A Phase IIa, Open-Labelled Study of Visilizumab in Patients with Moderate to Severe Inflammatory, Non-Stricturing, Non-Penetrating Forms of Crohn's Disease

ISRCTN ISRCTN16473514
DOI https://doi.org/10.1186/ISRCTN16473514
ClinicalTrials.gov (NCT) NCT00267722
Protocol serial number 291-412
Sponsor PDL BioPharma Inc. (USA)
Funder Protein Design Labs Inc
Submission date
08/09/2005
Registration date
20/02/2006
Last edited
08/02/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

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

abc@email.com

Study information

Primary study designInterventional
Study designTreatment, non-randomized, open label, uncontrolled, single group assignment, efficacy study
Secondary study designRandomised controlled trial
Scientific titleA Phase IIa, Open-Labelled Study of Visilizumab in Patients with Moderate to Severe Inflammatory, Non-Stricturing, Non-Penetrating Forms of Crohn's Disease
Study objectivesTo evaluate the clinical activity of two consecutive daily doses of 10 mcg/kg of visilizumab administered intravenously to patients with moderate to severe inflammatory, non-stricturing, non-penetrating forms of Crohn's disease
Ethics approval(s)Approved by the Medical Ethics Committee on 03/02/2005, (ref: 04/325)
Health condition(s) or problem(s) studiedCrohn's disease
InterventionTwo consecutive daily doses of 10 mcg/kg of visilizumab administered intravenously. Taking of blood samples, endoscopy and biopsies.
Intervention typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Visilizumab
Primary outcome measure(s)

To evaluate the clinical activity of two consecutive daily doses of 10 mcg/kg of visilizumab administered intravenously to patients with moderate to severe inflammatory, non-stricturing, non-penetrating forms of Crohn's disease

Key secondary outcome measure(s)

1. To evaluate the pharmacokinetics of two consecutive daily doses of 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 visilizumab in this patient population
4. To evaluate the safety, tolerability, clinical activity, pharmacokinetics and immunogenicity of retreatment (if warranted) of two consecutive daily doses of 10 mcg/kg visilizumab in patients with moderate-to-severe inflammatory, non-stricturing, non-penetrating forms of Crohn's disease

Completion date31/08/2007

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration20
Key inclusion criteria1. Male or female, 18 to 70 years of age
2. A diagnosis of moderate-to-severe inflammatory, non-stricturing, non-penetrating Crohn’s disease, defined as Crohn’s Disease Activity Index (CDAI) >/= 250, C-Reactive Protein (CRP) >/= Upper Limit of Normal (ULN) and endoscopic evidence of moderate-to-severe active inflammatory disease
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 negative serum pregnancy test
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 authorization to use protected health information (US sites only)
7. Patients who have Epstein-Barr virus (EBV) Deoxyribonucleic Acid (DNA) titers up to 30,000 copies/ml
Key exclusion criteria1. 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 has been adequately treated)
2. Pregnant women or nursing mothers
3. Any of the following hematologic abnormalities: White Blood Cell (WBC) <2500 /mm^3, platelets <150,000 /mm^3, hemoglobin <10 g/dl
4. Serologic evidence of infection with Human Immunodeficiency Virus (HIV) or Hepatitis B or C virus (HBV, 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 the study drug
6. Serious infections, particularly those of viral etiology e.g. known active cytomegalovirus (CMV) colitis, and patients who have had a history of opportunistic infections within the past year
7. Active infections that require antibiotic therapy (not to include use of antibiotics to control Crohn’s disease)
8. Started, or have a dose change of, sulfasalazine, 5-aminosalicylic acid (5-ASA), or antibiotics, probiotics, or topical therapies for Crohn’s disease within two weeks prior to receiving the study drug
9. Serious infections that required intravenous (IV) antibiotic therapy or hospitalization within eight weeks prior to receiving the study drug
10. Had an increased dose in corticosteroid medication two weeks prior to receiving the study drug, is receiving IV steroids, or, is receiving a daily dose of >40 mg prednisone, >9 mg budesonide, or equivalent
11. Received a live vaccine within six weeks prior to receiving the study drug (patients may not receive a live vaccine during treatment or for 12 weeks after treatment with the study drug)
12. Received any monoclonal antibodies (including infliximab) or investigational agents or biologics within three months prior to receiving the study drug
13. Received cyclosporine or tacrolimus (FK506) within four weeks of receiving the study drug
14. Had a dose change of, or discontinued from, 6-mercaptopurine, azathioprine, or methotrexate within four weeks prior to receiving the study drug
15. Significant organ dysfunction, including cardiac, renal, liver, Central Nervous System (CNS), pulmonary, vascular, non-Crohn's disease-related gastrointestinal, endocrine, or metabolic (e.g. creatinine >1.6 mg/dl, alanineamino transferase [ALT] or aminotransferase [AST] > twice the Upper Limit of Normal [ULN], alkaline phosphatase >1.5 x ULN, history of myocardial infarction, congestive heart failure, or arrhythmias within six months prior to receiving the study drug)
16. Likely to require surgery in the next six months, such as those with clinically apparent abscesses or severely symptomatic stenoses
17. History of lymphoproliferative 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 Crohn’s disease (not including joint, skin, hepatic, and ocular inflammatory conditions that may be more typically associated with Crohn’s disease)
21. History of seizure with subtherapeutic blood levels of anticonvulsive medication (documented) within one week before study enrolment
Date of first enrolment01/10/2004
Date of final enrolment31/08/2007

Locations

Countries of recruitment

  • Germany
  • Netherlands
  • United States of America

Study participating centre

Academic Medical Center
Amsterdam
1105AZ
Netherlands

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article cytokine release syndrome results 01/04/2009 08/02/2019 Yes No

Editorial Notes

08/02/2019: Publication reference added.

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