A Study of Abatacept in Patients With Active Ulcerative Colitis

NCT00410410 | Completed Phase 3 Results DMC

• 1 other identifier: IM101-108
• Study Type: interventional
• Target: 591
• Locations: 19 countries
• Sites: 143

Brief Summary

The purpose of this clinical research study is to learn if abatacept can improve signs and symptoms of active ulcerative colitis in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (8)

• Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)

  The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.

  Week 12 (Day IP-85)

• Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12

  The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.

  Month 12 (Day MP-365)

• Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  Day OL-1 through the end of the OL

• OL; Number of Participants With AEs of Special Interest

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).

  Day OL-1 through Day OL-729

• OL; Number of Participants With Physical Examination Findings

  Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).

  Day OL-1 through Day OL-729

• OL; Number of Participants With Marked Hematology Laboratory Abnormalities

  High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Erythrocytes: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL/ \>7.50 x 10\^3 c/uL.

  Day OL-1 through Day OL-729

• OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities

  Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): \>2 x ULN; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; potassium (K): \<0.9 x LLN/ \>1.1 x ULN; calcium (Ca): \<0.8 x LLN/\>1.2 x ULN; phosphorous (P): \<0.75 x LLN/ \>1.2 5 x ULN

  Day OL-1 through Day OL-729

• OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities

  Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): \<65 mg/dL/ \>220 mg/dL; fasting serum Glu: \<0.8 x LLN/ \>1.5 x ULN; total protein: \< 0.9 x LLN/ \>1.1 x ULN; albumin:\<0.9 x LLN; uric acid: \>1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells \[RBCs\], White Blood Cells \[WBCs\]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3

  Day OL-1 through Day OL-729

Secondary Outcomes (47)

• IP; Baseline Mayo Score: IP1C

  Baseline

• IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C

  Week 12 (Day IP-85)

• IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C

  Week 12 (Day IP-85)

• IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C

  Week 12 (Day IP-85)

• IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C

  Baseline

Study Arms (3)

Abatacept (ABA)

EXPERIMENTAL

Induction Period; 3 arms for Cohort 1: ABA 30/\~10 mg/kg (ABA administered at 30 mg/kg followed by ABA at \~10 mg/kg), ABA \~10 mg/kg, ABA 3 mg/kg Induction Period; 2 arms for Cohort 2: ABA 30/\~10 mg/kg and Second Cohort ABA \~10 mg/kg 1 arm for maintenance period (ABA \~10 mg/kg)

Drug: abatacept (ABA)

Placebo

PLACEBO COMPARATOR

1 arm for induction period 1 arm for maintenance period

Drug: placebo

abatacept

OTHER

1 arm for open-label extension phase (ABA \~10 mg/kg)

Drug: abatacept

Interventions

abatacept (ABA) DRUG

Dextrose 5% in water, IV. Placebo on days IP-1, IP-15,IP-29, IP-57; 3 mg/kg on days IP-1, IP-15,IP-29, IP-57; 10 mg/kg on days IP-1, IP-15,IP-29, IP-57; or 30 mg/kg on days IP-1,IP-15 and \~10 mg/kg on days IP-29, IP-57 (ABA 30/\~10 mg/kg Group). Induction Period 3 months Maintenance Period 12 months

Also known as: Orencia, BMS-188667

Abatacept (ABA)

placebo DRUG

Normal saline, IV, 0 mg/kg, every 28 days. Induction Period 3 months Maintenance Period 12 months

Placebo

abatacept DRUG

\~10 mg/kg, once monthly Open- Label Extension Period until the drug is marketed for UC or the UC development program for abatacept is discontinued

Also known as: Orencia, BMS-188667

abatacept

Eligibility Criteria

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

You may qualify if:

• Men or women 18 years or older
• Ulcerative colitis for at lease 3 months
• Moderate to severe active ulcerative colitis
• Inadequate response or intolerance to standard ulcerative colitis treatment

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (143)

University Of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

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The Permanente Medical Group, Inc

Sacramento, California, 95825, United States

Location

Western States Clinical Research Inc.

Wheat Ridge, Colorado, 80033, United States

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Litchfield County Gastroenterology Assoc.

Torrington, Connecticut, 06790, United States

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University Of Florida

Gainesville, Florida, 32610, United States

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Borland-Groover Clinic

Jacksonville, Florida, 32256, United States

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Miami Research Associates

Miami, Florida, 33143, United States

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Shafran Gasteroenterology Center

Winter Park, Florida, 32789, United States

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Atlanta Gastroenterology Associates

Atlanta, Georgia, 30342, United States

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Rush University Medical Center

Chicago, Illinois, 60612, United States

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University Of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

Health Science Center

Pratt, Kansas, 67124, United States

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University Of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

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University Of Louisville

Louisville, Kentucky, 40202, United States

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Gulf Coast Research

Lafayette, Louisiana, 70503, United States

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Clinical Pharmacology Study Group

Worcester, Massachusetts, 01610, United States

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Minnesota Gastroenterology, P.A.

Plymouth, Minnesota, 55446, United States

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Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

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Kansas City Gastroenterology And Hepatology

Kansas City, Missouri, 64131, United States

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Center For Digestive & Liver Diseases, Inc.

Mexico, Missouri, 65265, United States

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Aga Clinical Research Associates, Llc

Egg Harbor Twp, New Jersey, 08234, United States

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Hudson Valley Medical Research Llc

Fishkill, New York, 12524, United States

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Long Island Clinical Research

Great Neck, New York, 11021, United States

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Mount Sinai School Of Medicine

New York, New York, 10029, United States

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University Of Rochester Medical Center

Rochester, New York, 14642, United States

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Good, Larry I.

Rockville Centre, New York, 11570, United States

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Gastrointestinal Resrch Assoc.

Setauket, New York, 11733, United States

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University Of North Carolina

Chapel Hill, North Carolina, 27599, United States

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Charlotte Gastroenterology & Hepatology, Pllc

Charlotte, North Carolina, 28207, United States

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Hanover Medical Specialists, P.A.

Wilmington, North Carolina, 28401, United States

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Piedmont Medical Research Associates

Winston-Salem, North Carolina, 27103, United States

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Gastroenterology Specialists, Inc.

Canton, Ohio, 44718, United States

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Consultants For Clinical Research, Inc.

Cincinnati, Ohio, 45219, United States

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Gastrointestinal & Liver Diseases Consultants

Dayton, Ohio, 45415, United States

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Oklahoma Foundation For Digestive Research

Oklahoma City, Oklahoma, 73104, United States

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Options Health Research, Llc

Tulsa, Oklahoma, 74104, United States

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Healthcare Research Consultants

Tulsa, Oklahoma, 74135, United States

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Hospital Of The University Of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

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Allegheny Center For Digestive Health

Pittsburgh, Pennsylvania, 15212, United States

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Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

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Gastroenterology Center Of The Midsouth, P.C.

Germantown, Tennessee, 38138, United States

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Memphis Gastroenterology Group

Germantown, Tennessee, 38138, United States

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Nashville Medical Research

Nashville, Tennessee, 37205, United States

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Austin Gastroenterology, Pa

Austin, Texas, 78705, United States

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Alamo Medical Research

San Antonio, Texas, 78215, United States

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Gastroenterology Clinic Of San Antonio

San Antonio, Texas, 78229, United States

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Virginia Mason Medical Center

Seattle, Washington, 98101, United States

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Tacoma Digestive Disease Research Ctr.

Tacoma, Washington, 98405, United States

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Local Institution

Garran, Australian Capital Territory, 2605, Australia

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Camperdown, New South Wales, 2050, Australia

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Herston, Queensland, 4029, Australia

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South Brisbane, Queensland, 4101, Australia

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Bedford Park, South Australia, 5042, Australia

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Launceston, Tasmania, 7250, Australia

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Box Hill, Victoria, 3128, Australia

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Fitzroy, Victoria, 3065 VIC, Australia

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South Ballarat, Victoria, 3350, Australia

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Fremantle, Western Australia, 6160, Australia

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Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Salvador, Estado de Bahia, 42700, Brazil

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Goiânia, Goiás, 74535, Brazil

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Curitiba, Paraná, 80060, Brazil

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Rio de Janeiro, Rio de Janeiro, 21941, Brazil

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Porto Alegre, Rio Grande do Sul, 90035, Brazil

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Porto Alegre, Rio Grande do Sul, 90610, Brazil

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Campinas, São Paulo, 13070, Brazil

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Santo Andre - Sp, São Paulo, 09060, Brazil

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Santos, São Paulo, 11075, Brazil

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São Paulo, São Paulo, 01246, Brazil

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Vancouver, British Columbia, V5Z 1H2, Canada

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Vancouver, British Columbia, V6Z 2K5, Canada

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Kingston, Ontario, K7L 5G2, Canada

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London, Ontario, N6A 5A5, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M3N 2V7, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Lévis, Quebec, G6V 3Z1, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Québec, Quebec, G1L 3L5, Canada

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Brno-Bohunice, 625 00, Czechia

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České Budějovice, 370 87, Czechia

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Amiens, 80054, France

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Clichy, 92110, France

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Lille, 59037, France

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Nice, 06200, France

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Paris, 75475, France

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Pessac, 33604, France

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Toulouse, 31059, France

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Kiel, 24105, Germany

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Münster, 48129, Germany

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Münster, 48159, Germany

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Hyderabad, Andhra Pradesh, 500082, India

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Kochi, Kerala, 682304, India

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Mumbai, Maharashtra, 400020, India

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Bangalore, 560017, India

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Bangalore, 560034, India

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Delhi, 110076, India

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Hyderabad, 500058, India

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Mangalore, 575001, India

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Manipal, 576104, India

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Mumbai, 400 022, India

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Mumbai, 400 029, India

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Mysore, 570004, India

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Dublin, Dublin, Ireland

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Napoli, 80138, Italy

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Padua, 35128, Italy

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Roma, 00133, Italy

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Roma, 00152, Italy

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San Giovanni Rotondo, 71013, Italy

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Chihuahua City, Chihuahua, 31238, Mexico

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Torreón, Coahuila, 27250, Mexico

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Guadalajara, Jalisco, 44160, Mexico

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Guadalajara, Jalisco, 44200, Mexico

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Guadalajara, Jalisco, 44340, Mexico

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Guadalajara, Jalisco, 45050, Mexico

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Guadalajara, Jalisco, 45200, Mexico

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Df, Mexico City, 11560, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Mexico, D. F., Mexico City, 06726, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Culiacán, Sinaloa, 80230, Mexico

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Hermosillo, Sonora, 83280, Mexico

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Amersfoort, 3816 CP, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Groningen, 9700 RB, Netherlands

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Katowice, 40-752, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 50-326, Poland

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Ponce, 00716, Puerto Rico

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Parktown West, Gauteng, 2193, South Africa

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Pretoria, Gauteng, 0048, South Africa

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Overport, KwaZulu-Natal, 4091, South Africa

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Belville, Western Cape, 7350, South Africa

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Panorama, Western Cape, 7506, South Africa

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Seoul, 120-752, South Korea

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Bern, 3010, Switzerland

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Zurich, 8091, Switzerland

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London, Greater London, E1 1BB, United Kingdom

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London, Greater London, WC1E 6DB, United Kingdom

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Oxford, Oxfordshire, OX 39DU, United Kingdom

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Related Publications (1)

• Sandborn WJ, Colombel JF, Sands BE, Rutgeerts P, Targan SR, Panaccione R, Bressler B, Geboes K, Schreiber S, Aranda R, Gujrathi S, Luo A, Peng Y, Salter-Cid L, Hanauer SB. Abatacept for Crohn's disease and ulcerative colitis. Gastroenterology. 2012 Jul;143(1):62-69.e4. doi: 10.1053/j.gastro.2012.04.010. Epub 2012 Apr 12.

  PMID: 22504093 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Abatacept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Limitations and Caveats

This study was terminated after review of the IP1C results due to lack of efficacy. Enrollment for the MP and for IP2C was not completed. Participants in MP, IP2C, and OL were early terminated at the time of study termination.

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 12, 2006
• Study Start: December 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: November 1, 2009
• Last Updated: March 24, 2015
• Results First Posted: December 2, 2010

Record last verified: 2015-03

Locations

IE (1); US (50); ZA (5); PL (3); DE (3); CH (2); ME (13); AU (10); NL (3); IT (5); BE (2); PR (1); CZ (2); CA (10); GB (3); BR (10); FR (7); IN (12); KR (1)