Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Participants with Cholestatic Pruritus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mirum Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

17 Feb 2025 → ongoing

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of maralixibat versus placebo to reduce the severity of pruritus

Secondary objectives 1

1. To evaluate the efficacy of maralixibat versus placebo to reduce total sBA (serum bile acid) levels

Conditions and MedDRA coding

Cholestatic Pruritus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Informed consent and assent (as applicable)
2. Age ≥6 months at time of baseline visit
3. Diagnosis of rare cholestatic liver disease with cholestatic pruritus based on the following: a. Chronic liver biochemical abnormalities (>90 days) and/or pathological evidence of progressive liver disease. Total sBA (...) is required. b. Persistent pruritus (>90 days). An average worst-daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) score (...) weeks of the screening period leading to the baseline visit. Participants with the following rare diseases will be enrolled in the study: (...)
4. Completion of at (...) valid daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) entries during (...) of the screening period, leading to the baseline visit. Each week should (...) (morning and evening) entries.

Exclusion criteria 10

1. Diagnosis of (...)
2. Active atopic dermatitis or other non-cholestatic diseases associated with pruritus that are not controlled by standard treatment and that may interfere with the severity assessment of cholestasis-associated pruritus
3. Decompensated cirrhosis or complications of cirrhosis (e.g., esophageal or gastric variceal bleeding in the last 6 months, high-risk esophageal or gastric varices [e.g., large, coiled, occupying >1/3 of the esophageal lumen, red varices or red signs], ascites, hepatic encephalopathy, hepatorenal syndrome). Patients with compensated cirrhosis with preserved hepatic synthetic function (see Exclusion Criterion #6) and absence of complications are eligible.
4. Suspected or proven cholangiocarcinoma or hepatocellular carcinoma
5. Unstable and/or serious medical disease that is likely to impair the ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy (e.g., any active malignancy including hematological malignancy, end-stage heart failure, active infection, acute and chronic diarrhea). Exceptionally, previous history of malignancy, adequately treated/in remission, that in opinion of investigator and medical monitor does not impact participant safety and participation in the study, may be allowed. The investigator should contact the medical monitor to discuss these cases and seek approval before the screening period.
6. Laboratory results during the screening visit as follows: Platelet count (...); albumin (...); INR (...) (after intravenous or subcutaneous supplementation of vitamin K); total bilirubin: for participants <18 years of age: total bilirubin (...), for participants ≥18 years of age: total bilirubin (...); ALT: for participants <18 years of age: ALT (...), for participants ≥18 years of age: ALT (...)
7. Presence of any other disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, including bile salt metabolism in the intestine (e.g., clinically relevant inflammatory bowel disease involving the terminal ileum), per investigator discretion
8. Use of an IBAT inhibitor within 8 weeks prior to the screening visit
9. Use of any other investigational medication within 30 days or 5 times the half-life, whichever is greater, prior to the screening visit
10. History of liver transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the average worst Observer-rated Itch-Reported Outcome (ItchRO[Obs]) severity score from baseline through Weeks 13–20. The baseline average worst ItchRO(Obs) score is defined as the 2-week average worst ItchRO(Obs) severity score prior to the first dose of the study drug, where the worst ItchRO(Obs) severity score is defined as the higher of the morning severity score and evening severity score.

Secondary endpoints 5

1. Overall population: Change from baseline to average of Week (...) and Week (...) in total sBA (...)
2. Overall population: Percentage of days through Weeks (...) with pruritus improvement (worst ItchRO(Obs) score <1 (...)
3. (...): Change in the average worst-daily ItchRO(Obs) severity score from baseline through Weeks (...). The baseline average worst-daily ItchRO(Obs) score is defined as the (...)-week average worst-daily ItchRO(Obs) severity score prior to the first dose of the study drug.
4. (...): Change from baseline to average of Week (...) and Week (...) in total sBA (...)
5. (...): Percentage of days through Weeks (...) with pruritus improvement (worst-daily ItchRO[Obs] score <1 (...)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mirum Pharmaceuticals Inc.

Sponsor organisation

Mirum Pharmaceuticals Inc.

Address

950 Tower Lane Suite 300

City

Foster City

Postcode

94404-2171

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

5 EU/EEA countries · 12 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 99 files

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

Application history

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