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A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis

Phase 3
18 Years
Not Enrolling
Ulcerative Colitis

Thank you

Trial Information

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis

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

The duration of the study was up to 65 weeks, including a Screening Period of up to 3 weeks,
a double-blind (DB) placebo-controlled treatment period of up to 52 weeks, and a 70 day
follow-up phone call for participants who prematurely discontinued or who did not enroll in
the extension study NCT# 00573794 (M10-223).

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 flexible sigmoidoscopy
with biopsy, were to be enrolled at approximately 120 sites worldwide. Planned enrollment
was 500 participants.

Participants were to be stratified by prior exposure to infliximab and/or other anti-TNF
agents, and randomized in a 1:1 ratio to receive ADA or placebo by subcutaneous injection.
Participants assigned to the ADA treatment arm were to receive an induction dose of 160 mg
at Week 0 and 80 mg at Week 2, and 40 mg every other week (eow) starting at Week 4.
Participants assigned to the placebo treatment arm were to receive matching placebo during
the same period of time. At or after Week 10, participants who met the criteria for
inadequate response could be switched to open-label (OL) ADA 40 mg eow beginning at Week 12.
Inadequate response was defined as:

- Partial Mayo score greater than or equal to Baseline score on 2 consecutive visits at
least 14 days apart (for participants with a partial Mayo score of 4 to 7 at Baseline).

- Partial Mayo score greater than or equal to 7 on 2 consecutive visits at least 14 days
apart (for participants with a partial Mayo score of 8 or 9 at Baseline).

Participants who demonstrated inadequate response at 2 consecutive visits at least 14 days
apart while on OL administration ADA 40 mg eow were permitted to dose escalate to ADA 40 mg
weekly (ew). Participants with persistent inadequate response while on ADA 40 mg ew may
have been discontinued from the study at the Investigator's discretion. Upon completion of
the study, participants had the option to enroll into the OL extension Study M10-223 in
which they could receive ADA treatment.

Efficacy and safety measurements were performed throughout the study. A follow-up phone
call was made 70 days after the last dose of study drug to obtain information on any ongoing
or new adverse events (AEs) for all participants who terminated early or who did not enroll
in the OL extension study.

Inclusion Criteria:

1. Participants >=18 years of age and in good health (Investigator discretion) with a
recent stable medical history

2. Diagnosis of UC for greater than 90 days prior to Baseline

3. Diagnosis of active UC 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 >= 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


- 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.

5. 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.

6. Had to be able to self-administer or had caregiver who could reliably administer
subcutaneous (SC) injections.

7. Had to be able and willing to give written informed consent and to comply with the
requirements of the study protocol.

8. 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

- Condoms, sponge, foams, jellies, diaphragm, or intrauterine device

- Oral, parenteral, intravaginal contraceptives for 90 days prior to study drug

- 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.

9. Judged to be in generally good health as determined by the Investigator

Exclusion Criteria:

1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch,
Koch pouch, or ileostomy for UC, or planned bowel surgery.

2. Received previous treatment with ADA or previous participation in an ADA clinical

3. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of

4. Received intravenous (IV) corticosteroids within 14 days of Screening or during the
Screening Period.

5. 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.

6. Current diagnosis of fulminant colitis and/or toxic megacolon.

7. Disease limited to the rectum (ulcerative proctitis).

8. Current diagnosis of indeterminate colitis.

9. Current diagnosis and/or history of Crohns disease (CD).

10. Currently receiving total parenteral nutrition.

11. 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.

12. Positive Clostridium difficile stool assay.

13. Previously used infliximab or any anti-TNF agent within 56 days of Baseline.

14. Previously used infliximab or any anti-TNF agent without clinical response at any
time ("primary non-responder") unless subject experienced a treatment-limiting

15. Infections requiring treatment with IV antibiotics, antivirals, or antifungals within
30 days of Baseline or oral antibiotics, antivirals, or antifungals within 14 days of

16. 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, subject was not to be enrolled in the study.

17. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human
immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system
demyelinating disease, or untreated tuberculosis (TB).

18. Female subject who was pregnant or breast-feeding or considering becoming pregnant
during the study (there should be at least 150 days between the last dose of study
drug and either conception or initiation of breast-feeding in women of childbearing

19. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable
ischemic heart disease, moderate to severe congestive heart failure (CHF), recent
cerebrovascular accident, and any other condition, which in the opinion of the
investigator, put the subject at risk by participation in the protocol.

20. Received any investigational agent within 30 days or 5 half lives prior to Baseline
(whichever was longer).

21. History of clinically significant drug or alcohol abuse during the past year.

22. Known hypersensitivity to the excipients of ADA as stated in the label.

23. Any prior exposure to Tysabri® (natalizumab), or Orencia® (abatacept) or any other
biological therapy [other than Kineret® (anakinra) and anti-TNF agents].

24. Currently taking both budesonide and prednisone (or equivalent) simultaneously.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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).

Outcome Time Frame:

Week 8

Safety Issue:


Principal Investigator

Roopal B Thakkar, M.D.

Investigator Role:

Study Director

Investigator Affiliation:



Canada: Health Canada

Study ID:




Start Date:

November 2006

Completion Date:

March 2010

Related Keywords:

  • Ulcerative Colitis
  • Ulcerative Colitis
  • Adalimumab
  • TNF Antagonist
  • Mayo Score
  • Colitis
  • Colitis, Ulcerative
  • Ulcer



Site Ref # / Investigator 5394Anaheim, California  92801
Site Ref # / Investigator 3753Wheat Ridge, Colorado  80033
Site Ref # / Investigator 3754Hamden, Connecticut  06518
Site Ref # / Investigator 12903Gainesville, Florida  32607
Site Ref # / Investigator 3747Hollywood, Florida  33021
Site Ref # / Investigator 5106Jacksonville, Florida  32256
Site Ref # / Investigator 11601Naples, Florida  34102
Site Ref # / Investigator 6846Sarasota, Florida  34239
Site Ref # / Investigator 3742Winter Park, Florida  32789
Site Ref # / Investigator 3760Zephyrhills, Florida  33542
Site Ref # / Investigator 3739Atlanta, Georgia  30342
Site Ref # / Investigator 7658Macon, Georgia  31201
Site Ref # / Investigator 5397Moline, Illinois  61265
Site Ref # / Investigator 7453Topeka, Kansas  66606
Site Ref # / Investigator 3759Annapolis, Maryland  21401
Site Ref # / Investigator 3762Annapolis, Maryland  21401
Site Ref # / Investigator 3738Lutherville, Maryland  21093
Site Ref # / Investigator 7472Troy, Michigan  48098
Site Ref # / Investigator 3744Rochester, Minnesota  55905
Site Ref # / Investigator 6088St. Louis, Missouri  63128
Site Ref # / Investigator 3756Great Neck, New York  11021
Site Ref # / Investigator 3752Charlotte, North Carolina  28207
Site Ref # / Investigator 3758Jacksonville, North Carolina  28546
Site Ref # / Investigator 3745Cincinnati, Ohio  45219
Site Ref # / Investigator 7709Oklahoma City, Oklahoma  73104
Site Ref # / Investigator 3740Tulsa, Oklahoma  74104
Site Ref # / Investigator 3765Sayre, Pennsylvania  18840
Site Ref # / Investigator 3741Columbia, South Carolina  29204
Site Ref # / Investigator 3737Germantown, Tennessee  38138
Site Ref # / Investigator 3743Nashville, Tennessee  37212-1610
Site Ref # / Investigator 6077Nashville, Tennessee  37203
Site Ref # / Investigator 5107Nashville, Tennessee  37205
Site Ref # / Investigator 5398Ogden, Utah  84405
Site Ref # / Investigator 3750Spokane, Washington  99204
Site Ref # / Investigator 8064Spokane, Washington  99202
Site Ref # / Investigator 3761West Bend, Wisconsin  53095