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

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2005-003482-17-IE
• Date of registration: 10/01/2006
• Prospective Registration: Yes
• Primary sponsor: PDL BioPharma, Inc.
• Public title: A Phase 2, Randomized, Double-blind, Multicenter, Dose-Exploration Study of Visilizumab in Subjects with Intravenous Steroid-Refractory Ulcerative Colitis
• Scientific title: A Phase 2, Randomized, Double-blind, Multicenter, Dose-Exploration Study of Visilizumab in Subjects with Intravenous Steroid-Refractory Ulcerative Colitis
• Date of first enrolment: 03/03/2006
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003482-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Greece, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Eligible subjects will be considered for inclusion in this 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 Modified TrueLove & Witts (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 minimum of 3 consecutive days (i.e. on or after the fourth consecutive day) 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 difficile test within 10 days prior 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.
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 requiring 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; platelet 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 any incidence of medically significant opportunistic infections(*) within the past 12 months. (*) Medically significant opportunistic infections include, but are not limited to, Pneumocystis carinii pneumonia, disseminated CMV, toxoplasmosis, histoplasmosis, progressive multifocal leukoencephalopathy, tuberculosis, aspergillosis, cryptococcal meningitis.

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Intravenous steroid-refractory ulcerative colitis (IVSR-UC)
MedDRA version: 8.0 Level: LLT Classification code 10045265

Intervention(s)

Product Name: Visilizumab (Nuvion)
Product Code: HuM291
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Visilizumab
CAS Number: 219716-33-3
Current Sponsor code: HuM291
Other descriptive name: anti-CD3 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.0-

Primary Outcome(s)

Main Objective: To assess the efficacy, immunogenicity, and safety of three dose levels of visilizumab in subjects with IVSR-UC, and to evaluate optimal dosing.

Primary end point(s): The primary efficacy endpoint is the comparison of the proportion of subjects in each of the three visilizumab dose groups who respond to treatment on Day 45 (± 4 days) in the dose-exploration portion of this study (Stage 1). A subject is defined as a responder if he or she has a = 3-point reduction in the total Mayo score from baseline, with the rectal bleeding subscore reduced by at least 1 point, or an actual rectal bleeding subscore of 0 to 1.

Secondary Objective:

Secondary ID(s)

291-418

Ethics review

Status: Approved
Approval date: 06/04/2004
Contact: