Contact information
Type
Scientific
Primary contact
Dr Daniel Hommes
ORCID ID
Contact details
Academic Medical Center
Department of Gastroenterology
Room C2-330
Melbergdreef 9
Amsterdam
1105AZ
Netherlands
d.w.hommes@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
291-408
Study information
Scientific title
Acronym
Study hypothesis
To evaluate the safety and tolerability of visilizumab when administered to patients with severe ulcerative colitis (UC) that is refractory to intravenous steroids.
Ethics approval
Ethics approval received from the local Medical Ethics Committee on 15th October 2003 (ref: 03/220).
Study design
Partially randomised, open labelled study, phase I/II
Primary study design
Interventional
Secondary study design
Multi-centre
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Condition
Ulcerative colitis
Intervention
In stage 1, patients were randomised to receive one of the following doses: 5.0 or 7.5 or 10.0 or 12.5 µg/kg. Due to amendment C (dated 06/05/2005) it was decided that in stage 2 all patients would receive 5.0 µg/kg. Visilizumab was administered intravenously on two consecutive daily doses.
Intervention type
Drug
Phase
Phase I/II
Drug names
Visilizumab
Primary outcome measures
To evaluate the safety of tolerability of visilizumab when administered to patients with severe UC that is refractory to IV steroids.
Secondary outcome measures
1. To obtain preliminary evidence of biological activity in this indication. This will be assessed by quantifying the number of patients who experience an improvement in disease symptoms (as indicated by a decrease in scores on Modified Truelove and Witts Severity Index [MTWSI] and a Mayo-Clinic system for assessing UC activities), and to avoid surgical intervention
2. To compare patients with and without detectable whole blood Epstein-Barr Virus (EBV) for the safety profiles of visilizumab
3. To determine the optimal clinical dose (OCD) of visilizumab in the study patient population
4. To determine relationships between pharmacokinetics and pharmacodynamics of visilizumab, laboratory immunologic parameters, clinical response and toxicity
5. To evaluate the safety and tolerability of a second course of treatment with visilizumab when administered to patients who responded to a first course, but subsequently relapsed
Overall trial start date
01/07/2003
Overall trial end date
31/01/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. 18 to 70 years of age
2. A diagnosis of UC verified by colonoscopy or barium enema performed within 36 months prior to study entry
3. For first time therapy with visilizumab, active disease documented by a Modified Truelove and Witts Severity Index (MTWSI) score of 11 to 21 despite a course of intravenous (IV) steroids that occurred within 60 days prior to study day one and lasted at least five days. Patients who undergo re-treatment with visilizumab must meet the same MTWSI score requirement but need not to have failed IV steroids before re-treatment
4. If patient is a male or female of reproductive potential, he or she must agree to use adequate contraception during the study and for three months after receiving visilizumab
5. For women of childbearing potential, a negative serum pregnancy test at baseline screening
6. Patients must have been tested negative for Clostridium difficile within 10 days prior to treatment with visilizumab
7. Patients who are capable of understanding the purpose and risks of the study and who provide a signed and dated informed consent. For US sites only, patients must also provide an authorisation to use protected health information.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
144
Participant exclusion criteria
1. Ulcerative colitis (UC) requiring immediate surgical, endoscopic, or radiologic interventions, including massive haemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or perianal abscesses) or toxic megacolon
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 10^3/µl, platelet count less than 150 x 10^3µl, or haemoglobin less than 8 g/dl
5. Patients with serious infections, particularly those of viral etiology, e.g. active cytomegalovirus (CMV) colitis. This includes any incidence of opportunistic infections within the past year.
6. Patients who have received a live vaccine within six weeks prior to study entry (patients may not receive a live vaccine during treatment or for six weeks after treatment with visilizumab)
7. Patients with a history of thrombophlebitis or pulmonary embolus
8. Significant organ dysfunction including: cardiac, renal, liver, central nervous system, pulmonary, vascular, gastrointestinal endocrine or metabolic dysfunction (e.g. creatinine greater than 1.6 mg/dl, or alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase greater than 1.5 x upper limit of normal) or history of coronary artery disease within six months prior to study entry
9. Patients with a history of lymphoproliferative disorder (LPD) or malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix that has been adequately treated
10. Pregnant women or nursing mothers
11. Seropositive for infection with human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HBC) antibody
12. An Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) load greater than 5000 copies/ml in stage 1 and greater than 30,000 copies/ml in stage 2
13. Treatment with any investigational drugs or therapies within 60 days prior to study entry
14. Treatment with an antibody therapy within 60 days prior to study entry
15. Treatment with cyclosporine or tacrolimus (FK506) within three months prior to study entry
16. All of the following: a history of seizures, a history of both chronic and current treatment with anticonvulsant medication, and no documentation of therapeutic blood levels of anticonvulsant medication within seven days before study enrolment
Recruitment start date
01/07/2003
Recruitment end date
31/01/2006
Locations
Countries of recruitment
Austria, Belgium, Bulgaria, Canada, Germany, Netherlands, United States of America
Trial participating centre
Academic Medical Center
Amsterdam
1105AZ
Netherlands
Sponsor information
Organisation
PDL BioPharma Inc. (USA)
Sponsor details
34801 Campus Drive
Fremont
94587
United States of America
mdyer@pdl.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
PDL BioPharma Inc. (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary