, Hungary

Location

Site Ref # / Investigator 3850

Budapest, H-1125, Hungary

Location

Site Ref # / Investigator 3849

Győr, H-9024, Hungary

Location

Site Ref # / Investigator 3876

Bologna, 40138, Italy

Location

Site Ref # / Investigator 3848

Milan, 20157, Italy

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Site Ref # / Investigator 3845

Palermo, 90146, Italy

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Site Ref # / Investigator 6232

Rome, 00133, Italy

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Site Ref # / Investigator 3846

Rome, 00152, Italy

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Site Ref # / Investigator 3873

Eindhoven, 5623 EJ, Netherlands

Location

Site Ref # / Investigator 3875

Leiden, 2333 ZA, Netherlands

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Site Ref # / Investigator 8061

Lodz, 90-153, Poland

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Site Ref # / Investigator 13804

Sopot, 81-756, Poland

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Site Ref # / Investigator 8055

Warsaw, 02-507, Poland

Location

Site Ref # / Investigator 2392

Ponce, 00717, Puerto Rico

Location

Site Ref # / Investigator 2393

San Juan, 00936-5067, Puerto Rico

Location

Site Ref # / Investigator 3839

Banská Bystrica, 97 401, Slovakia

Location

Site Ref # / Investigator 3838

Bratislava, 811 07, Slovakia

Location

Site Ref # / Investigator 3841

Bratislava, 833 05, Slovakia

Location

Site Ref # / Investigator 3842

Nitra, 94 901, Slovakia

Location

Site Ref # / Investigator 14721

Prešov, 08001, Slovakia

Location

Site Ref # / Investigator 14521

Trenčín, 91101, Slovakia

Location

Site Ref # / Investigator 3840

Trnava, 917 01, Slovakia

Location

Site Ref # / Investigator 8503

Gothenburg, 41345, Sweden

Location

Site Ref # / Investigator 8504

Linköping, 581 85, Sweden

Location

Site Ref # / Investigator 8502

Lund, 22185, Sweden

Location

Related Publications (4)

• Ryan C, Sobell JM, Leonardi CL, Lynde CW, Karunaratne M, Valdecantos WC, Hendrickson BA. Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis. Am J Clin Dermatol. 2018 Jun;19(3):437-447. doi: 10.1007/s40257-017-0341-6.

  PMID: 29380251 DERIVED

• Feagan BG, Sandborn WJ, Lazar A, Thakkar RB, Huang B, Reilly N, Chen N, Yang M, Skup M, Mulani P, Chao J. Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis. Gastroenterology. 2014 Jan;146(1):110-118.e3. doi: 10.1053/j.gastro.2013.09.032. Epub 2013 Sep 22.

  PMID: 24067881 DERIVED

• Reinisch W, Sandborn WJ, Panaccione R, Huang B, Pollack PF, Lazar A, Thakkar RB. 52-week efficacy of adalimumab in patients with moderately to severely active ulcerative colitis who failed corticosteroids and/or immunosuppressants. Inflamm Bowel Dis. 2013 Jul;19(8):1700-9. doi: 10.1097/MIB.0b013e318281f2b7.

  PMID: 23665965 DERIVED

• Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5.

  PMID: 21209123 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Roopal Thakkar, MD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 9, 2006
• First Posted: October 11, 2006
• Study Start: November 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: March 1, 2010
• Last Updated: April 11, 2011
• Results First Posted: May 27, 2010

Record last verified: 2011-04

Locations

US (29); IT (5); CA (5); NL (2); HU (3); CZ (5); BE (3); DE (6); PL (3); PR (2); SL (7); AU (7); SE (3)