A phase IIa, open label study of visilizumab for the treatment of perianal fistulas in patients with Crohn's disease

ISRCTN	ISRCTN65243779
DOI	https://doi.org/10.1186/ISRCTN65243779
ClinicalTrials.gov number	NCT00267709
Secondary identifying numbers	291-411

Submission date: 08/09/2005
Registration date: 20/02/2006
Last edited: 31/01/2019

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

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	Treatment, non-randomised, open labelled, uncontrolled, single group assignment, efficacy study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Screening
Scientific title	A phase IIa, open label study of visilizumab for the treatment of perianal fistulas in patients with Crohn's disease
Study hypothesis	To evaluate the clinical activity of two consecutive daily doses of 10 µg/kg visilizumab administered intravenously to patients with draining perianal fistulas associated with Crohn's disease
Ethics approval(s)	Ethics approval received from the Medical Ethics Committee on the 3rd February 2005 (ref: 04/318)
Condition	Crohn's disease
Intervention	Two consecutive daily doses of 10 µg/kg of visilizumab administered intravenously. 1. Taking of blood samples 2. Flexible sigmoidoscopy and biopsy 3. Magnetic resonance imaging (MRI) of fistulas
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Visilizumab
Primary outcome measure	To evaluate the clinical activity of two consecutive daily doses of 10 µg/kg visilizumab administered intravenously to patients with draining perianal fistulas associated with Crohn's disease
Secondary outcome measures	1. To evaluate the pharmacokinetics of two consecutive doses of 10 µg/kg visilizumab administered intravenously in this patient population 2. To determine the risk-benefit relationship of visilizumab in this patient population 3. To assess immunogenicity of visulizumab in this patient population 4. To evaluate the safety, clinical activity, pharmacokinetics and immunogenicity of retreatment (if warranted) of two consecutive daily doses of 10 µg/kg visilizumab in patients with perianal fistulas associated with Crohn's disease
Overall study start date	01/10/2004
Overall study end date	31/08/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	20
Total final enrolment	20
Participant inclusion criteria	1. Male or female, 18 to 70 years of age 2. A diagnosis of Crohns disease and at least one documented external, draining, perianal fistula 3. Patients with reproductive potential who agree to use double-barrier methods of contraception during the study and for three months after receiving the study drug 4. Women of childbearing potential who have a negative serum pregnancy test at baseline screening 5. Patients who have been tested negative for Clostridium difficile within three weeks prior to treatment with the study drug 6. Patients who are capable of understanding the purpose and risks of the study and who provide signed and dated informed consent and an authorisation to use protected health information (US sites only) 7. Patients who have Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) titres up to 30,000 copies/ml
Participant exclusion criteria	1. History of lymphoproliferative disorder or a prior malignancy within five years or current malignancies (excluding non-melanoma skin cancers or in situ carcinoma of the cervix that had been adequately treated) 2. Pregnant women or nursing mothers 3. Any of the following haematological abnormalities: white blood cells (WBC) less than 2500/mm^3, platelets less than 150,000/mm^3, haemoglobin less than 10 g/dl 4. Serologic evidence of infection with human immunodeficiency virus (HIV) or hepatitis B or C virus (HBV or HCV) 5. Presence of obstructive symptoms, confirmed by endoscopy showing an impassable stricture or computed tomography (CT) or barium studies showing stricture with prestenotic bowel dilation, within six months prior to receiving study drug 6. Likely to require surgery in the next six months, such as those with clinically apparent abscesses or severely symptomatic stenoses (patients with fistula abscesses and/or setons at screening may be eligible for study entry if abscesses can be drained before patients receive study drug) 7. Serious infections, particularly those of viral etiology, e.g. known as active cytomegalovirus (CMV) colitis, and who have a history of opportunistic infections with the past year 8. Active infections that require antibiotic therapy (not to include use of antibiotics to manage Crohns disease) 9. Serious infections that require intravenous (IV) antibiotic therapy or hospitalisation within eight weeks prior to receiving study drug 10. Started, or have had a change of sulfasalazine; 5-aminosalicylic acid (5-ASA) or antibiotics, probiotics, or topical therapies for Crohns disease within two weeks prior to receiving the study drug 11. Had an increased dose of corticosteroid medication within two weeks prior to receiving the study drug, is receiving intravenous (IV) steroids, or, is receiving a daily dose of greater than 40 mg prednisone, greater than 9 mg budesonide or equivalent 12. Received a live vaccine within six weeks prior to receiving study drug (patients may not receive a live vaccine during treatment or for 12 weeks after treatment with the study drug) 13. Received any monoclonal antibodies (including infliximab) or investigational agents or biologics within three months prior to receiving the study drug 14. Received cyclosporine or tacrolimus (FK506) within four weeks of receiving the study drug 15. Had a dose change of, or discontinued from, 6-mercaptopurine, azathioprine or methatrexate within four weeks prior to receiving the study drug 16. Significant organ dysfunction, including cardiac, renal, liver, central nervous system (CNS), pulmonary, vascular, non-Crohns disease related gastrointestinal, endocrine or metabolic (e.g. creatinine greater than 1.6 mg/dl, alanine aminotranferease [ALT] and aspartate aminotransferase [AST] greater than twice the upper limit of normal [ULN], alkaline phosphatase greater than 1.5 x ULN, history of myocardial infarction, congestive heart failure or arrhythmias within six months prior to study entry) 17. History of proliferative disorder 18. History of tuberculosis (TB) or other mycobacterial infection, or chest X-ray positive for previous TB infection 19. History of thrombophlebitis or pulmonary embolus 20. Histories of immune deficiency or autoimmune disorders other than Crohns disease (not including joint, skin, hepatic, and occular inflammatory conditions that may be components of Crohns disease) 21. History of seizure with subtherapeutic blood levels of anticonvulsive medication (documented) within one week before study enrolment
Recruitment start date	01/10/2004
Recruitment end date	31/08/2007

Locations

Countries of recruitment

Austria
Belgium
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

Editorial Notes

31/01/2019: No publications found, verifying results status with the principal investigator