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

JRCT ID: jRCT2051220098

Registered date:22/09/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Alagille Syndrome (ALGS)
• Date of first enrollment: 16/01/2023
• Target sample size: 7
• Study type: Interventional
• Intervention(s): 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.

Outcome(s)

Primary Outcome

1.Change of Fasting Serum Bile Acid (sBA) Levels from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of fasting sBA levels from Week 18 to Week 22 will be reported.

Secondary Outcome

1.Change of Fasting sBA Levels from Baseline to Week 18
Time Frame: From baseline to Week 18
Change of fasting sBA levels from baseline to Week 18 will be reported.

2.Change of Weekly Average Severity of Pruritus Measured by ItchRO (Obs) from baseline to Week 18
Time Frame: From baseline to Week 18
Change of weekly average severity of pruritus measured by ItchRO (Obs) from baseline to Week 18 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Caregivers will rate the severity of pruritus using 5 choices (0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe) to describe their pruritus condition. Weekly average severity is a score calculated from the sum of all daily scores, based on daily maximum of morning and evening severity scores, divided by the number of weeks the ItchRO was completed.

3.Change of Weekly Average Morning Severity of Pruritus Measured by ItchRO (Obs) from baseline to Week 18
Time Frame: From baseline to Week 18
Change of weekly average morning severity of pruritus measured by ItchRO (Obs) from baseline to Week 18 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Caregivers will rate the severity of pruritus using 5 choices (0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe) to describe their pruritus condition. Weekly average morning severity is a score calculated from the sum of all daily morning scores divided by the number of weeks the ItchRO was completed.

4.Change of Weekly Average Severity of Pruritus Measured by ItchRO (Obs) from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of weekly average severity of pruritus measured by ItchRO (Obs) from Week 18 to Week 22 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Caregivers will rate the severity of pruritus using 5 choices (0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe) to describe their pruritus condition. Weekly average severity is a score calculated from the sum of all daily scores, based on daily maximum of morning and evening severity scores, divided by the number of weeks the ItchRO was completed.

5.Change of Weekly Average Morning Severity of Pruritus Measured by ItchRO (Obs) from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of weekly average morning severity of pruritus measured by ItchRO (Obs) from Week 18 to Week 22 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Caregivers will rate the severity of pruritus using 5 choices (0=None observed or reported, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe) to describe their pruritus condition. Weekly average morning severity is a score calculated from the sum of all daily morning scores divided by the number of weeks the ItchRO was completed.

6.Change of Weekly Average Severity of Pruritus Measured by ItchRO (Pt) from baseline to Week 18
Time Frame: From baseline to Week 18
Change of weekly average severity of pruritus measured by ItchRO (Pt) from baseline to Week 18 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Participants will rate the severity of pruritus using 5 choices (0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy) to describe their pruritus condition. Weekly average severity is a score calculated from the sum of all daily scores, based on daily maximum of morning and evening severity scores, divided by the number of weeks the ItchRO was completed.

7.Change of Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) from baseline to Week 18
Time Frame: From baseline to Week 18
Change of weekly average morning severity of pruritus measured by ItchRO (Pt) from baseline to Week 18 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Participants will rate the severity of pruritus using 5 choices (0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy) to describe their pruritus condition. Weekly average morning severity is a score calculated from the sum of all daily morning scores divided by the number of weeks the ItchRO was completed.

8.Change of Alanine Aminotransferase (ALT) Levels from Baseline to Week 18
Time Frame: From baseline to Week 18
Change of ALT levels from baseline to Week 18 will be reported.

9.Change of Alkaline Phosphatase (ALP) Levels from Baseline to Week 18
Time Frame: From baseline to Week 18
Change of ALP levels from baseline to Week 18 will be reported.

10.Change of Bilirubin (Total and Direct) Levels from Baseline to Week 18
Time Frame: From baseline to Week 18
Change of bilirubin (total and direct) levels from baseline to Week 18 will be reported.

11.Change of Weekly Average Severity of Pruritus Measured by ItchRO (Pt) from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of weekly average severity of pruritus measured by ItchRO (Pt) from Week 18 to Week 22 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Participants will rate the severity of pruritus using 5 choices (0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy) to describe their pruritus condition. Weekly average severity is a score calculated from the sum of all daily scores, based on daily maximum of morning and evening severity scores, divided by the number of weeks the ItchRO was completed.

12.Change of Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of weekly average morning severity of pruritus measured by ItchRO (Pt) from Week 18 to Week 22 will be reported. Pruritus will be assessed using the Itch caregiver/patient reported outcome (Patient Reported Outcome; PRO) measure (ItchRO) twice a day (once in the morning and once in the evening). Participants will rate the severity of pruritus using 5 choices (0= Not felt itchy, 1= Felt a little bit itchy, 2= Felt pretty itchy, 3= Felt very itchy, 4= Felt very, very itchy) to describe their pruritus condition. Weekly average morning severity is a score calculated from the sum of all daily morning scores divided by the number of weeks the ItchRO was completed.

13.Change of Alanine Aminotransferase (ALT) Levels from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of ALT levels from Week 18 to Week 22 will be reported.

14.Change of Alkaline Phosphatase (ALP) Levels from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of ALP levels From Week 18 to Week 22 will be reported.

15.Change of Bilirubin (Total and Direct) Levels from Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change of bilirubin (total and direct) levels from Week 18 to Week 22 will be reported.

Key inclusion & exclusion criteria

• Age minimum: >= 1month old
• Age maximum: Not applicable
• Gender: Both

Include 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:
a)Total serum bile acid (sBA) >3^ upper limit of the normal range (ULN) for age.
b)Direct bilirubin (conjugated) >1 mg/dL.
c)Lipid soluble vitamin (LSV) deficiency otherwise unexplainable.
d)Gamma-glutamyl transferase (GGT) >3^ULN for age.
e)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.

Exclude 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.

Related Information

• Primary Sponsor: Shikamura Mitsuhiro
• Secondary ID(s): NCT05543174