A phase I/II, partially randomised, open-labelled study of visilizumab in patients with severe ulcerative colitis refractory to intravenous corticosteroids

ISRCTN	ISRCTN94152325
DOI	https://doi.org/10.1186/ISRCTN94152325
Secondary identifying numbers	291-408

Submission date: 08/09/2005
Registration date: 20/02/2006
Last edited: 09/09/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Daniel Hommes
Scientific

Academic Medical Center
Department of Gastroenterology
Room C2-330
Melbergdreef 9
Amsterdam
1105AZ
Netherlands

Email	d.w.hommes@amc.uva.nl

Study information

Study design	Partially randomised, open labelled study, phase I/II
Primary study design	Interventional
Secondary study design	Multi-centre
Study setting(s)	GP practice
Study type	Treatment
Scientific title
Study objectives	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(s)	Ethics approval received from the local Medical Ethics Committee on 15th October 2003 (ref: 03/220).
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Visilizumab
Primary outcome measure	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 study start date	01/07/2003
Completion date	31/01/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	144
Key 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.
Key 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
Date of first enrolment	01/07/2003
Date of final enrolment	31/01/2006

Locations

Countries of recruitment

Austria
Belgium
Bulgaria
Canada
Germany
Netherlands
United States of America

Study participating centre

Academic Medical Center

Amsterdam
1105AZ
Netherlands

Sponsor information

PDL BioPharma Inc. (USA)
Industry

34801 Campus Drive
Fremont
94587
United States of America

Email	mdyer@pdl.com
Website	http://www.pdl.com/
"ROR"	https://ror.org/03ya6pd97

Funders

Funder type

Industry

PDL BioPharma Inc. (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan