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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003138-99 | EudraCT Number |
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The study was withdrawn due to change of ownership of the study drug maralixibat. Future studies of maralixibat will be posted by Mirum Pharmaceuticals.
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The purpose of this study is to determine if the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Maralixibat (SHP625) | Experimental | Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks. |
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| Placebo | Placebo Comparator | Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maralixibat | Drug | Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) | Compare the percentage of participants on active treatment versus (vs.) placebo who meet response criteria which is defined as improvement in before midday (AM) Observer Itch Reported Outcome (ItchRO[Obs]) severity decrease from baseline demonstrated on at least 2 of the last 3 study visits. | Baseline up to Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA) | Compare the percentage of participants on active treatment versus (vs.) placebo who meet response criteria which is defined as improvement in average before midday (AM) Observer Itch Reported Outcome (ItchRO[Obs]) severity decrease from baseline and normalization or reduction from baseline sBA demonstrated on at least 2 of the last 3 study visits. |
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Key Inclusion Criteria:
Informed consent and assent (as applicable for participants less than or equal to (<=) 18 years per Institutional Review Board/Ethics Committee (IRB)/Ethics Committee (EC) as appropriate.
Male or female participants between the ages of 12 months and 18 years inclusive (primary cohort) or birth to 18 years inclusive (exploratory cohort) at time of consent, with a body weight greater than or equal to (>=) 5 kilogram (kg).
Cholestasis as manifested by total sBA greater than (>) 3*upper limit of normal (ULN)
An average AM ItchRO(Obs) score >= 1.5 during the 4 weeks leading to the baseline visit
Diagnosis of PFIC based on:
a. Primary cohort: i. Participants with 2 documented mutant alleles in ABCB11 (PFIC2); participants without bile salt export pump (BSEP) function (biallelic truncating mutations in ABCB11) will not be enrolled into the primary cohort. b. Exploratory cohort: i. Participants with PFIC1/3/4 or PFIC2 with biallelic truncating mutationsiii.Infants from birth to <12 months of age with PFIC ii. Participants with PFIC after internal or external (eg, PEBD) biliary diversion surgery with unsatisfactory pruritus control or where biliary diversion was reversed.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Mirum | Study Director |
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| Placebo | Drug | Placebo matching to maralixibat orally twice daily for 26 weeks. |
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| Baseline up to Week 26 |
| Normalization or Reduction From Baseline in Serum Bile Acids (sBA) | Compare the percentage of participants on active treatment vs. placebo with normalization or significant reduction from baseline in sBA. | Baseline up to Week 26 |
| Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score | Change over time in daily average ItchRO scores will be reported. | Baseline up to Week 26 |
| Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score | Change over time in AM ItchRO scores will be reported. | Baseline up to Week 26 |
| Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score | Change over time in PM ItchRO scores will be reported. | Baseline up to Week 26 |
| Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs]) | Compare the percentage of participants on active treatment vs. placebo of participants who experience disappearance of pruritus as measured by ItchRO(Obs). | Baseline up to Week 26 |
| Improvement in Height | Number of participants on active treatment vs. placebo with a height z-score change from baseline >0. | Baseline up to Week 26 |
| Improvement in Weight | Number of participants on active treatment vs. placebo with a weight z-score change from baseline >0. | Baseline up to Week 26 |
| Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference | Compare the change in nutritional status as measured by mid-arm circumference in participants on active treatment vs. placebo. | Baseline, Week 26 |
| Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold | Compare the change in nutritional status as measured by triceps skin fold in participants on active treatment vs. placebo. | Baseline, Week 26 |
| Change From Baseline in Clinician Scratch Scale (CSS) | Compare the change in Clinician Scratch Scale score in participants on active treatment vs. placebo. | Baseline, Week 26 |
| Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) | Compare the change from baseline of PedsQL in participants on active treatment vs. placebo. | Baseline, Week 26 |
| Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ) | Compare the change from baseline of CSHQ in participants on active treatment vs. placebo. | Baseline, Week 26 |
| Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT) | Number of participants whose ALT normalizes on treatment or has decreased >=50%. | Baseline up to Week 26 |
| Normalization or Meaningful Decrease From Baseline of Total Bilirubin | Number of participants whose total bilirubin normalizes on treatment or has decreased >=50%. | Baseline up to Week 26 |
| Change From Baseline in Biomarkers of Bile Acid Synthesis | Change from baseline in biomarkers of bile acid synthesis (serum 7 alpha-hydroxy-4-cholesten-3-one [C4]). | Baseline, Week 26 |
| Evaluate the safety of SHP625 | Adverse events, changes in vital signs, laboratory, and other safety parameters will be compared between participants on active treatment vs. placebo. | Baseline up to Week 26 |
| Plasma Levels of Maralixibat Over Time | Systemic concentrations of maralixibat in plasma will be assessed. | Baseline, Week 6, 10, 14, 18, 22 and 26 |
| ID | Term |
|---|---|
| C535933 | Cholestasis, progressive familial intrahepatic 1 |
| D002779 | Cholestasis |
| ID | Term |
|---|---|
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000722912 | maralixibat |
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