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

NCT05543187 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: TAK-625-3002jRCT2031220356
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Progressive Familial Intrahepatic Cholestasis (PFIC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in the Average Morning ItchRO (Obs) Frequency Score Between Baseline and the Average of Week 15 Through Week 26

  Baseline to Week 15 through Week 26

• Change From Baseline in Total Serum Bile Acid (sBA) Levels to Week 26

  Baseline to Week 26

• Percentage of Participants (Responders) Who Experienced an sBA Control From Baseline Through Week 26

  Baseline through Week 26

• Change in the ItchRO (Obs) Weekly Average Severity Between Baseline and the Average of Week 15 Through Week 26

  Baseline to Week 15 through Week 26

Study Arms (2)

TAK-625, Primary cohort

EXPERIMENTAL

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, Supplemental cohort

EXPERIMENTAL

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

Interventions

TAK-625 DRUG

TAK-625 orally, twice daily (BID)

Also known as: Maralixibat chloride

TAK-625, Primary cohort; TAK-625, Supplemental cohort

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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.
• 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 \[Week 0/Visit 2\]).
• 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:
• 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.
• The participant has a PFIC phenotype without a known mutation or with another known mutation not described above.
• The PFIC participant has internal or external biliary diversion surgery history, and the internal or external biliary diversion surgery was reversed.
• The participant (whenever possible) and caregiver are able to be contacted by phone for scheduled remote visits (participant contacts \[phone calls\]).
• Both a caregiver and participant above the age of assent are capable of reading and understanding the questionnaires.

You may not qualify if:

• 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).
• The participant has a diagnosis of benign recurrent intrahepatic cholestasis indicated by a history of intermittent cholestasis with no disease progression.
• The participant has a current or recent history (\<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
• The participant has a previous history of surgical interruption of the enterohepatic circulation (applies to the primary cohort only).
• 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.
• The participant has a history of liver transplant or currently requires imminent liver transplant.
• 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).
• The participant has an alanine aminotransferase (ALT) or total serum bilirubin (TSB) level \>15\^ ULN at screening.
• The participant has other liver disease.
• 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.
• The participant has a possible malignant liver mass in imaging, including screening ultrasound.
• 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.
• The participant who has received sodium phenylbutyrate for less than 6 months at the initiation of screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (8)

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Location

Yokohamashi Tobu Hospital

Yokohama, Kanagawa, Japan

Location

Tsuyama Chuo Hospital

Tsuyama, Okayama-ken, Japan

Location

Osaka University Hospital

Suita, Osaka, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

Kyoto University Hospital

Kyoto, Japan

Location

Saitama Prefectural Children's Medical Center

Saitama, Japan

Location

Related Links

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

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: January 10, 2023
• Primary Completion: September 4, 2023
• Study Completion: July 22, 2025
• Last Updated: January 28, 2026
• Results First Posted: September 24, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (8)