Alagille SyndromePhase 2IMAGINENCT02047318
An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Subjects With Alagille Syndrome (ALGS)
A Phase 2 study testing LUM001 (Maralixibat) in people with Alagille Syndrome, run by Mirum Pharmaceuticals, Inc. at 3 sites in United Kingdom.
Trial summary
The purpose of this extension study is to determine the long-term safety and tolerability of an investigational treatment (LUM001 also known as Maralixibat) in children with ALGS who have completed participation in a core LUM001 treatment protocol. Read more about this study
- Who is it for?
- Ages 12 months to 18 years
- Conditions the study is for
- Alagille Syndrome
- What is being tested?
- LUM001 (Maralixibat)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 20 Dec 2013to 17 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Participation for an individual patient is expected to be approximately 72 weeks.
Patients who complete 72 weeks of treatment may be eligible to receive treatment for up to 52 weeks during the follow-up treatment period and patients who completed the 124 weeks of treatment may be eligible to enter the additional long-term follow-up period.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
Leeds Teaching Hospital NHS Trust
Leeds, West Yorkshire, LS1 3EX
Kings College Hospital
London, SE5 9RS
About this study
Official title: A Multicentre Extension Study to Evaluate the Long-Term Safety and Durability of the Therapeutic Effect of LUM001 Also Known as Maralixibat (MRX), an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome
The purpose of this extension study is to determine the long-term safety and tolerability of an investigational treatment (LUM001 also known as Maralixibat) in children with ALGS who have completed participation in a core LUM001 treatment protocol. Efficacy will be assessed by evaluating the effect of LUM001 on pruritus, biochemical markers of pruritus, as well as biochemical markers of cholestasis and liver disease.
- Conditions
- Alagille Syndrome
- Being tested
- LUM001 (Maralixibat)
- Medical subject headings
- Alagille Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LUM001 (Maralixibat)Drug
Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 560 micrograms per kilogram (mcg/kg).
| Study group | Role | What they receive |
|---|---|---|
| LUM001 (Maralixibat) | Experimental | LUM001 also known as Maralixibat (MRX) administered orally up to twice each day Receives: Drug: LUM001 (Maralixibat) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From MRX Baseline to Week 48 in Fasting sBA Levels
The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.
Measured: MRX baseline to Week 48
Secondary outcomes (15)
Change From MRX Baseline Over Time in Fasting sBA Levels
This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Pruritus
This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Pruritus
This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score
This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Alkaline Phosphatase
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.
Measured: MRX baseline to end of treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Alanine Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Alanine Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Aspartate Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.
Measured: MRX baseline to End of treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Gamma Glutamyltransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.
Measured: MRX baseline to Week 48
Change From MRX Baseline Over Time in Total and Direct Bilirubin
This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results.
Measured: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study start20 Dec 2013
- Primary completion17 Jun 2020
- Study completion17 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alagille SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirum Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Mirum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047318
- Sponsor's protocol ID
- LUM001-303
- Other IDs
- 2013-003832-54
- Acronym
- IMAGINE
- Status last verified
- Nov 2021
- First submitted
- 23 Jan 2014
- Last updated
- 19 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Extension Study to Evaluate the Long-Term Safety and Durability of the Therapeutic Effect of LUM001 Also Known as Maralixibat (MRX), an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome
- ClinicalTrials.gov ID
- NCT02047318
- Acronym / sponsor ID
- IMAGINE / LUM001-303
- Conditions
- Alagille Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Mirum Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Dec 2013 (actual)
- Primary completion
- 17 Jun 2020 (actual)
- Study completion
- 17 Jun 2020 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Posted 19 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this extension study is to determine the long-term safety and tolerability of an investigational treatment (LUM001 also known as Maralixibat) in children with ALGS who have completed participation in a core LUM001 treatment protocol. Efficacy will be assessed by evaluating the effect of LUM001 on pruritus, biochemical markers of pruritus, as well as biochemical markers of cholestasis and liver disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LUM001 (Maralixibat) | Experimental | Drug: LUM001 (Maralixibat)LUM001 also known as Maralixibat (MRX) administered orally up to twice each day |
Who may qualify
- Ages
- 12 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LUM001 (Maralixibat)Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 560 micrograms per kilogram (mcg/kg). | Drug | LUM001 (Maralixibat) |
Primary outcome
Change From MRX Baseline to Week 48 in Fasting sBA Levels
Time frame: MRX baseline to Week 48
The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.
15 secondary outcomes
Change From MRX Baseline Over Time in Fasting sBA Levels
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Pruritus
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Pruritus
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Alkaline Phosphatase
Time frame: MRX baseline to end of treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Alanine Aminotransferase
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Alanine Aminotransferase
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Aspartate Aminotransferase
Time frame: MRX baseline to End of treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Gamma Glutamyltransferase
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin
Time frame: MRX baseline to Week 48
Change From MRX Baseline Over Time in Total and Direct Bilirubin
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Mirum
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LUM001 (Maralixibat) in people with Alagille Syndrome, run by Mirum Pharmaceuticals, Inc. at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From MRX Baseline to Week 48 in Fasting sBA Levels (time frame: MRX baseline to Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Nov 2021.