Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Multiple Center Study to Evaluate the Safety, Tolerability, and Efficacy of Seladelpar Administered for 24 Weeks in Adult Patients with Primary Sclerosing Cholangitis (PSC)
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Summary
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EudraCT number |
2019-001760-30 |
Trial protocol |
GB PL |
Global end of trial date |
09 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Oct 2021
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First version publication date |
03 Oct 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CB8025-21845
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND : Number: 142198 | ||
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Sponsors
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Sponsor organisation name |
CymaBay Therapeutics, Inc.
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Sponsor organisation address |
7575 Gateway Blvd, Suite 110, Newark, United States, 94560
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Public contact |
Mary Standen, CymaBay Therapeutics, Inc., +1 510 293-8800, mstanden@cymabay.com
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Scientific contact |
Elaine Watkins, CymaBay Therapeutics, Inc., +1 510 293-8800, ewatkins@cymabay.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Jan 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jan 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jan 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate the treatment effect of seladelpar on alkaline phosphatase (AP) in participants with PSC during the study period
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki and its revisions and the International Conference on Harmonisation (ICH) Harmonized Tripartite Guideline for Good Clinical Practice (GCP). The study was also in compliance with the applicable local regulatory requirements and laws of each country in which the study was conducted, as well as with any applicable guidelines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Nov 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
1
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted in 60 sites in Australia, Europe, Israel, and North America. Only 1 site in the U.S. enrolled. | ||||||||||||
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Pre-assignment
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Screening details |
On Day 1, participants were to be randomized into one of four treatment arms (seladelpar 5 mg, 10 mg, 25 mg, or placebo) in a 1:1:1:1 ratio. Participants stratification at randomization planned per UDCA use (Yes/No) and by averaged Screening total bilirubin values (≤ ULN vs > ULN but ≤ 2 × ULN) to ensure even distribution across treatment groups | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||
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Arms
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Arm title
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Placebo | ||||||||||||
Arm description |
Subjects received matched placebo capsules orally once daily for the study duration | ||||||||||||
Arm type |
Placebo | ||||||||||||
Investigational medicinal product name |
Seladelpar
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Investigational medicinal product code |
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Other name |
MBX-8025
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received matching placebo capsules orally once daily for the study duration
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study (overall period)
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Reporting group description |
Subjects received matched placebo capsules orally once daily for the study duration | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received matched placebo capsules orally once daily for the study duration | ||
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End point title |
Relative Change from Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 24 (Endpoint) [1] | ||||||||
End point description |
Relative (percent) change in alkaline phosphatase (ALP) from Baseline to Week 24
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End point type |
Primary
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End point timeframe |
Baseline, Week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study was terminated early therefore no statistical analyses was done |
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| Notes [2] - Analysis was not performed due to study termination |
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| No statistical analyses for this end point | |||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Upto week 24
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Adverse event reporting additional description |
There were no adverse events reported during the study treatment.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
22.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: The study was terminated early and subject’s laboratory values for ALT, AST, GGT, and ALP were slightly elevated at screening and remained essentially the same throughout treatment with slight variations over the 14 days of treatment with placebo. No Adverse Events were reported in the study. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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05 Jun 2019 |
Version 2.0
*Participants are stratified according to UDCA use (Yes/No) and by averaged Screening total bilirubin (TB) values (≤ ULN vs > ULN but ≤ 2 × ULN).
*In the Inclusion Criteria #3:
• Platelets were changed from ≥ 120 x 103/μL to ≥ 140 x 103/μL;
• Total bilirubin was changed from 2.5 mg/dL to 2.2 mg/dL (2 x ULN);
• Add an upper threshold for AP. The criterion is now AP ≥ 1.5 x ULN and ≤ 8 x ULN.
*In Inclusion Criteria #4
• Participants taking UDCA must be on a stable dose for 6 months rather than allowing subjects to make some dosing adjustments 8 weeks prior to screening.
*Exclusion Criteria # 3 was added to exclude patients with small-duct PSC.
*In Exclusion Criteria #10, the following criteria were added:
• Historical liver biopsy demonstrating cirrhosis (e.g., Ludwig Stage 4 or Ishak Stage ≥ 5);
• Current or prior history of decompensated liver disease, including ascites, hepatic encephalopathy, variceal bleeding or other clinical conditions consistent with cirrhosis and/or portal hypertension;
• FibroScan® > 14.4 kPa;
• Combined low platelet count (< 140 × 103/μL) with one or more of the following, Albumin < 3.5 g/dL, INR > 1.3 (not due to antithrombotic agent use), or total bilirubin > ULN.
*Exclusion Criteria #11 was added to exclude PSC patients whose AP, ALT, AST, or total bilirubin exhibit variability > 40% higher during Screening.
*Addition of test for C-terminal pro-peptide of type V collagen (PRO-C5).
*Addition of a second screening visit (Screening Visit 2).
*Addition of missing pruritis evaluation dispensing at Week 4.
*Addition of DILI safety monitoring criteria following the FDA Guidance for Industry: Drug Induced Injury, Premarket Clinical Evaluation.
*Addition of the additional stopping criteria for an individual participant
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| Only one patient was randomized into the study until the early study termination. On 25-NOV-2019 (Study Day 14) the subject received last dose of placebo. The early termination visit occurred on 09-JAN-2020 (study Day 59). | |||||||
