Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.
Up to 50 sites in the following countries will take part in this study:
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A4250 low dose | Experimental | Capsules for oral administration (40 ug/kg) once daily for 24 weeks |
|
| A4250 high dose | Experimental | Capsules for oral administration (120 ug/kg) once daily for 24 weeks |
|
| Placebo | Placebo Comparator | Capsules for oral administration (to match active) once daily for 24 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| A4250 (odevixibat) | Drug | A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in fasting s-BA from baseline to the end of treatment or reached <=70 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal. | From Baseline (Day 1) up to Week 24 |
| Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. | From Baseline (Day 1) up to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Blood samples for analysis of s-BA were drawn at all visits. Participants were to fast (water intake only was permissible) for at least 4 hours prior to the collection of samples. Exceptions could be made for infants <12 months of age if they were unable to fast for the full 4 hours. Baseline was the average of the last 2 non-missing values of fasting s-BA concentration prior to the first dose of study treatment. |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein
Participant with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:
Participant with past medical history or ongoing chronic diarrhea
Any participant with suspected or confirmed cancers except for basal cell carcinoma
Participant with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m^2
Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period
Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization
Decompensated liver disease
Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC
Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| University of California, San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36066745 | Derived | Gwaltney C, Ivanescu C, Karlsson L, Warholic N, Kjems L, Horn P. Validation of the PRUCISION Instruments in Pediatric Patients with Progressive Familial Intrahepatic Cholestasis. Adv Ther. 2022 Nov;39(11):5105-5125. doi: 10.1007/s12325-022-02262-7. Epub 2022 Sep 6. | |
| 35780807 | Derived | Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz O, Fischler B, Gonzales E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Ozen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P. Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):830-842. doi: 10.1016/S2468-1253(22)00093-0. Epub 2022 Jul 1. |
Not provided
Not provided
The study included up to an 8-week screening period, a 24-week treatment period, and a 4-week follow-up period. A total of 62 participants were enrolled in the study.
This Phase 3, double-blind, placebo-controlled study was conducted in children with progressive familial intrahepatic cholestasis (PFIC) at 33 study centers in 12 countries between 16 May 2018 and 28 July 2020.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to active drug (A4250). |
| FG001 | A4250 Low Dose | Capsules for oral administration [40 microgram per kilogram (mcg/kg)] once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 24, 2019 | Jul 12, 2021 |
Not provided
Not provided
Double-Blind, Randomized, Placebo-Controlled
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo identical in appearance to active drug (A4250). |
|
| Baseline (Day 1) and Weeks 12 and 24 |
| Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Blood samples were collected to determine the ALT concentration. Baseline was the last available assessment before the first dose of study treatment. | Baseline (Day 1) and Weeks 12 and 24 |
| Change From Baseline in Growth Parameters at Weeks 12 and 24 | The change in the growth parameters was assessed using linear growth deficit [height (centimeter), weight (kilogram) and body mass index (BMI) (kg/meter square)] compared to standard growth curve (Z-score) calculated by using the software or methods from the centers for disease control (CDC) website for participants with age >=2 years old and from the world health organization website for participants with age <2 years old. Participants whose accurate age was not available, Z-score was not calculated. A Z-score indicated how many standard deviation's (SD) a participant's measurement (like height, weight and BMI), was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below average a measurement was. Baseline was the last available assessment before the first dose of study treatment. | Baseline (Day 1) and Weeks 12 and 24 |
| Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | The responder for pruritus scores was defined as a participant who achieved at least a 1-point reduction in the ObsRO pruritus score. Percentages are rounded to hundredth decimal. | Weeks 12 and 24 |
| Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | The sleep disturbance were recorded twice daily via the electronic diary (eDiary). Participants and/or caregivers completed the eDiary every day in the morning and in the evening. The morning diary was completed shortly after the participant woke up and was used to record nighttime itching and scratching severity, aspects of sleep disturbance, and tiredness upon waking (AM scores). The evening/bedtime diary was completed just before the participant went to bed and recorded participant's itching and scratching severity, and tiredness during the day (PM scores). Both morning and bedtime diaries included Albireo ObsRO and PRO items. Baseline was the average of 14-day scores before the first dose of study treatment. | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | The ObsRO and electronic diary (eDiary) PRO scale called PRUCISION was used to assess pruritus and sleep outcomes. Participants and/or caregivers completed the eDiary every day in the morning (AM scores) and in the evening (PM scores). Specifically, for difficulty falling or staying asleep, the following 2 respective questions were asked in the Morning Daily eDiary: 1) How hard was it to fall asleep last night because of your itching. and 2) How hard was it to stay asleep last night because of your itching. The PRO was a 5-point scale, and scores ranged from 0 (no itching) to 28 (the worst itching), where higher scores indicated a greater amount of itching, sleep disturbance, and tiredness. No subscales were used. Change in sleep parameters measured with the Albireo PRO and ObsRO instruments by each 4-week interval over the 24-week treatment period was assessed. Baseline was the average of 14-day scores before the first dose of study treatment. | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | From Baseline (Day 1) up to Week 24 |
| Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo PRO instrument, only participants >=8 years of age completed the Albireo PRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | From Baseline (Day 1) up to Week 24 |
| Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | The number of participants underwent biliary diversion surgery and liver transplantation was determined. | From Baseline (Day 1) up to Week 24 |
| Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO and PRO instruments. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. | From Baseline (Day 1) up to Week 24 |
| San Francisco |
| California |
| 94143 |
| United States |
| Children's Hospital Colorado | Denver | Colorado | 80045 | United States |
| Emory University School of Medicine | Atlanta | Georgia | 30329 | United States |
| Johns Hopkins School of Medicine | Baltimore | Maryland | 21287 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Columbia University Medical Center - Presbyterian Hospital Building | New York | New York | 10032 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| Baylor College of Medicine - Texas Children's Liver Center | Houston | Texas | 77030 | United States |
| The Royal Children's Hospital | Melbourne | Australia |
| UZ Leuven | Leuven | Belgium |
| Cliniques Universitaires Saint-Luc | Woluwe-Saint-Lambert | Belgium |
| The Hospital for Sick Children | Toronto | Canada |
| British Columbia Children's Hospital | Vancouver | Canada |
| University and Pediatric Hospital of Lyon | Bron | France |
| Universite Paris SUD - Hopitaux Universitaires Paris-Sud - Hopital Bicetre | Le Kremlin-Bicêtre | France |
| Hospital de la Timone | Marseille | France |
| Hospital Necker-Enfants maladies | Paris | France |
| Uniklinikum Essen- Kinderklinik II | Essen | Germany |
| Medizinische Hochschule Hannover | Hanover | Germany |
| Kinderklinik Tübingen, Universitätsklinikum Tübingen | Tübingen | Germany |
| Rambam Medical Centre | Haifa | Israel |
| Shaare-Zedek Mc | Jerusalem | Israel |
| Schneider Children's Medical Center Of Israel | Petah Tikva | Israel |
| Azienda Ospedaliera Papa Giovanni XXIII | Bergamo | Italy |
| University Hospital Of Padova | Padova | Italy |
| Ospedale Regina Margherita | Torino | Italy |
| University Medical Center Groningen | Groningen | Netherlands |
| Universitair Medisch Centrum (UMC) Utrecht | Utrecht | Netherlands |
| Instytut Pomnik - Centrum Zdrowia Dziecka | Warsaw | Poland |
| King Faisal Specialist Hospital & Research Centre | Riyadh | 11211 | Saudi Arabia |
| Hospital Universitari Vall d'Hebron | Barcelona | Spain |
| Hospital Universitario La Paz | Madrid | Spain |
| Astrid Lindgren Children's Hospital, Karolinska University Hospital | Solna | Sweden |
| Gazi University | Ankara | Turkey (Türkiye) |
| Hacettepe University Faculty of Medicine | Ankara | Turkey (Türkiye) |
| Akdeniz University | Antalya | Turkey (Türkiye) |
| Istanbul University Medical Faculty | Istanbul | Turkey (Türkiye) |
| Inonu University Medical Faculty | Malatya | Turkey (Türkiye) |
| Birmingham Women's and Children's NHS Foundation Trust | Birmingham | United Kingdom |
| Leeds General Infirmary | Leeds | United Kingdom |
| Institute of Liver Studies - Kings College Hospital | London | United Kingdom |
| FG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
| Received Treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to active drug (A4250). |
| BG001 | A4250 Low Dose | Capsules for oral administration (40 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
| BG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants | No |
| |||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants | No |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
| |||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
| |||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Type of PFIC | PFIC Type 1: Familial intrahepatic cholestasis-1 (FIC1) protein deficiency, PFIC Type 2: Bile salt export pump (BSEP) deficiency. | Count of Participants | Participants | No |
|
| 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 | Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in fasting s-BA from baseline to the end of treatment or reached <=70 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal. | The FAS included all randomized participants who received at least 1 dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | From Baseline (Day 1) up to Week 24 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. | The FAS included all randomized participants who received at least 1 dose of study treatment. | Posted | Mean | Standard Error | percentage of assessments | From Baseline (Day 1) up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Blood samples for analysis of s-BA were drawn at all visits. Participants were to fast (water intake only was permissible) for at least 4 hours prior to the collection of samples. Exceptions could be made for infants <12 months of age if they were unable to fast for the full 4 hours. Baseline was the average of the last 2 non-missing values of fasting s-BA concentration prior to the first dose of study treatment. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported. | Posted | Mean | Standard Error | mcmol/L | Baseline (Day 1) and Weeks 12 and 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Blood samples were collected to determine the ALT concentration. Baseline was the last available assessment before the first dose of study treatment. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported. | Posted | Mean | Standard Error | units/L | Baseline (Day 1) and Weeks 12 and 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Growth Parameters at Weeks 12 and 24 | The change in the growth parameters was assessed using linear growth deficit [height (centimeter), weight (kilogram) and body mass index (BMI) (kg/meter square)] compared to standard growth curve (Z-score) calculated by using the software or methods from the centers for disease control (CDC) website for participants with age >=2 years old and from the world health organization website for participants with age <2 years old. Participants whose accurate age was not available, Z-score was not calculated. A Z-score indicated how many standard deviation's (SD) a participant's measurement (like height, weight and BMI), was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below average a measurement was. Baseline was the last available assessment before the first dose of study treatment. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported. | Posted | Mean | Standard Error | z-score | Baseline (Day 1) and Weeks 12 and 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | The responder for pruritus scores was defined as a participant who achieved at least a 1-point reduction in the ObsRO pruritus score. Percentages are rounded to hundredth decimal. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported. | Posted | Number | 95% Confidence Interval | percentage of participants | Weeks 12 and 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | The sleep disturbance were recorded twice daily via the electronic diary (eDiary). Participants and/or caregivers completed the eDiary every day in the morning and in the evening. The morning diary was completed shortly after the participant woke up and was used to record nighttime itching and scratching severity, aspects of sleep disturbance, and tiredness upon waking (AM scores). The evening/bedtime diary was completed just before the participant went to bed and recorded participant's itching and scratching severity, and tiredness during the day (PM scores). Both morning and bedtime diaries included Albireo ObsRO and PRO items. Baseline was the average of 14-day scores before the first dose of study treatment. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported. | Posted | Mean | Standard Error | percentage of days | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | The ObsRO and electronic diary (eDiary) PRO scale called PRUCISION was used to assess pruritus and sleep outcomes. Participants and/or caregivers completed the eDiary every day in the morning (AM scores) and in the evening (PM scores). Specifically, for difficulty falling or staying asleep, the following 2 respective questions were asked in the Morning Daily eDiary: 1) How hard was it to fall asleep last night because of your itching. and 2) How hard was it to stay asleep last night because of your itching. The PRO was a 5-point scale, and scores ranged from 0 (no itching) to 28 (the worst itching), where higher scores indicated a greater amount of itching, sleep disturbance, and tiredness. No subscales were used. Change in sleep parameters measured with the Albireo PRO and ObsRO instruments by each 4-week interval over the 24-week treatment period was assessed. Baseline was the average of 14-day scores before the first dose of study treatment. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported. | Posted | Mean | Standard Error | scores on a scale | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | The FAS included all randomized participants who received at least 1 dose of study treatment. | Posted | Mean | Standard Error | percentage of assessments | From Baseline (Day 1) up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo PRO instrument, only participants >=8 years of age completed the Albireo PRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | The FAS included all randomized participants who received at least 1 dose of study treatment. | Posted | Mean | Standard Error | percentage of assessments | From Baseline (Day 1) up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported. | Posted | Mean | Standard Error | percentage of assessments | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | The number of participants underwent biliary diversion surgery and liver transplantation was determined. | The FAS included all randomized participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | No | From Baseline (Day 1) up to Week 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | A positive pruritus assessment was defined as a scratching score of <=1 or at least 1 point drop from baseline based on the Albireo ObsRO and PRO instruments. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100. | The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected for specific instrument are reported. | Posted | Count of Participants | Participants | No | From Baseline (Day 1) up to Week 24 |
|
All serious and non-serious adverse events (AEs) were collected once the caregiver/participant had signed the informed consent form (ICF) and until the post-treatment follow-up (Visit 10) or 28 days after the last dose of study treatment, approximately 28 weeks
Treatment emergent adverse events were defined as any AE that occurred after first dose or AE occurred before first dose but worsened in severity on or after first dose. Treatment emergent serious adverse events and treatment emergent non-serious AEs are reported here.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to active drug (A4250). | 0 | 20 | 5 | 20 | 17 | 20 |
| EG001 | A4250 Low Dose | Capsules for oral administration (40 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | 0 | 23 | 0 | 23 | 19 | 23 |
| EG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | 0 | 19 | 3 | 19 | 16 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis adenovirus | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| H1N1 influenza | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Auricular haematoma | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Weight gain poor | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Splenomegaly | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Otorrhoea | Ear and labyrinth disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Eye discharge | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Adenovirus infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| H1N1 influenza | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Klebsiella infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Post procedural infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral diarrhoea | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral rash | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Auricular haematoma | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Scar | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Blood creatinine decreased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Liver palpable | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Platelet count increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Product residue present | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vitamin D decreased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vitamin E increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vitamin A deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Vitamin E deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Neck mass | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Selective eating disorder | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Cystitis haemorrhagic | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Genital rash | Reproductive system and breast disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Rash vesicular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Cardiac ablation | Surgical and medical procedures | MedDRA 23.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Sinusitis bacterial | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Skin candida | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
Albireo will retain the ownership of all data. All proposed publications based on this study must be subject to the sponsor's approval requirements.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick Horn, MD, PhD | Albireo AB | +1 (857) 378- 2035 | medinfo@albireopharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 25, 2020 | Jul 9, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D002779 | Cholestasis |
| ID | Term |
|---|---|
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000713258 | odevixibat |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| 6 to 12 years |
|
| 13 to 18 years |
|
| Male |
|
| Black or African American |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Native Hawaiian or Other Pacific Islander |
|
| Other |
|
| Not Hispanic or Latino |
|
| United Kingdom |
|
| Saudi Arabia |
|
| Canada |
|
| Netherlands |
|
| Turkey |
|
| Poland |
|
| Italy |
|
| Israel |
|
| France |
|
| Australia |
|
| Germany |
|
| Type 2 |
|
| Analysis was based on the Cochran Mantel Haenszel test adjusting PFIC type. A pooled analysis for the closed testing procedure was applied to control multiplicity. The 1-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses. 1-sided adjusted p-value was reported. | Cochran-Mantel-Haenszel | 0.0174 | percentage difference | 0.211 | 2-Sided | 95 | 0.021 | 0.4557 | Superiority |
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
| A4250 Low Dose |
Capsules for oral administration (40 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
| OG002 | A4250 High Dose | Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
| A4250 High Dose |
Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
| OG002 |
| A4250 High Dose |
Capsules for oral administration (120 mcg/kg) once daily for 24 weeks. A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. |
|
|
| Participants |
|
|
Capsules for oral administration (120 mcg/kg) once daily for 24 weeks.
A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT.
|
|