A Study of TAK-625 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC)

An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-625 in the Treatment of Subjects With Progressive Familial Intrahepatic Cholestasis

The main aim of the study is to check if TAK-625 improves symptoms of Progressive Familial Intrahepatic Cholestasis (PFIC), 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 15 times from the start of study. After 15 times visits, participants will visit their study clinic every 12 weeks up to the end of study.

Study Overview

• Status: Completed
• Conditions: Progressive Familial Intrahepatic Cholestasis (PFIC)
• Intervention / Treatment: Drug: TAK-625

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • 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
  • Okayama-ken
    • Tsuyama, Okayama-ken, Japan
      • Tsuyama Chuo 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 kg and who is >=1 month of age at the time of informed consent.
2. The participant has a cholestasis as manifested by total serum bile acid (sBA) >=3^ upper limit of the normal range (ULN) (applies to the primary cohort only).
3. The participant has an average morning ItchRO (Obs) score >=1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Week 0/Visit 2). 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.
4. The caregiver has completed at least 21 valid* morning ItchRO (Obs) entries during 4 consecutive weeks of the screening period, leading to the baseline visit (Week 0/Visit 2) (*valid=completed and not answered as "I don't know"; the maximum allowed invalidreports=7, no more than 2 invalid reports during the last 7 days before the baseline visit [Week 0/Visit 2]).

5. The participant has a diagnosis of progressive familial intrahepatic cholestasis (PFIC) based on:

   Chronic cholestasis as manifested by persistent (>6 months*) pruritus in addition to biochemical abnormalities and/or pathological evidence of progressive liver disease. (* =<6 months is acceptable for participants <12 months of age).

   AND

   For Primary cohort:

   a) The participant has a genetic testing result consistent with disease-causing variation in ABCB11 (PFIC2), based on a genotyping.

   For Supplemental cohort:

   1. The participant has a genetic testing results consistent with disease causing variation in ATP8B1 (PFIC1), ABCB4 (PFIC3), or tight junction protein 2 gene (TJP2) (PFIC4), based on a genotyping.
   2. The participant has a PFIC phenotype without a known mutation or with another known mutation not described above.
   3. The PFIC participant has internal or external biliary diversion surgery history, and the internal or external biliary diversion surgery was reversed.
6. The participant (whenever possible) and caregiver are able to be contacted by phone for scheduled remote visits (participant contacts [phone calls]).
7. Both a caregiver and participant above the age of assent are capable of reading and understanding the questionnaires.
8. The same caregiver should be contacted during this study. The ItchRO (Obs) should be completed by the same caregiver for consistency during this study, even if the participant is an adult (over 18 years old).

Exclusion Criteria:

1. The diagnosed with PFIC2 due to ABCB11 mutation that predicts complete absence of BSEP function due to the type of ABCB11 mutation (t-PFIC2), based on a genotyping (applies to the primary cohort only).
2. The participant has a diagnosis of benign recurrent intrahepatic cholestasis indicated by a history of intermittent cholestasis with no disease progression.
3. The participant has a current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
4. The participant has a previous history of surgical interruption of the enterohepatic circulation (applies to the primary cohort only).
5. The participant with chronic diarrhea requiring intravenous (IV) fluid or nutritional intervention and/or its sequelae at screening or during the 6 months prior to screening.
6. The participant has a history of liver transplant or currently requires imminent liver transplant.
7. The participant with decompensated cirrhosis (international normalized ratio [INR] >1.5, and/or albumin <30 g/L, history, or presence of clinically significant ascites, and/or variceal hemorrhage, and/or encephalopathy).
8. The participant has an alanine aminotransferase (ALT) or total serum bilirubin (TSB) level >15^ ULN at screening.
9. The participant has other liver disease.
10. The participant has 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), per investigator discretion.
11. The participant has a possible malignant liver mass in imaging, including screening ultrasound.
12. The participant has received bile acid, lipid binding resins or ileal bile acid transporter (IBAT) inhibitors within 28 days prior to screening and throughout the trial.
13. 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-625, Primary cohort; TAK-625 orally, twice daily (BID) for 4 weeks as Dose Escalation Period. The dose in Dose Escalation Period will be increased weekly, 150 mcg/kilograms (kg), 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg. After Dose Escalation Period, TAK-625 600 mcg/kg (or maximum tolerated dose [MTD]), orally, BID up to study completion.	Drug: TAK-625; TAK-625 orally, twice daily (BID); Other Names: Maralixibat chloride
Experimental: TAK-625, Supplemental cohort; TAK-625 orally, twice daily (BID) for 4 weeks as Dose Escalation Period. The dose in Dose Escalation Period will be increased weekly, 150 mcg/kilograms (kg), 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg. After Dose Escalation Period, TAK-625 600 mcg/kg (or maximum tolerated dose [MTD]), orally, BID up to study completion.	Drug: TAK-625; TAK-625 orally, twice daily (BID); Other Names: Maralixibat chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Average Morning Itch Reported Outcome (ItchRO) (Observer Instrument [Obs]) Severity Score Between Baseline and the Average of Week 15 Through Week 26	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. Average baseline morning ItchRO (Obs) scores were calculated as sum of the morning scores divided by number of morning scores for the 4-week (28 days) time periods (that is [i.e.], Day -28 to Day -1). Average morning ItchRO (Obs) scores Week 15 through Week 26 were calculated as the sum of the morning scores divided by the number of morning scores from Week 15 to Week 26. Change was calculated as: Average value of Weeks 15 to 26 - Average value of Baseline (Day -28 to Day -1).	Baseline to Week 15 through Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Average Morning ItchRO (Obs) Frequency Score Between Baseline and the Average of Week 15 Through Week 26	The ItchRO (Obs) scale measures frequency of pruritus. The score on ItchRO (Obs) scale ranged from 0 to 4, where 0=None observed or reported, 1= A little bit of the time, 2= Some of the time, 3= Most of the time, 4= Almost all of the time/constantly, I don't know) to describe their pruritus condition. 'I don't know' was categorized as missing data. A higher score indicated more severe pruritus. Baseline average morning ItchRO (Obs) frequency scores were calculated as the sum of the morning frequency scores divided by the number of morning severity scores for the 4-week (28 days) time periods. (i.e., Day -28 to Day -1). Average morning ItchRO (Obs) frequency scores of Week 15 through Week 26 were calculated as the sum of the morning frequency scores divided by the number of mornings frequency scores from Week 15 to Week 26. Change was calculated as: Average value of Weeks 15 to 26 - Average value of Baseline (Day -28 to Day -1).	Baseline to Week 15 through Week 26
Change From Baseline in Total Serum Bile Acid (sBA) Levels to Week 26	Change from baseline was calculated as: Post-baseline observed value - Baseline (before first dosing) observed value. Change from baseline in total sBA levels to Week 26 was reported.	Baseline to Week 26
Change in the ItchRO (Obs) Weekly Average Severity Between Baseline and the Average of Week 15 Through Week 26	ItchRO (Obs) scale measures severity of pruritus, score 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 was calculated based on daily maximum severity scores from both morning and evening. Average baseline morning and evening ItchRO (Obs) scores were calculated as sum of morning or evening scores divided by number of morning or evening scores for 4-week (28 days) time periods (i.e., Day -28 to Day -1). Average morning and evening ItchRO (Obs) scores Week 15 to Week 26 were calculated as sum of morning or evening scores divided by number of morning or evening scores from Week 15 to Week 26. Change was calculated as: Average value of Weeks 15 to 26 - Average value of Baseline (Day -28 to Day -1).	Baseline to Week 15 through Week 26
Percentage of Participants (Responders) Who Experienced an sBA Control From Baseline Through Week 26	Responders to sBA control were defined as participants who achieved a decrease to less than (<) 102 mcmol/L, a decrease of greater than (>) 75 percentage (%), or normalization at any timepoint from baseline through Week 26.	Baseline through Week 26

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 10, 2023
• Primary Completion (Actual): September 4, 2023
• Study Completion (Actual): July 22, 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 28, 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: Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Cholestasis, progressive familial intrahepatic 1
• Other Study ID Numbers: TAK-625-3002; jRCT2031220356 (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