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A Study of Vedolizumab in People With Ulcerative Colitis and Crohn's Disease

Phase 4
Completed
Conditions
Ulcerative Colitis
Crohn Disease
Interventions
Registration Number
NCT04804540
Lead Sponsor
Takeda
Brief Summary

Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, people with ulcerative colitis or Crohn's disease will be treated with vedolizumab. The main aim of the study is to check for side effects from vedolizumab.

At the first visit, the study doctor will check who can take part. Participants will receive vedolizumab slowly through a vein (infusion). Participants will regularly visit the clinic for up to 46 weeks for more infusions of Vedolizumab. During these visits, the study doctor will check if there are any side effects from this treatment.

Participants will visit the clinic for a final check-up up to 16 weeks after their final infusion of Vedolizumab. Clinic staff will arrange a phone call 6 months after their final infusion of Vedolizumab for a further check-up.

Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have active UC or CD.

The study will enroll approximately 150 patients. Participants will be assigned to the vedolizumab treatment group.

•Vedolizumab 300 mg

Vedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2, 6 and 10 (CD-participants who have not shown a response can receive a dose at Week 10) during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase.

This multicentre trial will be conducted in India. The overall time to participate in this study is 74 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone plus a final visit after receiving their last dose of drug for a follow-up assessment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
Inclusion Criteria
  1. Has a diagnosis of moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) at least 3 months prior to screening, with a Full Mayo Score of 6-12 for UC and a Harvey Bradshaw Index (HBI) score of >=8 for CD at the time of enrolment.

  2. Has demonstrated, an inadequate response to, loss of response to, or intolerance to at least 1 of the following agents:

    1. Conventional therapy
    2. TNF-α alpha antagonist
Exclusion Criteria
  1. Has undergone an ileostomy, colostomy, or has known fixed symptomatic stenosis of the intestine.
  2. Has active or latent tuberculosis (TB).
  3. Has had a prior exposure to vedolizumab or a history of hypersensitivity or allergies to vedolizumab, natalizumab, efalizumab, or rituximab.
  4. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist during screening or prior to the administration of study drug on Day 1.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Vedolizumab 300 mgVedolizumab IVVedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2 and 6 during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)From first dose of study drug up to 24 weeks after the last dose (up to 70 weeks)

AE was defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with the treatment. AE can therefore be any unfavourable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of a drug, whether or not it is considered related to the drug. A SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in significant disability or incapacity, was a congenital anomaly/birth defect or was a medically important event. An AESI (serious or nonserious) was one of scientific and medical concern specific to the compound or program.

Number of Participants With Adverse Drug Reactions (ADRs) and Unexpected ADRsFrom first dose of study drug up to 24 weeks after the last dose (up to 70 weeks)

An ADR was an AE for which there was at least a reasonable suspicion of a causal relationship between an AE and a suspected medicinal product. An unexpected ADR was an ADR with the nature, severity, or outcome which was not consistent with the product insert.

Secondary Outcome Measures
NameTimeMethod
Percentage of UC Participants With Clinical Response at Weeks 14, 30 and 46At Weeks 14, 30 and 46

Clinical response for UC participants was defined as decrease in Simple Clinical Colitis Activity Index (SCCAI) of greater than and equal to (\>=) 3 from baseline or by physician assessment of clinical response. The SCCAI consists of five colitis activity symptom items (bowel frequency per day, bowel frequency per night, urgency of defecation, blood in stool, and general well-being) along with an assessment of extracolonic manifestations. Bowel frequency per night is scored on a 0-2 scale and General well-being is scored on a 0-4 scale. The other 3 symptom scores are scored on a 0-3 scale. 1 point each is added for the presence of any extracolonic manifestation (i.e., arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The total overall possible scoring range was 0-19 with increasing scores being indicative of more colitis activity.

Percentage of CD Participants With Clinical Response at Weeks 14, 30 and 46At Weeks 14, 30 and 46

Clinical response for CD participants was defined as decrease in Harvey Bradshaw Index (HBI) of \>= 3 points from baseline. HBI was composed of five clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools/day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. The score \< 5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and \>16 severe disease. A higher score indicated a worse outcome.

Percentage of UC Participants With Clinical Remission at Weeks 14, 30 and 46At Weeks 14, 30 and 46

Clinical remission for UC participants was defined as decrease in SCCAI of less than and equal to (\<=) 2 with no individual score \> 1. The SCCAI consists of five colitis activity symptom items (bowel frequency per day, bowel frequency per night, urgency of defecation, blood in stool, and general well-being) along with an assessment of extracolonic manifestations. Bowel frequency per night is scored on a 0-2 scale and General well-being is scored on a 0-4 scale. The other 3 symptom scores are scored on a 0-3 scale. 1 point each is added for the presence of any extracolonic manifestation (i.e., arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The total overall possible scoring range was 0-19 with increasing scores being indicative of more colitis activity.

Percentage of CD Participants With Clinical Remission at Weeks 14, 30 and 46At Weeks 14, 30 and 46

Clinical remission for CD participants was defined as HBI of \<= 4. HBI was composed of five clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools/day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. The score \< 5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and \>16 severe disease. A higher score indicated a worse outcome.

Percentage of UC and CD Participants Who Discontinued VedolizumabFrom first dose of study drug up to Week 46

Vedolizumab discontinuation was defined as ceasing vedolizumab, or a treatment gap \>= 90 days between consecutive doses.

Percentage of UC Participants With Mucosal Healing at Week 46At Week 46

Mucosal healing was based on endoscopic evidence of no inflammation and healing of the mucosa as defined by a Mayo endoscopic sub-score of \<=1 point. Full Mayo Score evaluated ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic sub-score) ranged from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 were considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe, with higher scores indicated more severe disease.

Percentage of CD Participants With Mucosal Healing at Week 46At Week 46

Mucosal healing was based on endoscopic evidence of no inflammation and healing of the mucosa as defined by a Simple Endoscopic Score for Crohn Disease (SES-CD) 0-2 or SES-CD \<=4 and at least a 2-point reduction from baseline with no sub-score \>1. SES-CD assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables was scored from 0 to 3, with the sum of scores for each variable ranging from 0 to 15 yielding a total SES-CD score of 0-60, where higher scores indicated more severe disease.

Percentage of UC Participants With Endoscopic Response at Week 46At Week 46

Endoscopic response was defined as decrease in Mayo endoscopic sub-score of \>=1 point in UC participants. Full Mayo Score evaluated ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic sub-score) ranges from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 are considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe, where higher scores indicated more severe disease.

Percentage of CD Participants With Endoscopic Response at Week 46At Week 46

Endoscopic response was defined as \> 50% decrease in SES-CD in CD participants. SES-CD assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables was scored from 0 to 3, with the sum of scores for each variable ranged from 0 to 15 yielding a total SES-CD score of 0-60, where higher scores indicated more severe disease.

Change From Baseline in Patient-reported Quality of Life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]) Scores at Weeks 14, 30, and 46Baseline, Weeks 14, 30 and 46

The SIBDQ was a valid and reliable instrument used to assess quality of life in adult participants with Inflammatory Bowel Disease (IBD). It was a 10-item questionnaire that included questions on 4 domains of health-related quality of life (HRQoL): bowel systems, emotional function, social function, and systemic function and was scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). A total SIBDQ score was calculated by summing the scores from each domain; the total SIBDQ score ranged from 10 (poor HRQoL) to 70 (optimum HRQoL). Higher values of SIBDQ represented a better quality of life.

Trial Locations

Locations (17)

Banglore Medical College & Research Institute

🇮🇳

Bangalore, Karnatka, India

Deccan College of Medical Sciences

🇮🇳

Hyderabad, India

Asian Institute of Gastroenterology

🇮🇳

Hyderabad, Telangana, India

Gastroplus Digestive Disease Centre Pvt.Ltd

🇮🇳

Ahmedabad, Gujarat, India

Osmania General Hospital

🇮🇳

Hyderabad, India

Surat Institute of Digestive Sciences

🇮🇳

Surat, Gujarat, India

Dayanand Medical College and Hospital

🇮🇳

Ludhiana, Punjab, India

Yashoda Hospitals

🇮🇳

Secunderabad, Telangana, India

VGM Hospital- Institute of Gastroenterology

🇮🇳

Coimbatore, Tamilnadu, India

Dr. Ram Manohar Lohia Hospita Hospital

🇮🇳

New Delhi, Delhi, India

Maulana Azad Medical college & Associated G B Pant Hospital

🇮🇳

New Delhi, Delhi, India

Institute of Gastroenterology and Liver Disease Dispur Hospitals

🇮🇳

Guwahati, Assam, India

Indira Gandhi Institute of Medical Sciences

🇮🇳

Patna, Bihar, India

Government General Hospital

🇮🇳

Guntur, Andhra Pradesh, India

Midas Multispeciality Hospital

🇮🇳

Nagpur, Maharashtra, India

King George's Medical University

🇮🇳

Lucknow, Uttar Pradesh, India

All India Institute of Medical Sciences

🇮🇳

New Delhi, Delhi, India

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