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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003876-38 | EudraCT Number |
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Enanta Pharmaceuticals, Inc. made the strategic decision to discontinue the ARGON-2 study to prioritize combination treatment approaches. This decision was not based on safety concerns.
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A randomized, double-blind study to assess the safety and efficacy of EDP-305 in subjects with liver-biopsy proven Non-Alcoholic Steatohepatitis (NASH)
The aim of this Phase 2b study aimed to evaluate safety and efficacy of the investigational novel FXR agonist, EDP-305, in a population of patients with liver biopsy proven NASH.
This Phase 2b study aimed to evaluate the safety and efficacy of two doses of EDP-305 compared to placebo for the treatment of NASH in subjects with liver biopsy proven NASH. As suggested in the FDA guidance, this late stage Phase 2 study explored the effect of EDP-305/placebo treatment on histological endpoints. The patient population selected for inclusion in the study was designed to represent the target population for treatment. Specifically, in patients with liver disease, there is a significant overlap of NASH and various metabolic conditions including obesity and T2DM. In order to be reflective of the NASH population, these patients were not excluded from participation in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EDP-305 1.5 mg | Experimental | Once a day orally for 72 weeks |
|
| EDP-305 2 mg | Experimental | Once a day orally for 72 weeks |
|
| Placebo | Placebo Comparator | Once a day orally for 72 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EDP-305 1.5 mg | Drug | Tablet |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Who Achieve ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis and/or Resolution of Steatohepatitis and no Worsening of Liver Fibrosis as Determined by Liver Biopsy | Proportion of participants who achieve ≥1 stage improvement in fibrosis without worsening of steatohepatitis and/or resolution of steatohepatitis and no worsening of liver fibrosis as determined by liver biopsy. | Week 72 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 5D-itch Scale From Baseline | 5D-itch scale, change from baseline at Week 12. Change from baseline for 5D-itch scale was analyzed using a restricted maximum likelihood-based mixed model repeated measures (MMRM) technique. The model included treatment, visit, treatment-by-visit interaction as fixed effects along with baseline NAS score and baseline score for 5D-itch scale as covariate. A multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. The total 5D score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus). |
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Inclusion Criteria:
Exclusion Criteria:
Laboratory Screening results as indicated below:
Pregnant or nursing females.
MELD: Model for End-stage Liver Disease score >12.
Clinical or laboratory evidence of known chronic liver disease such as alcoholic liver disease, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC).
History of acute liver complications due to gallstones (e.g., acute cholecystitis or acute biliary obstruction) unless the participant had a cholecytectomy (more than 3 months prior to screening).
History of liver transplant, or current placement on a liver transplant list.
Hepatorenal syndrome (type I or II).
Prior variceal hemorrhage, uncontrolled encephalopathy, liver cirrhosis Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 26 weeks of Screening and/or histological presence of liver cirrhosis.
Prior or planned ileal resection, or prior or planned bariatric surgery. [Note: Participants who had undergone gastric surgeries that did not affect drug absorption (e.g., gastric band or gastric sleeve procedures) were allowed if they were stable for at least 1 year prior to Screening. Gastrectomy or Roux-en-Y bypass was allowed if stable for at least 3 years prior to Screening.]
Participants with clinically or otherwise documented cardiovascular or cerebrovascular disease including clinically significant anomalies of rhythm or pattern of ECG, that in the judgement of the Principal Investigator (PI) could affect the safety of the participant or their ability to comply with the study requirements.
HbA1c ≥ 9.5% within 60 days prior to Day 1.
Use of a new antidiabetic regimen in the months prior to Screening including metformin, glucagon-like peptide (GLP) 1 agonists, sodium glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, or dipeptidyl peptidase 4 (DPP4) inhibitors, insulin or peroxisome proliferator-activated receptor (PPAR)γ agonists (e.g., pioglitazone or rosiglitazone). For pre-existing antidiabetic treatment, participants were to be on a stable dose of antidiabetic drugs: (1) for at least 8 weeks (for metformin and/or sulfonylureas), (2) 12 weeks (for SGLT2 or DPP4 inhibitors), or (3) 12 weeks (for GLP-1 receptor agonists and thiazolidinediones) prior to Screening with the intention to keep the regimen stable during the study.
Use of a new statin regimen or other lipid lowering agents from 12 weeks prior to Screening.
Use of a new fibrate regimen from 12 weeks prior to Screening.
Participants with contraindications to MRI imaging, or not being able to have the MRI performed.
Participant had received any investigational agent (including investigational vaccine) or biological product within 30 days or 5 times the half-life (whichever was longer) prior to the planned first dose of study drug.
Use of an experimental or approved treatment for NASH within 26 weeks of Screening.
Prior use of OCA within 26 weeks of Screening and/or concurrent treatment with OCA (or any other FXR agonists).
Use of systemic immunosuppressant (e.g., corticosteroids) for more than 4 weeks in duration within 1 year prior to Screening with the intention to continue during the study (chronic use of inhaled, topical, ophthalmological, nasal corticosteroids was allowed)
Use of any prohibited concomitant medications, including systemic CYP3A4 inhibitors and inducers, within 14 days prior to the first dose of study drug and for the duration of the study.
Clinically significant history of drug sensitivity or drug allergy, as determined by the PI.
Current or history of significant alcohol consumption defined as: >14 standard drinks per week and/or ≥4 standard drinks per occasion for males and >7 standard drinks per week and/or ≥3 standard drinks per occasion for females.
History of substance (including alcohol) abuse and in the judgement of the PI, the participant was not suitable for participation in the study.
Any other condition(s) that would compromise the safety of the participant or compromise the quality of the clinical study, as judged by the PI.
Use of medication for weight loss or appetite reduction (e.g., orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin, non-prescription supplements) at Screening.
History of malignancy of any organ system (other than localized and considered cured cutaneous basal or squamous cell carcinoma, or in situ cervical cancer), treated or untreated, within 5 years of Screening.
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| Name | Affiliation | Role |
|---|---|---|
| Enanta Pharmaceuticals, Inc | Enanta Pharmaceuticals, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Liver Health | Chandler | Arizona | 85224 | United States | ||
| The Institute of Liver Health |
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Screening assessments were conducted within 70 days prior to the first dose of study drug (i.e., Study Days -70 to -1). Screening assessments were performed and confirmed sequentially as follows: a) medical history and other noninvasive assessments, b) laboratory assessments, c) MRI-PDFF and MRE and, lastly, d) liver biopsy.
Male and female subjects with liver biopsy proven NASH between the ages of 18 and 75 years, inclusive, and with a NAS of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2) and fibrosis stage 2 or 3 using the NASH Clinical Research Network (CRN) Histologic Scoring System were eligible for inclusion. Subjects had to be negative for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV).
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| ID | Title | Description |
|---|---|---|
| FG000 | EDP-305 1.5 mg | Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet |
| FG001 | EDP-305 2 mg | Once a day orally for 72 weeks EDP-305 2 mg: Tablet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 21, 2021 | Oct 28, 2022 |
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| EDP-305 2 mg |
| Drug |
Tablet |
|
|
| Placebo | Drug | Tablet |
|
| Baseline, Week 12 |
| Proportion of Participants With Improvement of Fibrosis by at Least 1 Stage and/or Resolution of NASH Without Worsening of Either as Determined by Liver Biopsy | Description of endpoint is Proportion of participants with improvement of fibrosis by at least 1 stage and/or resolution of NASH without worsening of either as determined by liver biopsy. | Week 72 |
| Proportion of Participants With no Worsening of Fibrosis Combined With no Worsening of NASH as Determined by Liver Biopsy | Proportion of participants with no worsening of fibrosis combined with no worsening of NASH as determined by liver biopsy. | Week 72 |
| Proportion of Participants With Resolution of Fibrosis as Determined by Liver Biopsy | Proportion of participants with resolution of fibrosis as determined by liver biopsy at Week 72. | Week 72 |
| Proportion of Participants With Improvement in Each Histologic Feature of NASH by at Least 1 Point as Determined by Liver Biopsy | Proportion of participants with improvement in each histologic feature of NASH by at least 1 point as determined by liver biopsy at Week 72. | Week 72 |
| Proportion of Participants With Improvement of Fibrosis by ≥ 2 Stages by Liver Biopsy | Proportion of participants with improvement of fibrosis by ≥ 2 stages by liver biopsy. | Week 72 |
| Proportion of Participants With Improvement in NAS by at Least 2 Points With no Worsening of Fibrosis as Determined by Liver Biopsy | Proportion of participants with improvement in NAS by at least 2 points with no worsening of fibrosis as determined by liver biopsy at Week 72. | Week 72 |
| Proportion of Participants With Improvement of Fibrosis and Resolution of NASH as a Composite Endpoint as Defined by Both Endpoints Being Met in the Same Participant | Proportion of participants with improvement of fibrosis and resolution of NASH as a composite endpoint as defined by both endpoints being met in the same participant at week 72. | Baseline, Week 72 |
| Proportion of Participants With Resolution of NASH and no Worsening of Liver Fibrosis | Proportion of participants with resolution of NASH and no worsening of liver fibrosis at Week 72. | Week 72 |
| Proportion of Participants With Histological Progression to Cirrhosis as Determined by Liver Biopsy | Proportion of participants with histological progression to cirrhosis as determined by liver biopsy at Week 72. | Week 72 |
| Participants With TEAEs Leading to Discontinuation | Treatment emergent adverse events (TEAEs) were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug. TEAEs were regarded as leading to discontinuation if they led to discontinuation of the study drug. | Day 1 to Week 72 |
| Percentage Change of Fat in the Liver From Baseline | Percentage change of fat in the liver as assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF) from Baseline to Week 12. | Baseline, Week 12 |
| Change in Liver Stiffness From Baseline | Change in liver stiffness by magnetic resonance elastography (MRE) in kilopascal (kPa) from Baseline at Week 12. | Baseline, Week 12 |
| Change in Triglycerides From Baseline | Change in Triglycerides from Baseline at Week 12. | Baseline, Week 12 |
| Change in Adiponectin From Baseline | Change in adiponectin from Baseline at Week 12. | Baseline, Week 12 |
| Plasma Concentration of EDP-305 | Plasma concentration at second post dose (2-4 hours post dose) at Week 12. | 2-4 hours post dose at Week 12 |
| Change in VAS (Visual Analog Score) From Baseline | Change in VAS from Baseline at Week 12. Change from baseline was analyzed using a restricted maximum likelihood-based MMRM technique. Two separate scales were used to assess pruritus. An itch VAS was used to record the intensity of the pruritus by Furue (Furue et al., 2013). Scale referred to no pruritus (0 point) and the end of the scale to the most severe pruritus (10 points). If the VAS score was greater than zero (i.e. itch), a multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. It was used to assess five different dimensions of pruritus within the last two weeks. The five dimensions assessed were duration, degree, direction, disability, and distribution. The total 5D itch score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus). | Baseline, Week 12 |
| Change in Total Cholesterol From Baseline | Change in Total Cholesterol from Baseline to Week 12 versus placebo. | Baseline, Week 12 |
| Change in HDL From Baseline | Change in HDL from Baseline at week 12. | Baseline, Week 12 |
| Change in LDL From Baseline | Change in LDL From Baseline to Week 12. | Baseline, Week 12 |
| Glendale |
| Arizona |
| 85306 |
| United States |
| Dignity Health DBA St. Joseph's Hospital and Medical Center | Phoenix | Arizona | 85013 | United States |
| Del Sol Research Management LLC | Tucson | Arizona | 85710 | United States |
| Rajeev Krishan, MD, Inc | Bakersfield | California | 93309 | United States |
| eStudy Site | Chula Vista | California | 91911 | United States |
| Southern California Research Center | Coronado | California | 92118 | United States |
| St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare | Fullerton | California | 92835 | United States |
| National Institute of Clinical Research, Inc | Garden Grove | California | 92844 | United States |
| eStudySite - La Mesa | La Mesa | California | 91942 | United States |
| Om Research LLC | Lancaster | California | 93534 | United States |
| Keck Medical Center Of USC | Los Angeles | California | 90033 | United States |
| Inland Empire Liver Foundation | Rialto | California | 92377 | United States |
| UC Davis Medical Center | Sacramento | California | 95817 | United States |
| Southern California Gastrointestinal and Liver Centers | San Clemente | California | 92673 | United States |
| Precision Research Institute, Llc | San Diego | California | 92114 | United States |
| Paradigm Clinical Research Institute | Torrance | California | 90502 | United States |
| Universal Axon Clinical Research | Doral | Florida | 33166 | United States |
| Fleming Island Center for Clinical Research | Fleming Island | Florida | 32003 | United States |
| Universal Axon- Homestead, LLC | Homestead | Florida | 33030 | United States |
| Nature Coast Clinical Research | Inverness | Florida | 34452 | United States |
| Westside Center for Clinical Research | Jacksonville | Florida | 32205 | United States |
| Jacksonville Center for Endoscopy - Southside ; Borland Groover Clinic | Jacksonville | Florida | 32226 | United States |
| Encore Borland Groover Clinical Research | Jacksonville | Florida | 32256 | United States |
| Meridien Research | Lakeland | Florida | 33803 | United States |
| Meridien Research | Maitland | Florida | 32751 | United States |
| Research Associates of South Florida | Miami | Florida | 33134 | United States |
| University of Miami, Miller School of Medicine-Don Soffer Clinical Research Center | Miami | Florida | 33136 | United States |
| Well Pharma Medical Research, Corp. | Miami | Florida | 33173 | United States |
| Med Research Of Florida, LLC | Miami | Florida | 33186 | United States |
| San Marcus Research Clinic, Inc. | Miami Lakes | Florida | 33014 | United States |
| Ocala GI Research | Ocala | Florida | 34471 | United States |
| IMIC, Inc. | Palmetto Bay | Florida | 33157 | United States |
| Meridien Research | St. Petersburg | Florida | 33709 | United States |
| Guardian Angel Research | Tampa | Florida | 33614 | United States |
| Agile Clinical Research Trials, LLC | Atlanta | Georgia | 30328 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Rush University Medical Center - University Cardiovascular Surgeons | Chicago | Illinois | 60612-3852 | United States |
| Digestive Research Alliance of Michiana | South Bend | Indiana | 46635 | United States |
| University Of Iowa Hospital & Clinics | Iowa City | Iowa | 52242 | United States |
| Ochsner Health System | New Orleans | Louisiana | 70115-6969 | United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| Mercy Medical Center | Baltimore | Maryland | 21202 | United States |
| Digestive Disease Associates, PA | Catonsville | Maryland | 21228 | United States |
| Mid-Atlantic GI Research | Greenbelt | Maryland | 20770 | United States |
| Henry Ford Health Hospital | Detroit | Michigan | 48202 | United States |
| Southern Therapy and Advanced Research LLC GI Associates and Endoscopy Center | Jackson | Mississippi | 39216 | United States |
| St. Louis Univ. School Of Medicine | St Louis | Missouri | 63104 | United States |
| AGA Clinical Research Associates, LLC | Egg Harbor | New Jersey | 08234 | United States |
| Intercity Gastroenterology | Fresh Meadows | New York | 11366 | United States |
| New York University Medical Centre | New York | New York | 10016 | United States |
| University of Rochester Medical Center School of Medicine and Dentistry | Rochester | New York | 14642 | United States |
| Northeast GI Research Division | Concord | North Carolina | 28027 | United States |
| Carolinas HealthCare System Digestive - Huntersville | Huntersville | North Carolina | 28078 | United States |
| Lucas Research | Morehead City | North Carolina | 28557 | United States |
| Cleveland Clinic - Taussig Cancer Institute | Cleveland | Ohio | 44195 | United States |
| University of Pittsburgh Medical Center - Center for Liver Diseases | Pittsburgh | Pennsylvania | 15213 | United States |
| Digestive Health Research, LLC | Hermitage | Tennessee | 37076 | United States |
| Digestive Health Research | Lebanon | Tennessee | 37090 | United States |
| Quality Medical Research | Nashville | Tennessee | 37211 | United States |
| Texas Clinical Research Institute | Arlington | Texas | 76012 | United States |
| Texas Diabetes & Endocrinology | Austin | Texas | 78749 | United States |
| Crescent Health Clinical | DeSoto | Texas | 75115 | United States |
| DHAT Research Institute | Garland | Texas | 75044 | United States |
| American Research Corporation at The Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| Clinical Trials of Texas, Inc. | San Antonio | Texas | 78229 | United States |
| Bon Secours St. Mary's Hospital of Richmond, Inc | Newport News | Virginia | 23602 | United States |
| Liver Institute Northwest | Seattle | Washington | 98105 | United States |
| CINME | Buenos Aires | Buenos Aires F.D. | C1056AB | Argentina |
| University of Calgary | Calgary | Alberta | T2N 4Z6 | Canada |
| Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt | Frankfurt am Main | Hesse | 60590 | Germany |
| Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Latin Clinical Trial Center | San Juan | 00909 | Puerto Rico |
| MediNova West London Quality Research Site | Wokingham | Berkshire | RG40 1XS | United Kingdom |
| MeDiNova East London Quality Research Site | Romford | Essex | RM1 3PJ | United Kingdom |
| King's College Hospital - King's College Hospital NHS Foundation Trust | London | Greater London | SE5 9RS | United Kingdom |
| MeDiNova South London Quality Research Site | Sidcup | Kent | DA14 6LT | United Kingdom |
| MeDiNova Northampton Dedicated research site | Corby | Northamptonshire | NN18 9EZ | United Kingdom |
| MeDiNova Warwickshire Quality Research Site | Kenilworth | Warwickshire | CV81JD | United Kingdom |
| MeDiNova Yorkshire Quality Research Site | Shipley | Yorkshire | BD18 3SA | United Kingdom |
| MeDiNova North London Quality Research Site | Middlesex | HA6 2RN | United Kingdom |
| FG002 | Placebo | Once a day orally for 72 weeks Placebo: Tablet |
| COMPLETED |
|
| NOT COMPLETED |
|
|
NOTE: In the EDP-305 2mg arm 1 participant was randomized but not treated.
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| ID | Title | Description |
|---|---|---|
| BG000 | EDP-305 1.5 mg | Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet |
| BG001 | EDP-305 2 mg | Once a day orally for 72 weeks EDP-305 2 mg: Tablet |
| BG002 | Placebo | Once a day orally for 72 weeks Placebo: Tablet |
| 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 |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| 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 | Proportion of Participants Who Achieve ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis and/or Resolution of Steatohepatitis and no Worsening of Liver Fibrosis as Determined by Liver Biopsy | Proportion of participants who achieve ≥1 stage improvement in fibrosis without worsening of steatohepatitis and/or resolution of steatohepatitis and no worsening of liver fibrosis as determined by liver biopsy. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
| |||||||||||||||||||||||||
| Secondary | Change in 5D-itch Scale From Baseline | 5D-itch scale, change from baseline at Week 12. Change from baseline for 5D-itch scale was analyzed using a restricted maximum likelihood-based mixed model repeated measures (MMRM) technique. The model included treatment, visit, treatment-by-visit interaction as fixed effects along with baseline NAS score and baseline score for 5D-itch scale as covariate. A multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. The total 5D score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus). | ITT population: Intent-to-treat population (ITT) defined as all participants who randomized to treatment. Participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 7, n = 6 and n = 7 for EDP-305 1.5, 2mg and Placebo groups, respectively, presented as LS Mean (95% CI). | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Week 12 |
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| Secondary | Proportion of Participants With Improvement of Fibrosis by at Least 1 Stage and/or Resolution of NASH Without Worsening of Either as Determined by Liver Biopsy | Description of endpoint is Proportion of participants with improvement of fibrosis by at least 1 stage and/or resolution of NASH without worsening of either as determined by liver biopsy. | Due to study termination, the biopsy at Week 72 was not performed for any participants. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With no Worsening of Fibrosis Combined With no Worsening of NASH as Determined by Liver Biopsy | Proportion of participants with no worsening of fibrosis combined with no worsening of NASH as determined by liver biopsy. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With Resolution of Fibrosis as Determined by Liver Biopsy | Proportion of participants with resolution of fibrosis as determined by liver biopsy at Week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With Improvement in Each Histologic Feature of NASH by at Least 1 Point as Determined by Liver Biopsy | Proportion of participants with improvement in each histologic feature of NASH by at least 1 point as determined by liver biopsy at Week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With Improvement of Fibrosis by ≥ 2 Stages by Liver Biopsy | Proportion of participants with improvement of fibrosis by ≥ 2 stages by liver biopsy. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
| |||||||||||||||||||||||||
| Secondary | Proportion of Participants With Improvement in NAS by at Least 2 Points With no Worsening of Fibrosis as Determined by Liver Biopsy | Proportion of participants with improvement in NAS by at least 2 points with no worsening of fibrosis as determined by liver biopsy at Week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With Improvement of Fibrosis and Resolution of NASH as a Composite Endpoint as Defined by Both Endpoints Being Met in the Same Participant | Proportion of participants with improvement of fibrosis and resolution of NASH as a composite endpoint as defined by both endpoints being met in the same participant at week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Baseline, Week 72 |
|
| |||||||||||||||||||||||||
| Secondary | Proportion of Participants With Resolution of NASH and no Worsening of Liver Fibrosis | Proportion of participants with resolution of NASH and no worsening of liver fibrosis at Week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
|
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| Secondary | Proportion of Participants With Histological Progression to Cirrhosis as Determined by Liver Biopsy | Proportion of participants with histological progression to cirrhosis as determined by liver biopsy at Week 72. | Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report. | Posted | Week 72 |
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| Secondary | Participants With TEAEs Leading to Discontinuation | Treatment emergent adverse events (TEAEs) were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug. TEAEs were regarded as leading to discontinuation if they led to discontinuation of the study drug. | Safety population (SAF) defined as all participants who received at least one dose of study drug. Participants were included in the treatment group that corresponded to the study drug received during the study. | Posted | Count of Participants | Participants | Day 1 to Week 72 |
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| Secondary | Percentage Change of Fat in the Liver From Baseline | Percentage change of fat in the liver as assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF) from Baseline to Week 12. | Intent-to-treat (ITT) Population: The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 24, n =17 and n= 26 for EDP-305 1.5, 2mg and Placebo groups respectively, presented as LS Mean (95% CI). | Posted | Least Squares Mean | 95% Confidence Interval | Percentage change | Baseline, Week 12 |
|
| ||||||||||||||||||||||
| Secondary | Change in Liver Stiffness From Baseline | Change in liver stiffness by magnetic resonance elastography (MRE) in kilopascal (kPa) from Baseline at Week 12. | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 24, n = 17 and n = 26 for EDP-305 1.5, 2mg groups and Placebo, respectively, presented as LS Mean (95% CI). | Posted | Least Squares Mean | 95% Confidence Interval | Kilopascal (kPa) | Baseline, Week 12 |
|
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| Secondary | Change in Triglycerides From Baseline | Change in Triglycerides from Baseline at Week 12. | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26 and n=30 for EDP-305 1.5, 2mg groups and Placebo respectively. | Posted | Mean | Standard Deviation | Millimoles per liter (mmol/L) | Baseline, Week 12 |
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| Secondary | Change in Adiponectin From Baseline | Change in adiponectin from Baseline at Week 12. | Safety population: Safety population (SAF) defined as all participants who received at least one dose of study drug. Participants were included in the treatment group that corresponded to the study drug received during the study. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 27, n = 24, and n = 27 for EDP-305 1.5 mg and 2 mg groups and Placebo respectively. | Posted | Mean | Standard Deviation | Micrograms per liter (µg/L) | Baseline, Week 12 |
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| Secondary | Plasma Concentration of EDP-305 | Plasma concentration at second post dose (2-4 hours post dose) at Week 12. | Pharmacokinetic (PK) Population: All participants receiving active study drug and having any measurable plasma concentration of study drug at any timepoint. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 6 and n = 7 for EDP-305 1.5 and 2mg groups respectively. | Posted | Mean | Standard Deviation | Nanograms per milliliter (ng/mL) | 2-4 hours post dose at Week 12 |
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| Secondary | Change in VAS (Visual Analog Score) From Baseline | Change in VAS from Baseline at Week 12. Change from baseline was analyzed using a restricted maximum likelihood-based MMRM technique. Two separate scales were used to assess pruritus. An itch VAS was used to record the intensity of the pruritus by Furue (Furue et al., 2013). Scale referred to no pruritus (0 point) and the end of the scale to the most severe pruritus (10 points). If the VAS score was greater than zero (i.e. itch), a multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. It was used to assess five different dimensions of pruritus within the last two weeks. The five dimensions assessed were duration, degree, direction, disability, and distribution. The total 5D itch score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus). | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 25 and n= 30 for EDP-305 1.5, 2mg groups and Placebo, respectively, presented as LS Mean (95% CI). | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Week 12 |
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| Secondary | Change in Total Cholesterol From Baseline | Change in Total Cholesterol from Baseline to Week 12 versus placebo. | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26, and n = 30 for EDP-305 1.5, 2 mg groups and Placebo respectively. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Week 12 |
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| Secondary | Change in HDL From Baseline | Change in HDL from Baseline at week 12. | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 27, n = 25, and n = 30 for EDP-305 1.5, 2 mg groups and Placebo respectively. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Week 12 |
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| Secondary | Change in LDL From Baseline | Change in LDL From Baseline to Week 12. | Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26, and n = 30 for EDP-305 1.5 mg, 2mg groups and Placebo respectively. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Week 12 |
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Day 1 to Week 72
Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
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 | EDP-305 1.5 mg | Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet | 0 | 32 | 2 | 32 | 28 | 32 |
| EG001 | EDP-305 2 mg | Once a day orally for 72 weeks EDP-305 2 mg: Tablet | 0 | 33 | 0 | 33 | 31 | 33 |
| EG002 | Placebo | Once a day orally for 72 weeks Placebo: Tablet | 0 | 32 | 0 | 32 | 20 | 32 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA Version 24.1 | Systematic Assessment |
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| Lipase increased | Investigations | MedDRA Version 24.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA Version 24.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA Version 24.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA Version 24.1 | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA Version 24.1 | Systematic Assessment |
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| Post vaccination syndrome | Injury, poisoning and procedural complications | MedDRA Version 24.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 24.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 24.1 | Systematic Assessment |
|
No limitations reported for the study.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alaa Ahmad | Enanta Pharmaceuticals, Inc | 1-617-607-0800 | aahmad@enanta.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 14, 2022 | Oct 28, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000709367 | EDP-305 |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Canada |
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| United States |
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| United Kingdom |
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| OG002 | Placebo | Once a day orally for 72 weeks Placebo: Tablet |
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| Counts |
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| Participants |
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| Participants |
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| OG001 | EDP-305 2 mg | Once a day orally for 72 weeks EDP-305 2 mg: Tablet |
| OG002 | Placebo | Once a day orally for 72 weeks Placebo: Tablet |
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