Home » Trials » SLCTR/2018/029


Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease -

SLCTR Registration Number

SLCTR/2018/029


Date of Registration

31 Aug 2018

The date of last modification

Aug 31, 2018



Application Summary


Scientific Title of Trial

Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease


Public Title of Trial

Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Crohn's Disease (Diversity1)


Disease of Health Condition(s) Studied

Crohn's Disease


Scientific Acronym

None


Public Acronym

DIVERSITY1


Brief title

Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Crohn's Disease


Universal Trail Number

None


Any other number(s) assigned to the trial and issuing authority

NCT02914561 (clinicaltrials.gov) 2016-001367-36 (EUCTR)


Trial Details


What is the research question being addressed?

What is the efficacy and safety of Filgotinib in the induction and maintenance treatment of moderately to severely active Ulcerative Colitis in biologic-naive and biologic-experienced participants?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Intervention(s) planned

Study sites Colombo North Teaching Hospital, Ragama Teaching Hospital Karapitiya, Galle Kandy Teaching Hospital, Kandy.

This is a combined Phase 3 double-blind, randomized, placebo-controlled studies to evaluate the efficacy and safety of filgotinib in the induction and maintenance of remission in subjects with moderately to severely active CD. The study is divided into 2 parts (induction study and maintenance study). Based on protocol eligibility criteria, subjects will be screened for enrollment in either Cohort A (biologic naïve patients) or Cohort B (biologic experienced patients).

Subjects who meet protocol eligibility criteria will be assigned to the respective Cohort and subsequently randomized in a blinded fashion in a 1:1:1 ratio to 1 of 3 treatments to the induction study as follows:

Treatment 1 (n = 220): filgotinib 200 mg and placebo-to-match (PTM) filgotinib 100 mg, once daily Treatment 2 (n = 220): filgotinib 100 mg and PTM filgotinib 200 mg, once daily Treatment 3 (n = 220): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily

The study medication will consist of 200 mg and 100 mg filgotinib tablets for oral administration, and PTM 200 mg and 100 mg filgotinib tablets for oral administration.

Subjects in Cohort A and B who complete the Induction Study and achieve either clinical remission by PRO2 (patient reported outcomes consisting of 2 items: abdominal pain severity and liquid stool frequency) or endoscopic response by SES-CD (Simple Endoscopic Score for Crohn's Disease) at Week 10 will be re-randomized into the Maintenance Study at Week 11. Subjects who achieve neither clinical remission by PRO2 nor endoscopic response at Week 10 will have the option to enter a separate Long-Term Extension (LTE) study (Gilead Study GS-US-419-3896).

Standard management be offered to all arms given that the allowed concomitant medication(s) for Crohn’s Disease (CD) must be maintained at a stable dose for the noted time without dosing alteration or discontinuation. The allowed medications for CD are as follows:

• Oral 5-ASA compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must be stable for the first 10 weeks after randomization

• Azathioprine, 6-MP, or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose must be stable for the first 10 weeks after randomization

• Oral corticosteroid therapy (prednisone prescribed at a stable dose = 30 mg/day or budesonide prescribed at a stable dose of = 9 mg/day) provided the dose prescribed has been stable for 2 weeks prior to randomization; dose must be stable for the first 14 weeks after randomization

• Antibiotics for the treatment of CD (eg, metronidazole, ciprofloxacin) provided the dose prescribed has been stable for 2 weeks prior to randomization. Dose must remain stable for the first 10 weeks after randomization. Subjects who are on cyclic therapy must continue their standard low-dose regimen without change for the first 10 weeks after randomization.


Inclusion criteria

  1. Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
  2. Documented diagnosis of Crohn's disease (CD) with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum, as determined by histopathology and endoscopic assessment
  3. Moderately to severely active Crohn's disease (CD) as determined by a) CDAI total score between 220 and 450 inclusive b) PRO2 score consisting of abdominal pain >2 (on CDAI scale of 0 to 3) OR daily stool frequency >4 c) Evidence of active disease as measured by SES-CD, (Total score >6, OR If disease is limited to the ileum and/or right colon, a combined score >4 in these two segments)
  4. Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents: corticosteroids, immunomodulators, tumor necrosis factor alpha (TNFa) antagonists, or vedolizumab

Exclusion criteria

  1. Current complications of Crohn's disease (CD) such as symptomatic strictures, severe rectal/anal stenosis, fistulae, short bowel syndrome, etc.
  2. Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
  3. Active tuberculosis (TB) or history of latent TB that has not been treated
  4. Use of any prohibited concomitant medications as described in the study protocol (details available at the SLCTR)


Primary outcome(s)

Induction Study:

  1. Proportion of Participants Achieving Clinical Remission by Patient Reported Outcomes (PRO2) at Week 10

  2. Proportion of Participants Achieving Endoscopic Response at Week 10

Maintenance Study:

  1. Proportion of Participants Achieving Clinical Remission by PRO2 at Week 58

  2. Proportion of Participants Achieving Endoscopic Response at Week 58


Primary outcome(s) - Time of assessment(s)

Induction Study:

  1. Proportion of Participants Achieving Clinical Remission by Patient Reported Outcomes (PRO2) at Week 10 [ Time Frame: Week 10 ]

  2. Proportion of Participants Achieving Endoscopic Response at Week 10 [ Time Frame: Week 10 ]

Maintenance Study:

  1. Proportion of Participants Achieving Clinical Remission by PRO2 at Week 58 [ Time Frame: Week 58 ]

  2. Proportion of Participants Achieving Endoscopic Response at Week 58 [ Time Frame: Week 58 ]


Secondary outcome

Induction Study:

  1. Proportion of Participants Achieving Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10

  2. Proportion of Participants Achieving Both Clinical Remission by PRO2 and endoscopic response at Week 10 (Composite Endpoint)

  3. Pharmacokinetic Concentrations of Filgotinib and its Metabolite GS-829845

Maintenance Study:

  1. Proportion of Participants Achieving Clinical Remission by CDAI at Week 58

  2. Proportion of Participants Achieving Sustained Clinical Remission by PRO2 at Weeks 10 and 58

  3. Proportion of Participants Achieving Both Clinical Remission by PRO2 and Endoscopic Response at Week 58 (Composite Endpoint)

  4. Proportion of Participants Achieving 6 Month Corticosteroid-Free Remission by PRO2 at Week 58

  5. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845


Secondary outcome(s) - Time of assessment(s)

Induction Study:

  1. Proportion of Participants Achieving Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10

  2. Proportion of Participants Achieving Both Clinical Remission by PRO2 and endoscopic response at Week 10 (Composite Endpoint)

  3. Pharmacokinetic Concentrations of Filgotinib and its Metabolite GS-829845

Maintenance Study:

  1. Proportion of Participants Achieving Clinical Remission by CDAI at Week 58

  2. Proportion of Participants Achieving Sustained Clinical Remission by PRO2 at Weeks 10 and 58

  3. Proportion of Participants Achieving Both Clinical Remission by PRO2 and Endoscopic Response at Week 58 (Composite Endpoint)

  4. Proportion of Participants Achieving 6 Month Corticosteroid-Free Remission by PRO2 at Week 58

  5. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845



Target number/sample size

Total of 70 subjects from Sri Lanka (hree arms and 23 subjects in each arm)


Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, France, Georgia, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sri Lanka, Sweden, Switzerland, Taiwan, Province of China, Ukraine, United Kingdom, United States


Anticipated start date

2018-09-01


Anticipated end date

2019-12-31


Recruitment status

Pending


State of ethics review approval

Approved by Ethics Review Committee, Faculty of Medicine, University of Kelaniya on 13 March 2018 (Ref: p\280\12\27)


Funding source

Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA 94404, USA



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Prof Arjuna de Silva
Consultant Physician
Research Room, Ward 21, Professorial Unit, Colombo North Teaching Hospital, Ragama 11010, Sri Lanka

Mob: + 94-777572379

apdesilva@kln.ac.lk

Contact Person for Public Queries

Prof Arjuna de Silva
Consultant Physician
Research Room, Ward 21, Professorial Unit, Colombo North Teaching Hospital, Ragama 11010, Sri Lanka

Mob: + 94-777572379

apdesilva@kln.ac.lk


Primary study sponsor/organization

Gilead Sciences, Inc
Gilead Clinical Study Information Center
333 Lakeside Drive Foster City, CA 94404, USA
+1-833-445-3230

GileadClinicalTrials@gilead.com

Secondary study sponsor (If any)

None