Long-term effectiveness and Safety of Vedolizumab SC as a Therapy for Ulcerative Colitis and Crohn's Disease

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2015-000482-31-GB
• Date of registration: 08/03/2016
• Prospective Registration: Yes
• Primary sponsor: Takeda Development Centre Europe, Ltd.
• Public title: Long-term effectiveness and Safety of Vedolizumab SC as a Therapy for Ulcerative Colitis and Crohn's Disease
• Scientific title: A Phase 3b Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects with Ulcerative Colitis and Crohn’s Disease - Vedolizumab SC Long-Term Open-Label Extension Study
• Date of first enrolment: 21/03/2016
• Target sample size: 692
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000482-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Colombia, Croatia, Czech Republic, Denmark, Estonia, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Director, Clinical Operations
• Affiliation: Millennium Pharmaceuticals, Inc., wholly owned subsidiary of Takeda Pharmaceutical Company Limited

• Name: Director, Clinical Operations
• Affiliation: Millennium Pharmaceuticals, Inc., wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. The subject has previously participated in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Subjects who withdraw early from Study MLN0002SC-3027 or MLN0002SC-3031 must have withdrawn due to treatment failure (ie, as determined by disease worsening or need for rescue medications from Week 14) during the Maintenance Period.
2. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance.
3. Subjects with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial Screening Visit of MLN0002SC-3027 or MLN0002SC-3031.
4. May be receiving a therapeutic dose of the following drugs provided that the dose has been stable throughout the qualifying double-blind study:
? Oral 5-ASA compounds.
? Oral corticosteroid therapy (prednisone or equivalent steroid at a dose =30 mg/day, budesonide at a dose =9 mg/day).
? Probiotics (eg, Culturelle, Saccharomyces boulardii).
? Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
? Antibiotics used for treatment of IBD (eg, ciprofloxacin, metronidazole).
? Azathioprine or 6-mercaptopurine, provided the subject was receiving this medication during prior participation in Study MLN002SC-3027 or MLN002SC-3031.
? Methotrexate, provided the subject was receiving this medication during prior participation in Study MLN002SC-3031.
5. The subject has previously participated in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Subjects who did not achieve a clinical response at Week 6 and were not randomized into the Maintenance Phase, and achieved a clinical response at Week 14 after receiving a third open-label vedolizumab IV infusion are eligible to participate.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 659
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion criteria:
1. The subject required surgical intervention for UC or CD during or after participation in Study MLN0002SC-3027 or MLN0002SC-3031, currently requires surgical intervention for UC or CD, or is anticipated to require surgical intervention for IBD during this study.
2. The subject has had previous exposure to approved or investigational anti-integrins (eg, natalizumab, efalizumab, etrolizumab, AMG 181) or anti-MAdCAM1 antibodies or rituximab.
3. The subject has had hypersensitivity to any of the vedolizumab excipients.
4. Any live vaccinations within 30 days prior to vedolizumab SC administration.
5. The subject has developed a chronic or severe infection, or, any new, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder during or after participation in a prior vedolizumab study that, in the opinion of the investigator, would confound the study results or compromise subject safety.
6. The subject has withdrawn from Study MLN0002SC-3027 or MLN0002SC-3031due to a study-drug related AE.
7. The subject is unwilling or unable to self inject, or does not have a caregiver (defined as a legal adult) to inject the study medication.
8. The subject has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to enrollment. Subjects with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment.
9. The subject has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or demylinating neurodegenerative disease.
10. The subject has a positive PML subjective symptom checklist prior to the administration of study drug.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Ulcerative Colitis Crohn’s Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: Vedolizumab SC
Product Code: MLN0002 SC
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Vedolizumab SC
CAS Number: 943609-66-3
Current Sponsor code: MLN0002 SC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 108-

Primary Outcome(s)

Primary end point(s): • Subject year adjusted treatment emergent AEs and SAEs during longterm vedolizumab SC treatment.

Main Objective: • To obtain data on long term safety and tolerability on vedolizumab SC in subjects with Ulcerative Colitis (UC) or Crohn's Disease (CD).

Secondary Objective: • To obtain data on adverse events of special interest (AESIs; serious infections including opportunistic infection such as PML, liver injury, malignancies, injection site reactions or systemic reactions and hypersensitivity) in UC and CD subjects receiving long-term vedolizumab SC treatment.
• To obtain data on maintaining clinical response and clinical remission in UC and CD subjects receiving long-term vedolizumab SC treatment.
• To obtain data on patient reported outcomes (PRO) in UC and CD subjects receiving long-term vedolizumab SC treatment.
• To obtain data on work productivity and activity impairment (WPAI-UC; WPAI-CD) in UC and CD subjects receiving long-term vedolizumab SC treatment.
• To obtain data on time to major UC and CD-related events (hospitalizations, bowel surgeries,
and procedures) in UC and CD subjects receiving long-term vedolizumab SC treatment.

Timepoint(s) of evaluation of this end point: Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.

AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.

AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.

Disease activity (Mayo/HBI):
QW and Q2W: Weeks 0, 4, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.

Secondary end point(s): • Subject year adjusted AESIs during long-term vedolizumab SC treatment.
• Proportion of subjects with clinical response during long-term vedolizumab SC treatment using partial Mayo scores defined as a reduction in partial Mayo score of =2 points and =25% from Baseline with an accompanying decrease in rectal bleeding score of =1 or absolute rectal bleeding subscore of =1) in UC subjects and Harvey-Bradshaw Index (HBI) scores (defined as a =3-point decreased in HBI score from baseline) in CD subjects.
• Proportion of subjects with clinical remission during long-term vedolizumab SC treatment using partial Mayo scores (defined as a partial Mayo score of =2 and no individual subscore >1 point) in UC subjects and HBI scores (defined as a HBI score of =4 points) in CD subjects.

Secondary ID(s)

MLN0002SC-3030

2015-000482-31-SK

NCT02620046

Source(s) of Monetary Support

Takeda Development Center Americas, Inc

Ethics review

Status: Approved
Approval date: 21/03/2016
Contact: