An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-625 in the Treatment of Subjects with Alagille Syndrome
A Study of TAK-625 for the Treatment of Alagille Syndrome (ALGS)
Shikamura Mitsuhiro
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Not Recruiting
Jan. 16, 2023
Jan. 16, 2023
7
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
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.
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.
0age 1month old over
No limit
Both
Alagille Syndrome (ALGS)
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.
1. Change in Fasting Serum Bile Acid (sBA) Levels From Week 18 to Week 22
Time Frame: From Week 18 to Week 22
Change in fasting sBA levels from Week 18 to Week 22 was reported. Change was calculated as: observed value at Week 22- observed value at Week 18.
1. Change in Fasting sBA Levels From Baseline to Week 18
Time Frame: 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).
2. Change in Weekly Average Severity of Pruritus Measured by Itch Reported Outcome (ItchRO) (Observer Instrument [Obs]) From Baseline to Week 18
Time Frame: 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).
3. Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Obs) From Baseline to Week 18
Time Frame: 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).
4. Change in Weekly Average Severity of Pruritus Measured by ItchRO (Obs) From Week 18 to Week 22
Time Frame: 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).
5. Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Obs) From Week 18 to Week 22
Time Frame: 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).
6. Change in Weekly Average Severity of Pruritus Measured by ItchRO (Pt) From Baseline to Week 18
Time Frame: 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).
7. Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) From Baseline to Week 18
Time Frame: 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).
8. Change in Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels From Baseline to Week 18
Time Frame: 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).
9. Change in Bilirubin (Total and Direct) Levels From Baseline to Week 18
Time Frame: 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).
10. Change in Weekly Average Severity of Pruritus Measured by ItchRO (Pt) From Week 18 to Week 22
Time Frame: From Week 18 to 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).
11. Change in Weekly Average Morning Severity of Pruritus Measured by ItchRO (Pt) From Week 18 to Week 22
Time Frame: From Week 18 to 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).
12. Change in ALT and ALP Levels From Week 18 to 22
Time Frame: 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.
13. Change in Bilirubin (Total and Direct) Levels from Week 18 to 22
Time Frame: From Week 18 to 22
Change of 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.
Takeda Pharmaceutical Company Limited
Kindai University Nara Hospital Institutional Review Board
1248-1, Otodacho Ikoma, Nara
+81-743-77-0880
tiken-jimukyoku@med.kindai.ac.jp
Approval
Sept. 26, 2022
No
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).
