Trial Outcomes & Findings for ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA) (NCT NCT03602560)

Last Updated: 2022-08-02

Results Overview

Percentage of Participants with Response to Composite Endpoint of ALP \<1.67 × Upper Limit of Normal \[ULN\], ≥15% reduction in ALP, and total bilirubin ≤ ULN) at Month 3. The mITT analysis set included all randomized subjects who received at least one study drug dose. The primary endpoint was analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted for both randomization stratification variables (ALP level: \<350 U/L and 2:350 U/L; pruritus NRS: \<4 and 2:4). The CMH tests were performed for the comparison of 10 mg versus placebo and 5 mg/10 mg versus placebo separately.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

265 participants

Primary outcome timeframe

Month 3

Results posted on

2022-08-02

Participant Flow

Participant milestones

Participant milestones
Measure	Seladelpar 5-10 mg seladelpar 5-10 mg: Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.	Seladelpar 10 mg seladelpar 10 mg: Seladelpar 10 mg for double-blind period.	Placebo Placebo: One capsule daily for double-blind period.
Overall Study STARTED	89	89	87
Overall Study COMPLETED	1	1	1
Overall Study NOT COMPLETED	88	88	86

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Seladelpar 5-10 mg n=89 Participants seladelpar 5-10 mg: Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study	Seladelpar 10 mg n=89 Participants seladelpar 10 mg: Seladelpar 10 mg for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label safety study. Subjects will continue the seladelpar dose (10 mg) received during the double-blinded study	Placebo n=87 Participants Placebo: One capsule daily for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects on placebo will be re-randomized to initiate seladelpar at 5 or 10 mg once daily	Total n=265 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	75 Participants n=99 Participants	73 Participants n=107 Participants	73 Participants n=206 Participants	221 Participants n=7 Participants
Age, Categorical >=65 years	14 Participants n=99 Participants	16 Participants n=107 Participants	14 Participants n=206 Participants	44 Participants n=7 Participants
Sex: Female, Male Female	82 Participants n=99 Participants	83 Participants n=107 Participants	85 Participants n=206 Participants	250 Participants n=7 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	6 Participants n=107 Participants	2 Participants n=206 Participants	15 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Asian	4 Participants n=99 Participants	8 Participants n=107 Participants	5 Participants n=206 Participants	17 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	4 Participants n=107 Participants	2 Participants n=206 Participants	7 Participants n=7 Participants
Race (NIH/OMB) White	83 Participants n=99 Participants	77 Participants n=107 Participants	80 Participants n=206 Participants	240 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants

PRIMARY outcome

Timeframe: Month 3

Population: mITT Population. The Modified Intent-to-Treat (mITT) set includes any subject who is randomized into the study and receives at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Seladelpar 5-10 mg n=56 Participants seladelpar 5-10 mg: Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.	Seladelpar 10 mg n=55 Participants seladelpar 10 mg: Seladelpar 10 mg for double-blind period.	Placebo n=56 Participants Placebo: One capsule daily for double-blind period.
Percentage of Participants With Response to Composite Endpoint of ALP <1.67 × Upper Limit of Normal [ULN], ≥15% Reduction in ALP, and Total Bilirubin ≤ ULN) at Month 3	32 Participants	43 Participants	7 Participants

SECONDARY outcome

Timeframe: Month 3

Population: mITT Population. The Modified Intent-to-Treat (mITT) set includes any subject who is randomized into the study and receives at least one dose of study drug.

The response was defined by normalized ALP levels (ALP ≤1.0 × ULN) at endpoint. The mITT analysis set included all randomized subjects who received at least one study drug dose.

Outcome measures

Outcome measures
Measure	Seladelpar 5-10 mg n=56 Participants seladelpar 5-10 mg: Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.	Seladelpar 10 mg n=55 Participants seladelpar 10 mg: Seladelpar 10 mg for double-blind period.	Placebo n=56 Participants Placebo: One capsule daily for double-blind period.
Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3	3 Participants	15 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 3

Population: mITT Population. The Modified Intent-to-Treat (mITT) set includes any subject who is randomized into the study and receives at least one dose of study drug.

Pruritus Numerical Rating Scale (NRS) used to rate the intensity of the worst itching you experienced in the past 24 hours from no itching to worst possible itching by selecting a number from 0 to 10 on Itch Scale. Zero means no itching and 10 means worst imaginable itching. The analysis will be limited to those subjects in the mITT analysis set with a baseline NRS ≥ 4.

Outcome measures

Outcome measures
Measure	Seladelpar 5-10 mg n=17 Participants seladelpar 5-10 mg: Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.	Seladelpar 10 mg n=18 Participants seladelpar 10 mg: Seladelpar 10 mg for double-blind period.	Placebo n=18 Participants Placebo: One capsule daily for double-blind period.
Change From Baseline in Pruritus NRS for Subjects With Baseline NRS ≥4 at Month 3	-1.95 score on a scale Standard Deviation 2.226	-3.01 score on a scale Standard Deviation 1.952	-1.44 score on a scale Standard Deviation 1.831

Adverse Events

Seladelpar 5/10 mg

Serious events: 3 serious events

Other events: 55 other events

Deaths: 0 deaths

Seladelpar 10 mg

Serious events: 1 serious events

Other events: 58 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Seladelpar 5/10 mg n=89 participants at risk Seladelpar 5/10 mg in this double-blinded study	Seladelpar 10 mg n=89 participants at risk Seladelpar 10 mg in this double-blinded study	Placebo n=87 participants at risk Placebo in this double-blinded study
Blood and lymphatic system disorders Leukocytosis	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Rectal polyp	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/87 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Cellulitis	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Pyelonephritis acute	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/87 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoid cystic carcinoma	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Nervous system disorders Cognitive disorder	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Nervous system disorders Partial seizures	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/87 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.

Other adverse events

Additional Information

Elaine Watkins, DO, MSPH, Vice President of Clinical Development

CymaBay Therapeutics, Inc.

Phone: 510-293-8800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Seladelpar 5/10 mg n=89 participants at risk Seladelpar 5/10 mg in this double-blinded study	Seladelpar 10 mg n=89 participants at risk Seladelpar 10 mg in this double-blinded study	Placebo n=87 participants at risk Placebo in this double-blinded study
Eye disorders Dry eye	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.3% 2/87 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Abdominal distension	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Abdominal pain upper	9.0% 8/89 • Number of events 9 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	6.7% 6/89 • Number of events 6 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Constipation	5.6% 5/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.3% 2/87 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Diarrhoea	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 6 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.6% 4/87 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Dry mouth	5.6% 5/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Dyspepsia	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Nausea	5.6% 5/89 • Number of events 6 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	7.9% 7/89 • Number of events 8 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.6% 4/87 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Gastrointestinal disorders Vomiting	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
General disorders Asthenia	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
General disorders Fatigue	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	9.2% 8/87 • Number of events 8 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Nasopharyngitis	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.3% 2/87 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Sinusitis	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	5.7% 5/87 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Upper respiratory tract infection	6.7% 6/89 • Number of events 7 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.3% 2/87 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Infections and infestations Urinary tract infection	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	5.6% 5/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 5/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	5.7% 5/87 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Musculoskeletal and connective tissue disorders Back pain	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Musculoskeletal and connective tissue disorders Muscle spasms	1.1% 1/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/87 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/89 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Nervous system disorders Headache	5.6% 5/89 • Number of events 5 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	7.9% 7/89 • Number of events 8 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	1.1% 1/87 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Psychiatric disorders Insomnia	1.1% 1/89 • Number of events 1 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	0.00% 0/87 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 4/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	2.2% 2/89 • Number of events 2 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	4.6% 4/87 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Skin and subcutaneous tissue disorders Pruritus	3.4% 3/89 • Number of events 4 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	11.2% 10/89 • Number of events 11 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	12.6% 11/87 • Number of events 16 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.
Skin and subcutaneous tissue disorders Pruritus generalised	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/89 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.	3.4% 3/87 • Number of events 3 • An AE will be recorded any time after the time of signed ICF and captured until this double-blinded study's last study visit, up to 1 year.