A Phase 2, Randomized, Double-blind, Multicenter, Dose-exploration Study of Visilizumab in Subjects with Intravenous Steroid-Refractory Ulcerative Colitis

• Conditions: Intravenous steroid-refractory ulcerative colitis (IVSR-UC); MedDRA version: 9.0Level: LLTClassification code 10045365

• Registration Number: EUCTR2005-003482-17-GB
• Lead Sponsor: PDL BioPharma, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

Eligible subjects will be considered for inclusion in theis study if they meet all of the following criteria:

1) Males & females, 18 years of age or older.

2) Diagnosis of UC, as verified by colonoscopy or barium enema performed within 36 months prior to consent.

3) Severe active disease, as defined by MTWSI =11 at consent, with a confirmatory MTWSI =10 on or after the fifth consecutive day of IV steroids and within 1 day prior to randomization/registration.

4) Mayo score =10 and a Mayo mucosal subscore (finding of flexible proctosigmoidoscopy) of =2. The Mayo score will be calculated on the day of sigmoidoscopy by a blinded gastroenterologist, after a minium of 3 consecutive days (i.e. on or after the fourth consecutive days) of IV steroids.

5) Agreement to use adequate contraception by male or female subjects of reproductive potential throughout the study and for 3 months after receiving the last dose of study drug.

6) Negative serum pregnancy test at screening in female subjects of childbearing potential.

7) Negative clostridium diffiile test within 10 days prioir to the first dose of study drug.

8) Ability to understand the purpose and risks of the study and provide signed and dated informed consent. For US sites only, subjects must also provide an authorization to use protected health information (in accordance with the health Insurance Portability and Accountability Act or HIPAA in the US).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects will be ineligible for this study if they meet any one of the following criteria:

1) UC requiring immediate surgical, endoscopic, or radiologic interventions, including massive hemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or perianal abscesses), or toxic megacolon reequiring imminent intervention.

2) History of total proctocolectomy, or subtotal colectomy with ileorectal anastomosis.

3) Presence of ileostomy.

4) White blood cell count less than 2.5 x 10 (E3)/mcL; platlet count less than 150 x 10 (E3)/mcL; or hemoglobin level less than 8g/dL.

5) Active medically significant infections, particularly those of viral etiology, e.g. known CMV colitis. This includes and incidence of medically significant opportunistic infections(*) within the past 12 months.
(*) As stated in Definitionson page 10 of the Study Protocol: These include but are not limited to Pneumocystisis carinii pneumonia, disseminated CMV, toxoplasmosis, histoplasmosis, herpes simplex of the skin, candidiasisi of the mouth etc.

6) Live vaccination within 6 weeks prior to randomization (SuBjects may not receive a live vaccine during dosing or for 60 days after receiving the last dose of study drug).

7) History of deep vein thrombophlebitis or pulmonary embolus.

8) Significant organ dysfunction, inluding cardiac, renal, liver, CNS, pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality (e.g. creatinine =1.6 mg/dL; ALT or AST = 1.5X the upper limit of normal [ULN]; alkaline phosphatase = 1.5X ULN); a history of myocardial infarction, coronary artery disease, congestive heart failure, or arrhythmias within 6 months prior to consent.

9) History of lymphoproliferative disorder (LPD) or malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix that has been adequately treated.

10) Seropositive for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV) antibody.

11) Infliximab-treated subjects may not receive study drug until 4 weeks after their first dose or 2 weeks after a subsequent dose of infliximab.

12) Treatment with cyclosporine or tacrolimus (FK506) within 2 weeks prior to randomization.

13) Treatment with any other investigational drug or therapy within 60 days prior to randomization.

14) Any condition that, in the investigator’s opinion, makes the subject unsuitable for study participation.

15) Initiation or increase of dosing of 6-mercaptopurine, azathioprine, or methotrexate within 60 days immediately prior to randomization.

16) Failure to discontinue any UC drug (including, but not limited to 6-mercaptopurine, azathioprine, or methotrexate), except glucocorticoids or 5-ASA, prior to randomization.

17) Pregnancy or nursing.

18) Nontherapeutic levels of chronic anti-seizure medications in subjects with a prior history of seizures, as tested within 4 days prior to randomization.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified