Trial Outcomes & Findings for Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE) (NCT NCT04270682)

Last Updated: 2024-10-28

Results Overview

Primary Analysis of Change from Baseline in Urine 23S-Pentol (Natural Log-Transformed) during the Two Double-blind Periods- Paired T-test

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

19 participants

Primary outcome timeframe

Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Results posted on

2024-10-28

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence AB Patients in the adult cohort participated in a randomized, double-blind, placebo-controlled, 2 period × 2-treatment crossover study with rescue medication and open-label run-in to assess the efficacy and safety of CDCA. Patients randomized to sequence AB received blinded 250 mg CDCA TID for DB1 and Placebo TID for DB2. Open-Label CDCA 250 mg TID: Adult cohort patients received open-label 250 mg CDCA TID during the run-in and washout periods of the study or as rescue medication during the double-blind periods, if needed, based on clinical symptoms. Rescue Medication CDCA 250 mg TID: CDCA 250 mg TID was provided as rescue medication during the double-blind periods, if needed, based on laboratory results.	Sequence BA Patients in the adult cohort participated in a randomized, double-blind, placebo-controlled, 2 period × 2-treatment crossover study with rescue medication and open-label run-in to assess the efficacy and safety of CDCA. Patients randomized to sequence BA received blinded Placebo TID for DB1 and 250 mg CDCA TID for DB2. Open-Label CDCA 250 mg TID: Adult cohort patients received open-label 250 mg CDCA TID during the run-in and washout periods of the study or as rescue medication during the double-blind periods, if needed, based on clinical symptoms. Rescue Medication CDCA 250 mg TID: CDCA 250 mg TID was provided as rescue medication during the double-blind periods, if needed, based on laboratory results.	Pediatric Cohort Pediatric cohort patients (≥1 month and \<16 years) participated in a 24-week, open-label cohort with an 8-week titration period and a 16-week treatment period at the tolerated dose. CDCA Weight-Based Dose TID: Patients in the pediatric cohort completed a weight-based dose titration to a tolerated dose and maintained that tolerated dose for the remainder of the study. Pediatric cohort dosing of CDCA was not to exceed an equivalent dose of 750 mg/day.
Overall Study STARTED	6	7	5
Overall Study COMPLETED	6	7	4
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence AB n=6 Participants Patients in the adult cohort will participate in a randomized, double-blind, placebo-controlled, 2 period × 2-treatment crossover study with rescue medication and open-label run-in to assess the efficacy and safety of CDCA. Patients randomized to sequence AB will receive blinded CDCA TID for 4 weeks or until open-label rescue medication criteria are triggered Blinded CDCA 250 mg TID: Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment. Placebo: Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment. Open-Label CDCA 250 mg TID: Adult cohort patients will receive open-label 250 mg CDCA TID during the run-in and washout periods of the study or as rescue medication during the double-blind periods, if needed, based on clinical symptoms.	Sequence BA n=7 Participants Patients in the adult cohort will participate in a randomized, double-blind, placebo-controlled, 2 period × 2-treatment crossover study with rescue medication and open-label run-in to assess the efficacy and safety of CDCA. Patients randomized to sequence BA will receive placebo TID for 4 weeks or until either the blinded and/or open-label rescue medication criteria are triggered. Blinded CDCA 250 mg TID: Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment. Placebo: Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment. Open-Label CDCA 250 mg TID: Adult cohort patients will receive open-label 250 mg CDCA TID during the run-in and washout periods of the study or as rescue medication during the double-blind periods, if needed, based on clinical symptoms. Rescue Medication CDCA 250 mg TID: CDCA 250 mg TID will be provided as rescue medication during the double-blind periods, if needed, based on laboratory results.	Pediatric Cohort n=5 Participants Pediatric cohort patients (≥1 month and \<16 years) will participate in a 24-week, open-label cohort with an 8-week titration period and a 16-week treatment period at the tolerated dose. CDCA Weight-Based Dose TID: Patients in the pediatric cohort will complete a weight-based dose titration to a tolerated dose and will maintain that tolerated dose for the remainder of the study. Pediatric cohort dosing of CDCA will not exceed an equivalent dose of 750 mg/day.	Total n=18 Participants Total of all reporting groups
Age, Customized Number Analyzed	43 years STANDARD_DEVIATION 7.4 • n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	38.6 years STANDARD_DEVIATION 11.73 • n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	8.2 years STANDARD_DEVIATION 3.96 • n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	29.9 years STANDARD_DEVIATION 3.9 • n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Sex: Female, Male Female	1 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	4 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	5 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	10 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Sex: Female, Male Male	5 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	3 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	8 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	1 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	2 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Race/Ethnicity, Customized White	5 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	3 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	5 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	13 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Race/Ethnicity, Customized Other	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	2 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	2 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	1 Participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	0 Participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	1 Participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Region of Enrollment United States	3 participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	4 participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	3 participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	10 participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.
Region of Enrollment Brazil	3 participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	3 participants n=7 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	2 participants n=5 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.	8 participants n=4 Participants • Thirteen of 14 enrolled participants (92.9%) were randomized and completed the study. One participant was enrolled, but was not randomized, and withdrew from the study.

PRIMARY outcome

Timeframe: Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Population: All adult cohort participants who were randomized and took at least one dose of randomized study medication.

Primary Analysis of Change from Baseline in Urine 23S-Pentol (Natural Log-Transformed) during the Two Double-blind Periods- Paired T-test

Outcome measures

Outcome measures
Measure	CDCA TID n=13 Participants Active: Contains 250 mg of Chenodiol (the non-proprietary name for CDCA). Open-label and blinded CDCA are the same drug product.	Placebo TID n=13 Participants Control: Placebo study medication is provided in the same form as blinded CDCA, as white film-coated 250-mg tablets with no CDCA.
Change From Baseline in Urine 23S-Pentol During the Two Double-Blind Periods Pooled Double Blind Baseline	7.18 natural log of ng/mL Standard Deviation 0.797	6.96 natural log of ng/mL Standard Deviation 1.076
Change From Baseline in Urine 23S-Pentol During the Two Double-Blind Periods Pooled last non missing postbaseline Double Blind record	7.45 natural log of ng/mL Standard Deviation 0.675	10.34 natural log of ng/mL Standard Deviation 0.788
Change From Baseline in Urine 23S-Pentol During the Two Double-Blind Periods Pooled change from baseline to last non missing postbaseline Double Blind record	0.20 natural log of ng/mL Standard Deviation 0.732	3.38 natural log of ng/mL Standard Deviation 1.111

SECONDARY outcome

Timeframe: Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Population: All adult cohort participants who were randomized and took at least one dose of randomized study medication, and who had been on CDCA for at least 2 months prior to the open-label run-in period.

Primary Analysis of Change from Baseline Plasma Cholestanol (Natural Log-transformed) at the End of the Two Double-Blind Periods- Paired T-test

Outcome measures

Outcome measures
Measure	CDCA TID n=7 Participants Active: Contains 250 mg of Chenodiol (the non-proprietary name for CDCA). Open-label and blinded CDCA are the same drug product.	Placebo TID n=7 Participants Control: Placebo study medication is provided in the same form as blinded CDCA, as white film-coated 250-mg tablets with no CDCA.
Change From Baseline Plasma Cholestanol During the Two Double-Blind Periods Pooled last non missing post baseline Double Blind record	1.10 natural log of μg/mL Standard Deviation 0.728	1.88 natural log of μg/mL Standard Deviation 0
Change From Baseline Plasma Cholestanol During the Two Double-Blind Periods Pooled change from baseline to last non missing post baseline Double Blind record	-0.12 natural log of μg/mL Standard Deviation 0.542	0.75 natural log of μg/mL Standard Deviation 0.865
Change From Baseline Plasma Cholestanol During the Two Double-Blind Periods Pooled Double Blind baseline	1.13 natural log of μg/mL Standard Deviation 0.791	1.14 natural log of μg/mL Standard Deviation 0.534

SECONDARY outcome

Timeframe: Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Population: All adult cohort participants who were randomized and took at least one dose of randomized study medication.

Primary Analysis of Change from Baseline Plasma 7αC4 (Natural Log-Transformed) During the Two Double-Blind Periods

Outcome measures

Outcome measures
Measure	CDCA TID n=13 Participants Active: Contains 250 mg of Chenodiol (the non-proprietary name for CDCA). Open-label and blinded CDCA are the same drug product.	Placebo TID n=13 Participants Control: Placebo study medication is provided in the same form as blinded CDCA, as white film-coated 250-mg tablets with no CDCA.
Change From Baseline Plasma 7αC4 During the Two Double-Blind Periods Pooled Double Blind baseline	4.02 natural log of ng/mL Standard Deviation 0.519	4.00 natural log of ng/mL Standard Deviation 0.526
Change From Baseline Plasma 7αC4 During the Two Double-Blind Periods Pooled last non missing postbaseline Double Blind record	3.97 natural log of ng/mL Standard Deviation 0.572	7.60 natural log of ng/mL Standard Deviation 0.511
Change From Baseline Plasma 7αC4 During the Two Double-Blind Periods Pooled change from baseline to last non missing postbaseline Double Blind record	-0.08 natural log of ng/mL Standard Deviation 0.717	3.60 natural log of ng/mL Standard Deviation 0.742

SECONDARY outcome

Timeframe: Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Population: All adult cohort participants who were randomized and took at least one dose of randomized study medication.

Proportion of Participants Who Received Rescue Treatment during Two Double-Blind Periods - Prescott's Method

Outcome measures

Outcome measures
Measure	CDCA TID n=13 Participants Active: Contains 250 mg of Chenodiol (the non-proprietary name for CDCA). Open-label and blinded CDCA are the same drug product.	Placebo TID n=13 Participants Control: Placebo study medication is provided in the same form as blinded CDCA, as white film-coated 250-mg tablets with no CDCA.
Proportion of Participants Who Received Rescue Treatment During Two Double-Blind Periods Double Blind Period 1 Proportion of participants who required rescue medication, %	0 participants	2 participants
Proportion of Participants Who Received Rescue Treatment During Two Double-Blind Periods Double Blind Period 2 Proportion of participants who required rescue medication, %	1 participants	6 participants
Proportion of Participants Who Received Rescue Treatment During Two Double-Blind Periods Pooled Proportion of participants who required rescue medication, %	1 participants	8 participants

Adverse Events

CDCA

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Pediatric Cohort

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CDCA n=13 participants at risk Patients in the adult cohort ; blinded CDCA 250 mg TID in DB1 or DB2 Treatment-Emergent Adverse Events (TEAEs) were defined as those that start from Open-label Period 1 throughout the study, or existing AEs that worsen during or after Open-label Period 1.	Placebo n=13 participants at risk Patients in the adult cohort ; Placebo 250 mg TID in DB1 or DB2 Treatment-Emergent Adverse Events (TEAEs) were defined as those that start from Open-label Period 1 throughout the study, or existing AEs that worsen during or after Open-label Period 1.	Pediatric Cohort n=5 participants at risk Pediatric cohort patients (≥1 month and \<16 years) will participate in a 24-week, open-label cohort with an 8-week titration period and a 16-week treatment period at the tolerated dose.
General disorders Gait Disturbance	0.00% 0/13 • AEs (including SAEs) were captured from the time informed consent was signed to the patient's final visit. In addition, AEs (including SAEs) were to be collected for all patients via a follow-up phone call 30 (±7) days after the last dose of study medication to assess patient safety. Adult Cohort: 24 weeks duration Pediatric Cohort: 16 week duration * Symptoms described by the patient * Clinically significant changes in the patient's physical examination or other signs observed by the Investigator or medical staff * Test abnormalities (laboratory tests, ECG, X-rays, etc.) that reflect a change from baseline and/or that may result in changes in administration of study medication or in an alteration in medical care (diagnostic or therapeutic) * Conditions present at baseline that have either worsened or recurred following resolution	7.7% 1/13 • AEs (including SAEs) were captured from the time informed consent was signed to the patient's final visit. In addition, AEs (including SAEs) were to be collected for all patients via a follow-up phone call 30 (±7) days after the last dose of study medication to assess patient safety. Adult Cohort: 24 weeks duration Pediatric Cohort: 16 week duration * Symptoms described by the patient * Clinically significant changes in the patient's physical examination or other signs observed by the Investigator or medical staff * Test abnormalities (laboratory tests, ECG, X-rays, etc.) that reflect a change from baseline and/or that may result in changes in administration of study medication or in an alteration in medical care (diagnostic or therapeutic) * Conditions present at baseline that have either worsened or recurred following resolution	0.00% 0/5 • AEs (including SAEs) were captured from the time informed consent was signed to the patient's final visit. In addition, AEs (including SAEs) were to be collected for all patients via a follow-up phone call 30 (±7) days after the last dose of study medication to assess patient safety. Adult Cohort: 24 weeks duration Pediatric Cohort: 16 week duration * Symptoms described by the patient * Clinically significant changes in the patient's physical examination or other signs observed by the Investigator or medical staff * Test abnormalities (laboratory tests, ECG, X-rays, etc.) that reflect a change from baseline and/or that may result in changes in administration of study medication or in an alteration in medical care (diagnostic or therapeutic) * Conditions present at baseline that have either worsened or recurred following resolution

Other adverse events

Additional Information

Mirum Clinical Trials

Mirum Pharmaceuticals

Phone: 650-667-4085

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place