Phase 3
N=62
This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
PFIC1 · PFIC2
Bottom Line
View on ClinicalTrials.gov: NCT03566238 ↗Enrolled (actual)
62
Serious AEs
12.9%
Results posted
Sep 2021
Primary outcome: 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 — 0; 43.5; 21.1 percentage of participants — p=0.0015
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- A4250 (odevixibat) (Drug); Placebo (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Albireo
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
0; 43.5; 21.1 | 0.0015 sig |
| 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 |
28.74; 58.31; 47.69 | 0.0019 sig |
| SECONDARY Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 |
7.44; -113.70; -106.44; 18.64; -145.03; -72.90 | — |
| SECONDARY Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 |
1.7; -25.9; -13.8; 3.7; -27.9; -25.3 | — |
| SECONDARY Change From Baseline in Growth Parameters at Weeks 12 and 24 |
-0.03; 0.01; -0.06; -0.16; 0.05; 0.00 | — |
| 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 |
5.0; 60.9; 42.1; 10.0; 52.2; 42.1 | — |
| SECONDARY Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period |
-15.79; -14.42; -12.97; -12.10; -26.22; -13.99 | — |
| SECONDARY Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period |
-0.46; -0.72; -0.59; -0.34; -1.40; -0.65 | — |
| 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 |
33.48; 51.40; 42.48; 31.96; 57.07; 53.95 | — |
| 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 |
64.29; 43.75; 38.93; 46.88; 52.68; 41.96 | — |
| 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 |
33.48; 51.40; 42.48; 31.96; 57.07; 53.95 | — |
| SECONDARY Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation |
0; 0; 0; 0; 0; 0 | — |
| 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 |
4; 17; 9; 3; 13; 10 | — |
Summary
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.
Eligibility Criteria
Key Inclusion Criteria
- A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
- Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2
- Participant must have elevated serum bile acid (s-BA) concentration
- Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
- Participant and/or legal guardian must sign informed consent (and assent) as appropriate.
- Participants will be expected to have a consistent caregiver(s) for the duration of the study
- Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study
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:
- Biliary atresia of any kind
- Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
- Suspected or proven liver cancer or metastasis to the liver on imaging studies
- Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis
- 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
Data sourced from ClinicalTrials.gov (NCT03566238). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.