A Study of TAK-625 for the Treatment of Progressive Famil... | NCT05543187

NCT05543187

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
jRCT2031220356	Registry Identifier	jRCT

Status Module

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
TAK-625	Drug	TAK-625 orally, twice daily (BID)	TAK-625, Primary cohort TAK-625, Supplemental cohort

Outcomes Module

Primary Outcomes

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 Outcomes

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).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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:
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.
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.
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:

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.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Tsukuba Hospital		Tsukuba	Ibaraki		Japan
Yokohamashi Tobu Hospital

Label	URL
To obtain more information on the study, click here/on this link	View source

Arm/Group Information

ID	Title	Description
FG000	Primary Cohort: TAK-625	Participants diagnosed with PFIC2 due to ABCB11 mutation that predicted residual BSEP function received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 micrograms per kilograms (mcg/kg), 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.
FG001	Supplemental Cohort: TAK-625	Participants diagnosed with other PFIC subtypes or post-surgical received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 mcg/kg, 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Primary Cohort: TAK-625	Participants diagnosed with PFIC2 due to ABCB11 mutation that predicted residual BSEP function received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 mcg/kg, 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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).

ITT included all participants who received at least one dose of study drug. As per-planned analysis, the cohort-wise (primary and supplemental) data were analyzed, collected, and reported in this study.

Posted

Mean

95% Confidence Interval

score on a scale

Baseline to Week 15 through Week 26

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Primary Cohort: TAK-625	Participants diagnosed with PFIC2 due to ABCB11 mutation that predicted residual BSEP function received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 mcg/kg, 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 8, 2022	Aug 29, 2024	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Sep 5, 2025	Jan 12, 2026	SAP_002.pdf

OG000	Primary Cohort: TAK-625	Participants diagnosed with PFIC2 due to ABCB11 mutation that predicted residual BSEP function received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 mcg/kg, 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.
OG001	Supplemental Cohort: TAK-625	Participants diagnosed with other PFIC subtypes or post-surgical received TAK-625 orally, BID. In dose escalation period, dose was increased weekly, 150 mcg/kg, 300 mcg/kg, 450 mcg/kg, and 600 mcg/kg for up to 4 weeks (Weeks 1 to 4) or extended to 6 weeks depending on the safety or tolerability concerns. After the dose escalation period, each participant continued dosing with TAK-625 600 mcg/kg, orally, BID dose level in the stable dosing period, a follow-up dosing period after Week 48, and a safety follow-up period.