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

NCT00408629 | Completed Phase 3 Results DMC

• 2 other identifiers: M06-8272006-002782-40
• Study Type: interventional
• Target: 518
• Locations: 17 countries
• Sites: 101

Brief Summary

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of the human anti-tumor necrosis factor (TNF) monoclonal antibody adalimumab (ADA) in patients with moderately to severely active ulcerative colitis (UC).

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Adalimumab; TNF Antagonist; Mayo Score

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8

  Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 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 (SFS), Rectal Bleeding Subscore (RBS), Endoscopy Subscore, and Physician's Global Assessment Subscore (PGA), each of which ranges from 0 (normal) to 3 (severe disease).

  Week 8

• Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 52

  Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 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: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).

  Week 52

Secondary Outcomes (15)

• Proportion of Participants Who Achieved Sustained Clinical Remission Per Mayo Score at Both Week 8 and Week 52

  Week 8, Week 52

• Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 8

  Week 8

• Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 52

  Week 52

• Proportion of Participants Who Achieved Sustained Clinical Response Per Mayo Score at Both Week 8 and Week 52

  Week 8, Week 52

• Proportion of Participants Who Achieved Mucosal Healing at Week 8

  Week 8

Study Arms (2)

adalimumab group

EXPERIMENTAL

Biological: adalimumab

placebo group

EXPERIMENTAL

Biological: placebo

Interventions

adalimumab BIOLOGICAL

Prefilled syringe, 40 mg, 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week between Weeks 4 and 50.

Also known as: ABT-D2E7, Humira

adalimumab group

placebo BIOLOGICAL

Matching Placebo for prefilled syringe, 40 mg,

placebo group

Eligibility Criteria

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

You may qualify if:

• Participants \>=18 years of age and in good health (Investigator discretion) with a recent stable medical history
• Diagnosis of UC 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 \>= 20 mg/day or equivalent) for at least 14 days prior to Baseline or maintenance, corticosteroid dose (prednisone \< 20 mg/day or equivalent) for at least 40 days prior to Baseline
• and/or
• At least a 90 day course of azathioprine (AZA) or 6-mercaptopurine (6-MP) prior to Baseline, with a dose of AZA \>= 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 must 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 (AZA or 6-MP) during the past 5 years and in the judgment of the Investigator have failed to respond to, or could not tolerate, their treatment.
• Participants may have been included if they had previously used an anti-tumor necrosis factor (TNF) agent (except ADA) and discontinued its use due to a loss of response or intolerance to the agent.
• Had to be able to self-administer or had caregiver who could reliably administer subcutaneous (SC) injections.
• Had to be able and willing to give written informed consent and to comply with the requirements of the 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 the 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, 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 must have been negative.
• Judged to be in generally good health as determined by the Investigator

You may not qualify if:

• History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC, or planned bowel surgery.
• Received previous treatment with ADA or previous participation in an ADA clinical study.
• Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of Baseline.
• Received intravenous (IV) corticosteroids within 14 days of Screening or during the Screening Period.
• Received therapeutic enema or suppository, other than required for endoscopy, within 14 days of the Screening endoscopy and during the remainder of the Screening Period.
• Current diagnosis of fulminant colitis and/or toxic megacolon.
• Disease limited to the rectum (ulcerative proctitis).
• Current diagnosis of indeterminate colitis.
• Current diagnosis and/or history of Crohns disease (CD).
• Currently receiving total parenteral nutrition.
• Used aminosalicylates for \< 90 days before Baseline or not on a stable dose for at least 28 days before Baseline or discontinued use within 28 days of Baseline.
• Positive Clostridium difficile stool assay.
• Previously used infliximab or any anti-TNF agent within 56 days of Baseline.
• Previously used infliximab or any anti-TNF agent without clinical response at any time ("primary non-responder") unless subject experienced a treatment-limiting reaction.
• Infections requiring treatment with IV antibiotics, antivirals, or antifungals within 30 days of Baseline or oral antibiotics, antivirals, or antifungals within 14 days of Baseline.

Sponsors & Collaborators

• Abbott: lead

Study Sites (108)

Site Ref # / Investigator 5394

Anaheim, California, 92801, United States

Location

Site Ref # / Investigator 3753

Wheat Ridge, Colorado, 80033, United States

Location

Site Ref # / Investigator 3754

Hamden, Connecticut, 06518, United States

Location

Site Ref # / Investigator 12903

Gainesville, Florida, 32607, United States

Location

Site Ref # / Investigator 3747

Hollywood, Florida, 33021, United States

Location

Site Ref # / Investigator 5106

Jacksonville, Florida, 32256, United States

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Site Ref # / Investigator 11601

Naples, Florida, 34102, United States

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Site Ref # / Investigator 6846

Sarasota, Florida, 34239, United States

Location

Site Ref # / Investigator 3742

Winter Park, Florida, 32789, United States

Location

Site Ref # / Investigator 3760

Zephyrhills, Florida, 33542, United States

Location

Site Ref # / Investigator 3739

Atlanta, Georgia, 30342, United States

Location

Site Ref # / Investigator 7658

Macon, Georgia, 31201, United States

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Site Ref # / Investigator 5397

Moline, Illinois, 61265, United States

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Site Ref # / Investigator 7453

Topeka, Kansas, 66606, United States

Location

Site Ref # / Investigator 3759

Annapolis, Maryland, 21401, United States

Location

Site Ref # / Investigator 3762

Annapolis, Maryland, 21401, United States

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Site Ref # / Investigator 3738

Lutherville, Maryland, 21093, United States

Location

Site Ref # / Investigator 7472

Troy, Michigan, 48098, United States

Location

Site Ref # / Investigator 3744

Rochester, Minnesota, 55905, United States

Location

Site Ref # / Investigator 6088

St Louis, Missouri, 63128, United States

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Site Ref # / Investigator 3756

Great Neck, New York, 11021, United States

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Site Ref # / Investigator 3752

Charlotte, North Carolina, 28207, United States

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Site Ref # / Investigator 3758

Jacksonville, North Carolina, 28546, United States

Location

Site Ref # / Investigator 3745

Cincinnati, Ohio, 45219, United States

Location

Site Ref # / Investigator 7709

Oklahoma City, Oklahoma, 73104, United States

Location

Site Ref # / Investigator 3740

Tulsa, Oklahoma, 74104, United States

Location

Site Ref # / Investigator 3765

Sayre, Pennsylvania, 18840, United States

Location

Site Ref # / Investigator 3741

Columbia, South Carolina, 29204, United States

Location

Site Ref # / Investigator 3737

Germantown, Tennessee, 38138, United States

Location

Site Ref # / Investigator 6077

Nashville, Tennessee, 37203, United States

Location

Site Ref # / Investigator 5107

Nashville, Tennessee, 37205, United States

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Site Ref # / Investigator 3743

Nashville, Tennessee, 37212-1610, United States

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Site Ref # / Investigator 5398

Ogden, Utah, 84405, United States

Location

Site Ref # / Investigator 8064

Spokane, Washington, 99202, United States

Location

Site Ref # / Investigator 3750

Spokane, Washington, 99204, United States

Location

Site Ref # / Investigator 3761

West Bend, Wisconsin, 53095, United States

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Site Ref # / Investigator 6853

Buenos Aires, C1181ACH, Argentina

Location

Site Ref # / Investigator 13722

Garran, Australian Capital Territory, 2605, Australia

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Site Ref # / Investigator 16141

Bankstown, New South Wales, NSW 2200, Australia

Location

Site Ref # / Investigator 13723

Herston, Queensland, 4029, Australia

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Site Ref # / Investigator 10706

Bedford Park, South Australia, SA 5042, Australia

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Site Ref # / Investigator 14882

Box Hill, Victoria, 3128, Australia

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Site Ref # / Investigator 9002

Malvern, Victoria, 3144, Australia

Location

Site Ref # / Investigator 10704

Fremantle, Western Australia, 6160, Australia

Location

Site Ref # / Investigator 9802

Vienna, 1090, Austria

Location

Site Ref # / Investigator 5256

Bonheiden, 2820, Belgium

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Site Ref # / Investigator 5253

Brussels, 1070, Belgium

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Site Ref # / Investigator 6225

Brussels, 1200, Belgium

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Site Ref # / Investigator 6079

Ghent, 9000, Belgium

Location

Site Ref # / Investigator 6078

Leuven, 3000, Belgium

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Site Ref # / Investigator 10423

Kelowna, British Columbia, B1Y 1Z9, Canada

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Site Ref # / Investigator 3766

Victoria, British Columbia, V8T 5G4, Canada

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Site Ref # / Investigator 13556

Greater Sudbury, Ontario, P3E 2N8, Canada

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Site Ref # / Investigator 3769

Hamilton, Ontario, L8N 3Z5, Canada

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Site Ref # / Investigator 3736

Toronto, Ontario, M5G 1X5, Canada

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Site Ref # / Investigator 3771

Montreal, Quebec, H3A 1A1, Canada

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Site Ref # / Investigator 3764

Montreal, Quebec, H3G 1A4, Canada

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Site Ref # / Investigator 3768

Montreal, Quebec, H3T 1E2, Canada

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Site Ref # / Investigator 3770

Québec, Quebec, G1S 4L8, Canada

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Site Ref # / Investigator 7021

České Budějovice, 370 87, Czechia

Location

Site Ref # / Investigator 6307

Hradec Kravlove 12, 500 12, Czechia

Location

Site Ref # / Investigator 6606

Olomouc, 775 20, Czechia

Location

Site Ref # / Investigator 7481

Prague, 140 21, Czechia

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Site Ref # / Investigator 7479

Prague, 15006, Czechia

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Site Ref # / Investigator 6483

Hvidovre, DK-2650, Denmark

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Site Ref # / Investigator 7477

Odense C, 5000, Denmark

Location

Site Ref # / Investigator 6231

Clichy, 92110, France

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Site Ref # / Investigator 7476

Lille, 59037, France

Location

Site Ref # / Investigator 7475

Pessac, 33600, France

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Site Ref # / Investigator 7474

Toulouse, 31059, France

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Site Ref # / Investigator 15321

Hamburg, 20148, Germany

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Site Ref # / Investigator 9069

Hamburg, 22559, Germany

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Site Ref # / Investigator 14642

Magdeburg, 39120, Germany

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Site Ref # / Investigator 9067

Minden, 32423, Germany

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Site Ref # / Investigator 14661

Munich, 80639, Germany

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Site Ref # / Investigator 9801

Munich, 81377, Germany

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Site Ref # / Investigator 14761

Münster, 48159, Germany

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Site Ref # / Investigator 5247

Regensburg, 93053, Germany

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Site Ref # / Investigator 7485

Budapest, H-1076, Hungary

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Site Ref # / Investigator 5025

Budapest, H-1135, Hungary

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Site Ref # / Investigator 10625

Debrecen, 4032, Hungary

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Site Ref # / Investigator 14104

Gyula, 5700, Hungary

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Site Ref # / Investigator 4987

Miskoic, H-3051, Hungary

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Site Ref # / Investigator 5036

Miskolc, H-3526, Hungary

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Site Ref # / Investigator 12744

Kfar Saba, 44281, Israel

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Site Ref # / Investigator 10623

Petah Tikva, 49100, Israel

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Site Ref # / Investigator 15361

Tel Aviv, 64239, Israel

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Site Ref # / Investigator 13301

Auckland, 0620, New Zealand

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Site Ref # / Investigator 13181

Auckland, 1148, New Zealand

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Site Ref # / Investigator 13148

Christchurch, 8011, New Zealand

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Site Ref # / Investigator 13482

Hamilton, New Zealand

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Site Ref # / Investigator 9561

Gjøvik, 2819, Norway

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Site Ref # / Investigator 5197

Oslo, 0027, Norway

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Site Ref # / Investigator 6297

Oslo, 0514, Norway

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Site Ref # / Investigator 5194

Tromsø, 9038, Norway

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Site Ref # / Investigator 5193

Trondheim, 7006, Norway

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Site Ref # / Investigator 5242

Lodz, 90-153, Poland

Location

Site Ref # / Investigator 5266

Warsaw, 02 781, Poland

Location

Site Ref # / Investigator 5265

Warsaw, 02-507, Poland

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Site Ref # / Investigator 15263

Wroclaw, 54-144, Poland

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Site Ref # / Investigator 5264

Faro, 8000-386, Portugal

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Site Ref # / Investigator 7473

Lisbon, 1150-314, Portugal

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Site Ref # / Investigator 5263

Lisbon, 1769-001, Portugal

Location

Site Ref # / Investigator 5211

Barcelona, 08036, Spain

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Site Ref # / Investigator 5212

Madrid, 28040, Spain

Location

Site Ref # / Investigator 10221

Basel, 4031, Switzerland

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Site Ref # / Investigator 10222

Bern, 3010, Switzerland

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Site Ref # / Investigator 9162

Zurich, 8091, Switzerland

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

• Wolf D, D'Haens G, Sandborn WJ, Colombel JF, Van Assche G, Robinson AM, Lazar A, Zhou Q, Petersson J, Thakkar RB. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2014 Sep;40(5):486-97. doi: 10.1111/apt.12863. Epub 2014 Jul 15.

  PMID: 25041859 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

• Sandborn WJ, Colombel JF, D'Haens G, Van Assche G, Wolf D, Kron M, Lazar A, Robinson AM, Yang M, Chao JD, Thakkar R. One-year maintenance outcomes among patients with moderately-to-severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2. Aliment Pharmacol Ther. 2013 Jan;37(2):204-13. doi: 10.1111/apt.12145. Epub 2012 Nov 23.

  PMID: 23173821 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 B Thakkar, M.D.

  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: December 5, 2006
• First Posted: December 7, 2006
• Study Start: November 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 3, 2011
• Results First Posted: March 31, 2011

Record last verified: 2011-04

Locations

IL (3); AU (1); CZ (5); ES (2); DK (2); HU (6); US (36); NO (5); AR (1); CA (9); FR (4); NZ (4); CH (3); DE (8); PL (4); PT (3); BE (5)