A study to evaluate efficacy and safety of an investigational drug named volixibat in patients with itching caused by primary biliary cholangitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mirum Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

11 Jul 2022 → ongoing

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504660-41-00

EudraCT number

2021-001389-39

ClinicalTrials.gov

NCT05050136

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Dose response, Efficacy, Therapy

To evaluate the efficacy of volixibat versus placebo for the treatment of pruritus in participants with PBC as measured by the change in the Adult ItchRO tool in participants with PBC

Secondary objectives 4

1. 1.To evaluate the efficacy of volixibat versus placebo on the improvement of markers of cholestasis in participants with PBC.
2. 2.To evaluate the efficacy of volixibat versus placebo for the treatment of pruritus in participants with PBC
3. 3.To evaluate safety and tolerability of volixibat versus placebo in participants with PBC-associated pruritus
4. 4.To evaluate QoL in participants with PBC-associated pruritus treated with volixibat versus placebo

Conditions and MedDRA coding

Cholestatic Pruritus in Patients with Primary Biliary Cholangitis (PBC).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study.
2. 2. Male or female, age ≥18 years at the screening visit
3. 3. Confirmed diagnosis of PBC in line with the AASLD guidelines.
4. 4. UDCA and anti-pruritic medication use will be allowed if meeting additional criteria.
5. 5. Qualified pruritus associated with PBC as assessed by Adult ItchRO.

Exclusion criteria 5

1. 1. Chronic pruritus of other etiology that may interfere with the severity assessment of PBC-related pruritus
2. 2.Evidence of decompensated cirrhosis or complications of cirrhosis (e.g., variceal bleeding or untreated esophageal/gastric varices, ascites, hepatic encephalopathy, hepatorenal syndrome).
3. 3. Current symptomatic cholelithiasis or inflammatory gallbladder disease.
4. 4. History of small bowel surgery/resection impacting the terminal ileum that may disrupt the enterohepatic circulation.
5. 5. Evidence, history, or suspicion of other liver diseases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in Adult ItchRO score comparing baseline with the average of the weekly averaged daily itch scores to the end of the double-blind study treatment.

Secondary endpoints 9

1. 1. Mean change in sBA levels
2. 2. Mean change in total bilirubin levels
3. 3. Mean change in ALP levels
4. 4.Change in Primary Biliary Cholangitis Quality of Life Measure (PBC-40) from baseline through end of double blind study treatment
5. 5. Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue score from baseline to end of double blind study treatment
6. 6. Change in PROMIS sleep score from baseline to end of double blind study treatment
7. 7. Proportion of participants achieving a reduction of ≥ 2 points in the weekly averaged daily Adult ItchRO score from baseline to end of double blind study treatment
8. 8. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), ECIs, and AEs that lead to discontinuation of study drug
9. 9. Incidence of clinically relevant laboratory abnormalities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mirum Pharmaceuticals Inc.

Sponsor organisation

Mirum Pharmaceuticals Inc.

Address

989 East Hillsdale Boulevard

City

Foster City

Postcode

94404-2113

Country

United States

Scientific contact point

Organisation

Mirum Pharmaceuticals Inc.

Contact name

Mirum Clinical Lead

Public contact point

Organisation

Mirum Pharmaceuticals Inc.

Contact name

Mirum Clinical Lead

Third parties 12

Locations

6 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 129 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications