Maralixibat chloride for Cholestatic pruritus

Inclusion criteria

• {"criterion_text":"- Informed consent and assent (as applicable)\n- Willingness (participant or caregiver) to comply with all study visits and requirements through the end of the study\n- Age ≥6 months at time of baseline visit\n- Diagnosis of 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 >2× ULN is required. b. Persistent pruritus (>90 days). An average worst daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) score ≥1.5 during the 2 consecutive weeks of the screening period leading to the baseline visit. If both instruments are administered, a score ≥1.5 is required only for ItchRO(Obs). Participants with the following diseases will be enrolled in the study: Any liver disease, including but not limited to the following: Alpha-1 antitrypsin deficiency, ARC syndrome, BA, Caroli’s disease, ciliopathies, chronic viral hepatitis, hepatic sarcoidosis, idiopathic amyloidosis, IgG4-related sclerosing cholangitis, ischemic cholangiopathy, metabolic disorders, nonalcoholic fatty liver disease, post–liver transplant cholestasis (including patients with ALGS, PBC, PFIC, or PSC who have had liver transplant), secondary sclerosing cholangitis.\n- Completion of at least 10 valid daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) entries during 2 consecutive weeks of the screening period, leading to the baseline visit. If both instruments are administered, the completion criterion is required only for ItchRO(Obs).\n- If taking antipruritics or ursodeoxycholic acid, the participant has to be on a stable dosing regimen (i.e., same dose and frequency in the 30 days prior to the screening visit and will continue this dosing regimen up to Week 40 [adjustment for body weight is allowed]).\n- Non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use at least an acceptable method of contraception during the study and for 30 days following the last dose of the study drug. Females of childbearing potential must have a negative pregnancy test result.\n- Access to email or telephone for scheduled participant contacts and access to smart phone or tablet for PROs\n- Ability to read and/or understand the questionnaires (both caregivers and participants ≥9 years of age)\n- For participants ≤18 years of age: Access to consistent caregiver(s) during the study"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of ALGS, ICP, PBC, PFIC, or PSC with native liver.\n- Pregnant or nursing\n- Known intolerance/hypersensitivity to maralixibat or its excipients\n- History of nonadherence to medical regimens, unreliability, medical condition, mental instability, or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures\n- Clinically relevant alcohol use disorder or drug abuse within 12 weeks of screening\n- 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\n- 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.\n- Suspected or proven cholangiocarcinoma or hepatocellular carcinoma\n- 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.\n- Laboratory results during the screening visit as follows: a) Platelet count <70,000/mm3. Patients with any condition that further increases bleeding risk (e.g., recent clinically relevant bleeding event [6 months], recent major surgery [12 weeks], anticoagulant use, platelet function disorders) are excluded. b) Albumin <30 g/L c) INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K) d) Total bilirubin >10 mg/dL e) ALT >10× ULN\n- 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\n- Use of an IBAT inhibitor within 8 weeks prior to the screening visit\n- Use of any other investigational medication within 30 days or 5 times the half-life, whichever is greater, prior to the screening visit"}

Primary endpoints

• {"endpoint_text":"- Mean 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.","definition_or_measurement_approach":"Change from baseline to Weeks 13–20 in the average worst Observer-rated Itch-Reported Outcome (ItchRO[Obs]) severity score; baseline defined as the 2-week average worst ItchRO(Obs) prior to first dose. The worst score is the higher of morning and evening severity scores; endpoint is mean change from baseline through Weeks 13–20."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline to average of Week 12 and Week 20 in total sBA","definition_or_measurement_approach":"Change from baseline to the average of Week 12 and Week 20 in total serum bile acids (sBA) levels."}
• {"endpoint_text":"- Percentage of days through Weeks 13–20 with pruritus improvement (worst ItchRO(Obs) score <1 or decrease from baseline of ≥1)","definition_or_measurement_approach":"Proportion (%) of days during Weeks 13–20 on which pruritus improvement is observed, defined as worst ItchRO(Obs) score <1 or a decrease from baseline of ≥1."}
• {"endpoint_text":"- Proportion of participants with ≥50% reduction from baseline to average of Week 12 and Week 20 in sBA levels","definition_or_measurement_approach":"Proportion of participants achieving ≥50% reduction in sBA from baseline to the average of Week 12 and Week 20."}
• {"endpoint_text":"- Mean change in the average worst ItchRO(Pt) severity score from baseline through Weeks 13–20. The baseline average worst ItchRO(Pt) score is defined as the 2-week average worst ItchRO(Pt) severity score prior to the first dose of the study drug.","definition_or_measurement_approach":"Mean change from baseline through Weeks 13–20 in the average worst patient-reported ItchRO(Pt) severity score; baseline defined as the 2-week average worst ItchRO(Pt) prior to first dose."}

France

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

07-07-2025

Processing Time Days

361

Number Of Sites

3

Number Of Participants

7

Italy

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

11-07-2025

Processing Time Days

365

Number Of Sites

3

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

277

Number Of Sites

1

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

09-07-2025

Processing Time Days

308

Number Of Sites

3

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

09-10-2025

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

15

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Mirum Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon (Lr) Limited

Responsibilities

code: 4

Name

Suvoda LLC

Responsibilities

code: 3

Name

Medidata Solutions Inc.

Responsibilities

code: 7

Third parties

• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Travel services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Slope.io Inc.","duties_or_roles":"Provider of scanners for lab samples tracking at sites","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ePRO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Marken LLP","duties_or_roles":"Direct to patient IP shipment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Edetek Inc.","duties_or_roles":"code: 10","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Etymax Limited","duties_or_roles":"Translation services","organisation_type":"Pharmaceutical company"}