A Study of TAK-625 for the Treatment of Alagille Syndrome (ALGS)

An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-625 in the Treatment of Subjects With Alagille Syndrome

The main aim of the study is to check if TAK-625 improves symptoms of Alagille Syndrome (ALGS), side effect from the study treatment or TAK-625, and how much TAK-625 stays in their blood over time. This will help the study sponsor (Takeda) to work out the best dose to give people in the future.

The participants will be treated with TAK-625 for up to the end of study (about 34 months).

Participants will visit their study clinic 9 times from the start of study. After 9 times visits, participants will visit their study clinic every 12 weeks up to the end of study.

Study Overview

• Status: Completed
• Conditions: Alagille Syndrome (ALGS)
• Intervention / Treatment: Drug: TAK-625

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan
    • Kyoto University Hospital
  • Saitama, Japan
    • Saitama Prefectural Children's Medical Center
  • Ibaraki
    • Tsukuba, Ibaraki, Japan
      • University of Tsukuba Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Yokohamashi Tobu Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Miyagi Children's Hospital
  • Nara
    • Ikoma, Nara, Japan
      • Kindai University Nara Hospital
  • Osaka
    • Suita, Osaka, Japan
      • Osaka University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Juntendo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The participant is Japanese male or female with a body weight >=3.0 kilograms (kg) and who is >=1 month of age at the time of informed consent.
2. The participant is diagnosed with ALGS.

3. The participant has one or more of the following evidences of cholestasis:

   1. Total serum bile acid (sBA) >3^ upper limit of the normal range (ULN) for age.
   2. Direct bilirubin (conjugated) >1 mg/dL.
   3. Lipid soluble vitamin (LSV) deficiency otherwise unexplainable.
   4. Gamma-glutamyl transferase (GGT) >3^ ULN for age.
   5. Intractable pruritus explainable only by liver disease.
4. The participant is expected to have a consistent caregiver(s) for the duration of the study.
5. The participant has an access to phone for scheduled calls from study site.
6. Both a caregiver and participant above the age of assent are capable of reading and understanding the questionnaires.
7. Caregivers (and age-appropriate participants) must be willing and able to use an eDiary device during the study.
8. Caregivers (and age-appropriate participants) must complete at least 10 eDiary reports (morning or evening) during each of 2 consecutive weeks of the screening period (maximum possible reports=14 per week), even if the participant is an adult (over 18 years old).
9. Average daily score >2 on the ItchRO questionnaire (maximum possible daily score of 4) for 2 consecutive weeks in the screening period, prior to dosing. A daily score is the higher of the scores for the morning and evening ItchRO. The average daily score is the sum of all daily scores divided by the number of days the ItchRO was completed. Since it is difficult to evaluate pruritus in infants, participants <12 months of age at screening whose pruritus is unavoidably difficult to be evaluated are not necessarily required to meet the above score.

Exclusion Criteria:

1. The participant has chronic diarrhea requiring ongoing intravenous (IV) fluid or nutritional intervention.
2. The participant has a previous history of surgical interruption of the enterohepatic circulation.
3. The participant has a previous liver transplant.
4. The participant decompensated cirrhosis (ALT >15^ ULN, international normalized ratio [INR] >1.5 [unresponsive to vitamin K therapy], albumin <3.0 g/dL, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy).
5. The participant has a history or presence of other concomitant liver disease.
6. The participant has a 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 (eg, inflammatory bowel disease).
7. The participant has a history or presence of gallstones or kidney stones.
8. The participant has a possible malignant liver mass in imaging, including screening ultrasound.
9. The participant has cancers, except for in situ carcinoma, or cancers treated at least 5 years prior to screening with no evidence of recurrence.
10. The participant has received bile acid/lipid binding resins or IBAT inhibitors within 28 days prior to screening and throughout the trial.
11. The participant who has received sodium phenylbutyrate for less than 6 months at the initiation of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-625; TAK-625 200 mcg per kilogram, orally, once daily for 1 week. After that, TAK-625 400 mcg per kilogram, orally, once daily after Week 1.	Drug: TAK-625; TAK-625 200 mcg or 400 mcg per kilogram, orally, once daily; Other Names: Maralixibat chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Serum Bile Acid (sBA) Levels From Week 18 to Week 22	Change in fasting sBA levels from Week 18 to 22 was reported. Change was calculated as: observed value at Week 22- observed value at Week 18.	From Week 18 to Week 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting sBA Levels From Baseline to Week 18	Change in fasting sBA levels from baseline to Week 18 was reported. Change was calculated as: observed value at Week 18 - observed value at baseline (before dosing).	Baseline to Week 18
Change in Weekly Average Severity of Pruritus Measured by Itch Reported Outcome (ItchRO) (Observer Instrument [Obs]) From Baseline to Week 18	The ItchRO (Obs) scale measures severity of pruritus. The score on ItchRO (Obs) scale ranged from 0 to 4, where 0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe. A higher score indicated more severe pruritus. Weekly average severity of Pruritus is calculated based on daily maximum of morning and evening severity scores measured by ItchRO (Obs). Weekly average severity was calculated as the average of the daily maximum of morning and evening over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 18 (Day 120 to Day 126) - average value of baseline (Day -7 to Day -1).	Baseline to Week 18
Change in Weekly Average Morning Severity of Pruritus Measured by Itch Reported Outcome (ItchRO) (Observer Instrument [Obs]) From Baseline to Week 18	The ItchRO (Obs) scale measures severity of pruritus. The score on ItchRO (Obs) scale ranged from 0 to 4, where 0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe. A higher score indicated more severe pruritus. Weekly average morning severity was calculated as the average of the daily morning scores over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 18 (Day 120 to Day 126) - average value of baseline (Day -7 to Day -1).	Baseline to Week 18
Change in Weekly Average Severity of Pruritus Measured by ItchRO (Obs) From Week 18 to Week 22	The ItchRO (Obs) scale measures severity of pruritus. The score on ItchRO (Obs) scale ranged from 0 to 4, where 0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe. A higher score indicated more severe pruritus. Weekly average severity of Pruritus was calculated based on daily maximum of morning and evening severity scores measured by ItchRO (Obs). Weekly average severity were calculated as the average of the daily maximum of morning and evening over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 22 (Day 148 to Day 154) - average value of Week 18 (Day 120 to Day 126).	From Week 18 to Week 22
Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Obs) From Week 18 to Week 22	The ItchRO (Obs) scale measures severity of pruritus. The score on ItchRO (Obs) scale ranged from 0 to 4, where 0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe. A higher score indicated more severe pruritus. Weekly average morning severity was calculated as the average of the daily morning scores over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 22 (Day 148 to Day 154) - average value of Week 18 (Day 120 to Day 126).	From Week 18 to Week 22
Change in Weekly Average Severity of Pruritus Measured by ItchRO (Pt) From Baseline to Week 18	The ItchRO (Pt) scale measures severity of pruritus. The score on ItchRO (Pt) scale ranged from 0 to 4, where 0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy. A higher score indicated more severe pruritus. Weekly average severity of Pruritus was calculated based on daily maximum of morning and evening severity scores measured by ItchRO (Pt). Weekly average scores was calculated as the average of the daily maximum of morning and evening over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 18 (Day 120 to Day 126) - average value of baseline (Day -7 to Day -1).	Baseline to Week 18
Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) From Baseline to Week 18	The ItchRO (Pt) scale measures severity of pruritus. The score on ItchRO (Pt) scale ranged from 0 to 4, where 0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy. A higher score indicated more severe pruritus. Weekly average morning severity was calculated as the average of the daily morning scores over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 18 (Day 120 to Day 126) - average value of baseline (Day -7 to Day -1).	Baseline to Week 18
Change in Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels From Baseline to Week 18	Change in ALT and ALP levels from baseline to Week 18 were reported. Change was calculated as: observed value at Week 18 - observed value at baseline (before dosing).	Baseline to Week 18
Change in Bilirubin (Total and Direct) Levels From Baseline to Week 18	Change in bilirubin (total and direct) from baseline to Week 18 was reported. Change was calculated as: observed value at Week 18 - observed value at baseline (before dosing).	Baseline to Week 18
Change in Weekly Average Severity of Pruritus Measured by ItchRO (Pt) From Week 18 to Week 22	The ItchRO (Pt) scale measures severity of pruritus. The score on ItchRO (Pt) scale ranged from 0 to 4, where 0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy. A higher score indicated more severe pruritus. Weekly average severity of Pruritus was calculated based on daily maximum of morning and evening severity scores measured by ItchRO (Pt). Weekly average scores was calculated as the average of the daily maximum of morning and evening over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 22 (Day 148 to Day 154) - average value of Week 18 (Day 120 to Day 126).	From Week 18 to 22
Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) From Week 18 to Week 22	The ItchRO (Pt) scale measures severity of pruritus. The score on ItchRO (Pt) scale ranged from 0 to 4, where 0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy. A higher score indicated more severe pruritus. Weekly average morning severity was calculated as the average of the daily morning scores over the visit consisting of the 7 days on or before the scheduled Study Day (i.e., the sum of the scores divided by the number of non-missing scores). Change was calculated as: average value of Week 22 (Day 148 to Day 154) - average value of Week 18 (Day 120 to Day 126).	From Week 18 to 22
Change in ALT and ALP Levels From Week 18 to 22	Change in ALT and ALP from Week 18 to 22 was reported. Change was calculated as: observed value at Week 22 - observed value at Week 18.	From Week 18 to 22
Change in Bilirubin (Total and Direct) Levels From Week 18 to 22	Change in bilirubin (total and direct) from Week 18 to 22 was reported. Change was calculated as: observed value at Week 22 - observed value at Week 18.	From Week 18 to 22

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Actual): October 25, 2023
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Genetic Diseases, Inborn; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alagille Syndrome
• Other Study ID Numbers: TAK-625-3001; jRCT2051220098 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes