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Progressive Familial Intrahepatic Cholestasis (PFIC)Phase 3NCT03353454

A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)

A Phase 3 study testing Maralixibat in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages Up to 18 years
What is being tested?
Maralixibat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
25 Oct 2018to 15 Jun 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
  • 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.

Who cannot join

  • Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae.
  • History of surgical disruption of the enterohepatic circulation (applies to primary cohort only).
  • Liver transplant
  • Decompensated cirrhosis (international normalized ratio [INR] >1.5, albumin <30 gram per liter [g/L], history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy).
  • ALT >15*ULN at screening.
  • History or presence of other liver disease.
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  • History or 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 (example [eg], inflammatory bowel disease), per investigator discretion.
  • Liver mass on imaging
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Any prior cancer diagnosis except for in situ carcinoma or cancers treated within 5 years of the screening visit (Visit 0) with no evidence of recurrence.

About this study

Official title: Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)

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).

Being tested
Maralixibat, Placebo
Keywords
Cholestasis, Maralixibat, Mutation
Medical subject headings
Cholestasis, progressive familial intrahepatic 1, Cholestasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MaralixibatDrug

    Also called SHP625

    Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.

  • PlaceboDrug

    Placebo matching to maralixibat orally twice daily for 26 weeks.

Study groups in NCT03353454
Study groupRoleWhat they receive
Maralixibat (SHP625)ExperimentalParticipants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
Receives: Drug: Maralixibat
PlaceboPlacebo comparatorParticipants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to Week 26

Secondary outcomes (18)

  1. 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.

    Measured: Baseline up to Week 26

  2. 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.

    Measured: Baseline up to Week 26

  3. Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score

    Change over time in daily average ItchRO scores will be reported.

    Measured: Baseline up to Week 26

  4. Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score

    Change over time in AM ItchRO scores will be reported.

    Measured: Baseline up to Week 26

  5. Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score

    Change over time in PM ItchRO scores will be reported.

    Measured: Baseline up to Week 26

  6. 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).

    Measured: Baseline up to Week 26

  7. Improvement in Height

    Number of participants on active treatment vs. placebo with a height z-score change from baseline >0.

    Measured: Baseline up to Week 26

  8. Improvement in Weight

    Number of participants on active treatment vs. placebo with a weight z-score change from baseline >0.

    Measured: Baseline up to Week 26

  9. 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.

    Measured: Baseline, Week 26

  10. 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.

    Measured: Baseline, Week 26

  11. Change From Baseline in Clinician Scratch Scale (CSS)

    Compare the change in Clinician Scratch Scale score in participants on active treatment vs. placebo.

    Measured: Baseline, Week 26

  12. 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.

    Measured: Baseline, Week 26

  13. 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.

    Measured: Baseline, Week 26

  14. Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)

    Number of participants whose ALT normalizes on treatment or has decreased >=50%.

    Measured: Baseline up to Week 26

  15. Normalization or Meaningful Decrease From Baseline of Total Bilirubin

    Number of participants whose total bilirubin normalizes on treatment or has decreased >=50%.

    Measured: Baseline up to Week 26

  16. 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]).

    Measured: Baseline, Week 26

  17. 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.

    Measured: Baseline up to Week 26

  18. Plasma Levels of Maralixibat Over Time

    Systemic concentrations of maralixibat in plasma will be assessed.

    Measured: Baseline, Week 6, 10, 14, 18, 22 and 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2017
  2. Study start25 Oct 2018 (estimated)
  3. Primary completion15 Jun 2020 (estimated)
  4. Study completion15 Jun 2020 (estimated)

Why it stopped: The study was withdrawn due to change of ownership of the study drug maralixibat. Future studies of maralixibat will be posted by Mirum Pharmaceuticals.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03353454
Sponsor's protocol ID
SHP625-306
Other IDs
2017-003138-99, 2017
Status last verified
Mar 2019
First submitted
14 Nov 2017
Last updated
18 Mar 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Maralixibat in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) (time frame: Baseline up to Week 26). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03353454.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2019.

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