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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04130919




Registration number
NCT04130919
Ethics application status
Date submitted
16/10/2019
Date registered
18/10/2019
Date last updated
4/05/2021

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis
Scientific title
A Phase 2, Blinded, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of GS-4875 in Subjects With Moderately to Severely Active Ulcerative Colitis
Secondary ID [1] 0 0
2019-001430-33
Secondary ID [2] 0 0
GS-US-365-4237
Universal Trial Number (UTN)
Trial acronym
Falcon
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tilpisertib
Treatment: Drugs - Placebo

Experimental: Tilpisertib 300 mg - Participants will receive blinded tilpisertib 300 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Experimental: Tilpisertib 100 mg - Participants will receive blinded tilpisertib 100 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Placebo Comparator: Placebo - Participants will receive blinded tilpisertib placebo for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks.

Experimental: Open-label Treatment Phase - Based on the efficacy assessment results at Week 10, participants who do not achieve MCS response will have the option to receive open-label tilpisertib 300 mg for up to 50 weeks.


Treatment: Drugs: Tilpisertib
Tablets administered orally once daily

Treatment: Drugs: Placebo
Tablets administered orally once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants who Achieve Clinical Remission per Modified MCS at Week 10 - Clinical remission per modified MCS is defined as stool frequency subscore = 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore = 1.
Timepoint [1] 0 0
Week 10
Secondary outcome [1] 0 0
Percentage of Participants who Achieve Endoscopic Response at Week 10 - Endoscopic response is defined as an endoscopic subscore = 1.
Timepoint [1] 0 0
Week 10
Secondary outcome [2] 0 0
Percentage of Participants who Achieve MCS Response at Week 10 - MCS response is defined as a decrease from baseline of = 3 points and at least 30% in MCS, in addition to a = 1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore = 1.
Timepoint [2] 0 0
Week 10
Secondary outcome [3] 0 0
Percentage of Participants who Achieve MCS Remission at Week 10 - MCS remission is defined as a MCS score of = 2 and no individual subscore > 1.
Timepoint [3] 0 0
Week 10
Secondary outcome [4] 0 0
Percentage of Participants who Achieve Histologic Remission Based Upon the Geboes Scale at Week 10 - All the following must be met for histologic remission based upon the Geboes scale:
Grade 0 of = 0.3, Grade 1 of = 1.1, Grade 2a of = 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0. Lower values represent a better outcome.
Timepoint [4] 0 0
Week 10
Secondary outcome [5] 0 0
Percentage of Participants Experiencing Adverse Events
Timepoint [5] 0 0
First dose date up to 60 weeks plus 30 days
Secondary outcome [6] 0 0
Percentage of Participants Experiencing Laboratory Abnormalities
Timepoint [6] 0 0
First dose date up to 60 weeks plus 30 days

Eligibility
Key inclusion criteria
- Males, or non-pregnant, non-lactating females, at least 18 years of age based on the
date of the screening visit.

- UC of at least 3 months duration before randomization confirmed by endoscopy and
histology at any time in the past AND a minimum disease extent of 15 cm from the anal
verge. Documentation of endoscopy and histology consistent with the diagnosis of UC
must be available in the source documents prior to the initiation of screening.

- Moderately to severely active UC as determined during screening by a centrally read
endoscopy score = 2, a Rectal Bleeding subscore = 1, a Stool Frequency subscore = 1
and Physicians Global Assessment (PGA) of = 2 as defined by the Mayo Clinic Score;
total MCS must be between 6 and 12, inclusive.

- Previously demonstrated an inadequate response (primary non-response) or loss of
response (secondary non-response) to a tumor necrosis factor-alpha (TNFa) inhibitor
(ie, infliximab, adalimumab, golimumab, or biosimilars). The induction treatment
regimen resulting in inadequate response or loss of response should have been in
accordance with local prescribing information/guidelines or as outlined below.

- Infliximab: 5 mg/kg at Weeks 0, 2, and 6

- Adalimumab: 160 mg on Day 1 (given in 1 day or split over consecutive days),
followed by 80 mg 2 weeks later (Day 15), 40 mg 2 weeks later (Day 29) and every
2 weeks thereafter until Day 57

- Golimumab: 200 mg on Day 1 followed by 100 mg at Week 2

- May be receiving concomitant therapy for UC at the time of enrollment as specified in
the protocol, provided the dose prescribed has been stable as indicated prior to
randomization.

- Meet the following Tuberculosis (TB) screening criteria:

- No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1
of the following:

- A negative QuantiFERON test or equivalent assay reported by the central lab
at screening or within 90 days prior to randomization date. OR

- A history of fully treated active or latent TB according to local standard
of care. Investigator must verify adequate previous anti-TB treatment and
provide documentation; these individuals do not require QuantiFERON testing
and eligibility must be approved by the sponsor prior to enrollment in the
study. AND

- A chest radiograph (views as per local guidelines with the report or films
available for investigator review) taken at screening or within the 4 months
prior to randomization without evidence of active or latent TB infection.

- Laboratory assessments at screening within the following parameters:

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and total
bilirubin = 2 X ULN (upper limit of normal)

- Estimated glomerular filtration rate (eGFR) = 60 ml/min (1.0 mL/sec) as
calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Cystatin C formula as described in protocol.

- Hemoglobin = 8 g/dL (= 80 g/L)

- Absolute neutrophil count (ANC) = 1.5 × 10^3/µL (= 1.5 GI/L)

- Platelets = 100 × 10^3/µL (= 100 GI/L)

- White blood cells (WBC) = 3 × 10^3/µL (= 3 GI/L)

- Absolute lymphocyte count = 0.75 × 10^3/µL (= 0.75 GI/L)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Currently displaying clinical signs of acute severe colitis, fulminant colitis, or
toxic megacolon.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Coastal Digestive Health - Maroochydore
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
Emeritus Research - Melbourne
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3124 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Austria
State/province [13] 0 0
Innsbruck
Country [14] 0 0
Austria
State/province [14] 0 0
Vienna
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
France
State/province [16] 0 0
Clichy
Country [17] 0 0
France
State/province [17] 0 0
Dijon
Country [18] 0 0
France
State/province [18] 0 0
Grenoble
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Pierre-Benite
Country [21] 0 0
France
State/province [21] 0 0
Rennes
Country [22] 0 0
France
State/province [22] 0 0
Saint-Etienne
Country [23] 0 0
France
State/province [23] 0 0
Toulouse
Country [24] 0 0
France
State/province [24] 0 0
Vandoeuvre-les-Nancy Cedex
Country [25] 0 0
Germany
State/province [25] 0 0
Kiel
Country [26] 0 0
Germany
State/province [26] 0 0
Leipzig
Country [27] 0 0
Germany
State/province [27] 0 0
Minden
Country [28] 0 0
Italy
State/province [28] 0 0
Rozzano
Country [29] 0 0
Poland
State/province [29] 0 0
Szczecin
Country [30] 0 0
Poland
State/province [30] 0 0
Torun
Country [31] 0 0
Poland
State/province [31] 0 0
Wroclaw
Country [32] 0 0
Switzerland
State/province [32] 0 0
Bern
Country [33] 0 0
Switzerland
State/province [33] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to demonstrate the efficacy of tilpisertib (formerly
GS-4875) compared with placebo control in achieving clinical remission per modified Mayo
Clinic score (MCS) in adults with moderately to severely active ulcerative colitis (UC).
Trial website
https://clinicaltrials.gov/show/NCT04130919
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications