Phase 2
N=68
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
Primary Biliary Cholangitis
Bottom Line
View on ClinicalTrials.gov: NCT03394924 ↗Enrolled (actual)
68
Serious AEs
4.4%
Results posted
May 2021
Primary outcome: Primary: Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline — 45.2; 46.4; 11.1 percentage of participants — p=0.106
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- EDP-305 1 mg (Drug); EDP-305 2.5 mg (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Enanta Pharmaceuticals, Inc
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline |
45.2; 46.4; 11.1 | 0.106 |
| SECONDARY Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period |
71.0; 89.3; 88.9 | — |
| SECONDARY Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period |
3.2; 7.1; 0 | — |
| SECONDARY Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period |
3.2; 17.9; 0 | — |
| SECONDARY Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin |
-0.04; -0.31; -0.50; -0.55; -0.51; 0.13 | 0.616 |
| SECONDARY Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) |
-17.35; -13.14; 8.20; -12.08; -11.51; 9.33 | 0.001 sig |
| SECONDARY Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Enhanced Liver Fibrosis (ELF) Panel and N-terminal Type III Collagen Propeptide (PRO C3) |
1.17; -1.16; 27.83; -0.08; -0.77; 3.01 | 0.148 |
| SECONDARY Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score |
-0.16; -0.12; 0.22 | 0.000 sig |
| SECONDARY Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score |
-0.14; -0.05; 0.21 | 0.026 sig |
| SECONDARY Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels |
16.28; 41.25; 9.47; -0.57; -2.69; 0.41 | 0.757 |
| SECONDARY Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels |
0.73; -2.10; 0.39; NA; NA; NA | 0.841 |
| SECONDARY Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels |
-0.14; -0.18; -0.15; -0.02; -0.00; 0.02 | 0.944 |
| SECONDARY Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) |
-0.13; 0.01; 0.05; -0.47; -0.46; 0.17 | 0.176 |
| SECONDARY Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale |
0.01; 0.41; -0.24; 0.00; 0.65; -0.53 | 0.378 |
| SECONDARY Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching |
0.55; 13.64; -11.93 | 0.16 |
| SECONDARY Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment |
-0.21; -1.46; -0.06; 0.18; 1.74; -1.73 | 0.908 |
| SECONDARY Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites |
15.4; 27.9; 10.8; 50.4; 0.5; 0.6 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites |
6.00; 6.02; 7.01; 6.01; 2.00; 6.00 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EDP-305 and Its Metabolites |
85.50; 95.30; 67.60; 316.20; 2.30; 2.00 | — |
| SECONDARY Percentage Change From Baseline to Week 12 in Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA) Concentrations |
28.10; 46.90; 39.83; -18.066; -61.960; 39.839 | 0.971 |
| SECONDARY Percentage Change From Baseline to Week 12 in AUC0-8 and AUC2-8 of Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA) |
24.9; 25.0; -25.9; 7.8; 18.9; -25.3 | 0.611 |
Summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis
Eligibility Criteria
Inclusion Criteria
- An informed consent document signed and dated by the subject.
- Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
- Male or female with a diagnosis of PBC by at least two of the following criteria:
- History of ALP above ULN for at least six months
- Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies)
- For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness ULN but 5 x ULN
- ALT >5 x ULN
- Patients with Gilbert's syndrome will not be allowed due to interpretability of bilirubin levels
- Total white blood cells (WBC) 1.2
- Serum creatinine >2 mg/dL or creatinine clearance 2 mg/dL (178 μmol/L)
- Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
- Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)
- Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least 3 months prior to Screening are allowed. No dose modification during the study will be allowed.
- Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive weeks in duration within 1 year prior to Screening.
Data sourced from ClinicalTrials.gov (NCT03394924). 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.