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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03602560

Recruitment Status : Completed

First Posted : July 27, 2018

Results First Posted : May 31, 2022

Last Update Posted : August 2, 2022

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

CymaBay Therapeutics, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Primary Biliary Cholangitis
Interventions	Drug: seladelpar 5-10 mg Drug: seladelpar 10 mg Drug: Placebo
Enrollment	265

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Seladelpar 5-10 mg	Seladelpar 10 mg	Placebo
Arm/Group Description	seladelpar 5-10 mg: Seladelpar 5 mg...	seladelpar 10 mg: Seladelpar 10 mg ...	Placebo: One capsule daily for doub...
Arm/Group Description	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 for double-blind period.	Placebo: One capsule daily for double-blind period.
Period Title: Overall Study
Started	89	89	87
Completed	1	1	1
Not Completed	88	88	86

Baseline Characteristics

Arm/Group Title		Seladelpar 5-10 mg	Seladelpar 10 mg	Placebo	Total
Arm/Group Description		seladelpar 5-10 mg: Seladelpar 5 mg...	seladelpar 10 mg: Seladelpar 10 mg ...	Placebo: One capsule daily for doub...	Total of all reporting groups
Arm/Group Description		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: 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: 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 of all reporting groups
Overall Number of Baseline Participants		89	89	87	265
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	89 participants	89 participants	87 participants	265 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	75 84.3%	73 82.0%	73 83.9%	221 83.4%
	>=65 years	14 15.7%	16 18.0%	14 16.1%	44 16.6%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	89 participants	89 participants	87 participants	265 participants
	Female	82 92.1%	83 93.3%	85 97.7%	250 94.3%
	Male	7 7.9%	6 6.7%	2 2.3%	15 5.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	89 participants	89 participants	87 participants	265 participants
	American Indian or Alaska Native	1 1.1%	0 0.0%	0 0.0%	1 0.4%
	Asian	4 4.5%	8 9.0%	5 5.7%	17 6.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 1.1%	4 4.5%	2 2.3%	7 2.6%
	White	83 93.3%	77 86.5%	80 92.0%	240 90.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1.Primary Outcome


Title	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
Description	Percentage of Participants with Response to Composite Endpoint of ALP ...
Description	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.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Seladelpar 5-10 mg	Seladelpar 10 mg	Placebo
Arm/Group Description:	seladelpar 5-10 mg: Seladelpar 5 mg...	seladelpar 10 mg: Seladelpar 10 mg ...	Placebo: One capsule daily for doub...
Arm/Group Description:	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 for double-blind period.	Placebo: One capsule daily for double-blind period.
Overall Number of Participants Analyzed	56	55	56
Measure Type: Count of Participants Unit of Measure: Participants
	32 57.1%	43 78.2%	7 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	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).

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 5-10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	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).

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

2.Secondary Outcome


Title	Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3
Description	The response was defined by normalized ALP levels (ALP ≤1.0 ...
Description	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.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Seladelpar 5-10 mg	Seladelpar 10 mg	Placebo
Arm/Group Description:	seladelpar 5-10 mg: Seladelpar 5 mg...	seladelpar 10 mg: Seladelpar 10 mg ...	Placebo: One capsule daily for doub...
Arm/Group Description:	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 for double-blind period.	Placebo: One capsule daily for double-blind period.
Overall Number of Participants Analyzed	56	55	56
Measure Type: Count of Participants Unit of Measure: Participants
	3 5.4%	15 27.3%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Two-sided p-value for each pair-wise comparison was based on the CMH test adjusted for both randomization stratification variables (ALP level: <350 U/L and 350 U/L; pruritus NRS: <4 and 4). Breslow-Day test was used to check the homogeneity of treatment effects across stratum.

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 5-10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Two-sided p-value for each pair-wise comparison is based on the Cochran Mantel Haenszel test adjusted for both randomization stratification variables (ALP level: < 350 U/L and >= 350 U/L; pruritus NRS: < 4 and >= 4). Breslow-Day test is used to check the homogeneity of treatment effects across stratum.

Statistical Test of Hypothesis	P-Value	0.0839
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

3.Secondary Outcome


Title	Change From Baseline in Pruritus NRS for Subjects With Baseline NRS ≥4 at Month 3
Description	Pruritus Numerical Rating Scale (NRS) used to rate the intensity of th...
Description	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.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Seladelpar 5-10 mg	Seladelpar 10 mg	Placebo
Arm/Group Description:	seladelpar 5-10 mg: Seladelpar 5 mg...	seladelpar 10 mg: Seladelpar 10 mg ...	Placebo: One capsule daily for doub...
Arm/Group Description:	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 for double-blind period.	Placebo: One capsule daily for double-blind period.
Overall Number of Participants Analyzed	17	18	18
Mean (Standard Deviation) Unit of Measure: score on a scale
	-1.95 (2.226)	-3.01 (1.952)	-1.44 (1.831)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Change from baseline is estimated by an analysis of covariance (ANCOVA) model with treatment group (including 3 levels: Placebo, Initial Dose 5mg, and Initial Dose 10 mg) and randomization ALP stratification as factors, and baseline as a covariate. The p-value for the interaction between treatment and stratum is 0.7595, hence the interaction is dropped from the model.

Statistical Test of Hypothesis	P-Value	0.0164
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.59
	Confidence Interval	(2-Sided) 95% -2.87 to -0.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Seladelpar 5-10 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Change from baseline is estimated by an analysis of covariance (ANCOVA) model with treatment group (including 3 levels: Placebo, Initial Dose 5mg, and Initial Dose 10 mg) and randomization ALP stratification as factors, and baseline as a covariate. The p-value for the interaction between treatment and stratum is 0.7595, hence the interaction is dropped from the model.

Statistical Test of Hypothesis	P-Value	0.4781
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95% -1.77 to 0.84
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Seladelpar 5/10 mg		Seladelpar 10 mg		Placebo
Arm/Group Description	Seladelpar 5/10 mg in this double-b...		Seladelpar 10 mg in this double-bli...		Placebo in this double-blinded stud...
Arm/Group Description	Seladelpar 5/10 mg in this double-blinded study		Seladelpar 10 mg in this double-blinded study		Placebo in this double-blinded study
All-Cause Mortality
	Seladelpar 5/10 mg		Seladelpar 10 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/89 (0.00%)		0/89 (0.00%)		0/87 (0.00%)
Serious Adverse Events Serious Adverse Events
	Seladelpar 5/10 mg		Seladelpar 10 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/89 (3.37%)		1/89 (1.12%)		3/87 (3.45%)
Blood and lymphatic system disorders
Leukocytosis ^† 1	1/89 (1.12%)	1	0/89 (0.00%)	0	0/87 (0.00%)	0
Gastrointestinal disorders
Rectal polyp ^† 1	0/89 (0.00%)	0	0/89 (0.00%)	0	1/87 (1.15%)	1
Infections and infestations
Cellulitis ^† 1	0/89 (0.00%)	0	1/89 (1.12%)	1	0/87 (0.00%)	0
Pyelonephritis acute ^† 1	0/89 (0.00%)	0	0/89 (0.00%)	0	1/87 (1.15%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoid cystic carcinoma ^† 1	1/89 (1.12%)	1	0/89 (0.00%)	0	0/87 (0.00%)	0
Nervous system disorders
Cognitive disorder ^† 1	1/89 (1.12%)	1	0/89 (0.00%)	0	0/87 (0.00%)	0
Partial seizures ^† 1	0/89 (0.00%)	0	0/89 (0.00%)	0	1/87 (1.15%)	1
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3.0%
	Seladelpar 5/10 mg		Seladelpar 10 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/89 (61.80%)		58/89 (65.17%)		62/87 (71.26%)
Eye disorders
Dry eye ^† 1	3/89 (3.37%)	3	3/89 (3.37%)	3	2/87 (2.30%)	2
Gastrointestinal disorders
Abdominal distension ^† 1	1/89 (1.12%)	1	3/89 (3.37%)	4	3/87 (3.45%)	3
Abdominal pain upper ^† 1	8/89 (8.99%)	9	6/89 (6.74%)	6	3/87 (3.45%)	3
Constipation ^† 1	5/89 (5.62%)	5	3/89 (3.37%)	3	2/87 (2.30%)	2
Diarrhoea ^† 1	4/89 (4.49%)	4	4/89 (4.49%)	6	4/87 (4.60%)	5
Dry mouth ^† 1	5/89 (5.62%)	5	1/89 (1.12%)	1	0/87 (0.00%)	0
Dyspepsia ^† 1	3/89 (3.37%)	3	4/89 (4.49%)	4	3/87 (3.45%)	3
Gastrooesophageal reflux disease ^† 1	1/89 (1.12%)	1	3/89 (3.37%)	3	0/87 (0.00%)	0
Nausea ^† 1	5/89 (5.62%)	6	7/89 (7.87%)	8	4/87 (4.60%)	5
Vomiting ^† 1	0/89 (0.00%)	0	3/89 (3.37%)	3	3/87 (3.45%)	3
General disorders
Asthenia ^† 1	0/89 (0.00%)	0	3/89 (3.37%)	3	0/87 (0.00%)	0
Fatigue ^† 1	2/89 (2.25%)	2	4/89 (4.49%)	4	8/87 (9.20%)	8
Infections and infestations
Nasopharyngitis ^† 1	3/89 (3.37%)	3	2/89 (2.25%)	2	2/87 (2.30%)	2
Sinusitis ^† 1	2/89 (2.25%)	2	1/89 (1.12%)	1	5/87 (5.75%)	5
Upper respiratory tract infection ^† 1	6/89 (6.74%)	7	4/89 (4.49%)	4	2/87 (2.30%)	2
Urinary tract infection ^† 1	2/89 (2.25%)	2	5/89 (5.62%)	5	0/87 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	5/89 (5.62%)	5	4/89 (4.49%)	4	5/87 (5.75%)	5
Back pain ^† 1	2/89 (2.25%)	2	4/89 (4.49%)	5	3/87 (3.45%)	3
Muscle spasms ^† 1	1/89 (1.12%)	2	3/89 (3.37%)	3	1/87 (1.15%)	1
Musculoskeletal chest pain ^† 1	0/89 (0.00%)	0	3/89 (3.37%)	3	0/87 (0.00%)	0
Nervous system disorders
Headache ^† 1	5/89 (5.62%)	5	7/89 (7.87%)	8	1/87 (1.15%)	1
Psychiatric disorders
Insomnia ^† 1	1/89 (1.12%)	1	4/89 (4.49%)	4	0/87 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	4/89 (4.49%)	4	2/89 (2.25%)	2	4/87 (4.60%)	4
Skin and subcutaneous tissue disorders
Pruritus ^† 1	3/89 (3.37%)	4	10/89 (11.24%)	11	11/87 (12.64%)	16
Pruritus generalised ^† 1	3/89 (3.37%)	3	3/89 (3.37%)	3	3/87 (3.45%)	3
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Elaine Watkins, DO, MSPH, Vice President of Clinical Development
Organization:	CymaBay Therapeutics, Inc.
Phone:	510-293-8800
EMail:	medinfo@cymabay.com

Layout table for additonal information

Responsible Party:	CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT03602560
Other Study ID Numbers:	CB8025-31735
First Submitted:	July 18, 2018
First Posted:	July 27, 2018
Results First Submitted:	March 23, 2022
Results First Posted:	May 31, 2022
Last Update Posted:	August 2, 2022

To Top