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Suspended by sponsor, pending investigation of abnormal laboratory values in patients with NASH
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This phase 2, double blind, placebo-controlled, randomized study is to assess the safety and efficacy of miricorilant (CORT118335) in patients with presumed Nonalcoholic Steatohepatitis (NASH).
This is a randomized, double-blind, placebo-controlled study that assessed the safety efficacy and pharmacokinetics (PK) of miricorilant in patients with presumed Nonalcoholic Steatohepatitis (NASH). Patients who meet the criteria for Study CORT118335-860 were randomized on Day 1 to receive 900 mg miricorilant, 600 mg miricorilant, or placebo for 12 weeks.
Due to observations related to safety, the study was terminated prior to completion and study objectives, endpoints, and procedures were modified as specified in the protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Miricorilant- 900 mg | Experimental | Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. |
|
| Miricorilant- 600 mg | Experimental | Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. |
|
| Placebo | Placebo Comparator | Participants received 6 placebo tablets orally once daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Miricorilant | Drug | Tablets taken orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change From Baseline in Liver Fat Content Assessed by Magnetic Resonance Imaging-Proton Density Fat Fraction | The change from baseline in liver fat content (LFC) by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for each miricorilant dose level (600 mg, 900 mg) versus placebo was assessed. MRI-PDFF was performed to determine the degree of LFC reduction. The relative change is defined for each participant as %: ([Post-Baseline LFC-Baseline LFC]/Baseline LFC) × 100. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and up to ~Day 95 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving a Relative Reduction From Baseline in LFC of ≥30% by MRI-PDFF | The number of participants (defined as responders) with a ≥30% reduction in LFC from baseline by treatment group as assessed by MRI-PDFF. The number of participants with a reduction in LFC from baseline of <30% were defined as non-responders. MRI-PDFF was performed at screening and up to 33 days after last dose of study drug. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Relative Reduction in Liver Fat Content ≥50% by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) for Miricorilant Versus Placebo | Baseline and up to ~Day 95 | |
| Number of Participants With Complete Resolution in Liver Fat by MRI-PDFF for Miricorilant Versus Placebo |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Director | Corcept Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 207 | Chandler | Arizona | 85224 | United States | ||
| Site 208 |
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Twelve adult patients with presumed NASH were enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Miricorilant- 900 mg | Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. |
| FG001 | Miricorilant- 600 mg | Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. |
| 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 | Dec 7, 2020 | Jul 6, 2022 |
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| Placebo | Drug | Placebo tablets |
|
| Baseline and up to ~Day 95 |
| Change From Baseline in Aspartate Aminotransferase | The change in aspartate aminotransferase (AST) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and Week 6 |
| Change From Baseline in Alanine Aminotransferase | The change in serum alanine aminotransferase (ALT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and Week 6 |
| Change From Baseline in Gamma-glutamyl Transferase | The change in gamma-glutamyl transferase (GGT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and Week 6 |
| Change From Baseline in Propeptide of Type III Collagen | The change in serum propeptide of Type III collagen (pro-C3) from baseline at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and Week 6 |
| Change From Baseline in Enhanced Liver Fibrosis Score | The change in enhanced liver fibrosis (ELF) from baseline for each treatment group at the Week 6 visit is summarized. The ELF score combines 3 serum biomarkers (hyaluronic acid, tissue inhibitor of metalloproteinases-1 [TIMP-1] and type III procollagen [PIIINP]) which have been shown to correlate with the degree of liver fibrosis assessed by liver biopsy. Each of these markers is measured by an immunoassay and an ELF score is generated [ELF=2.278+0.851 ln(HA)+0.751 ln(PIIINP)+0.394 ln(TIMP-1)], from which a level of fibrosis severity can be determined; higher ELF scores are associated with worsening liver fibrosis. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | Baseline and Week 6 |
| Baseline and up to ~Day 95 |
| Glendale |
| Arizona |
| 85306 |
| United States |
| Site 209 | Tucson | Arizona | 85712 | United States |
| Site 227 | Los Angeles | California | 90057 | United States |
| Site 214 | Panorama City | California | 91402 | United States |
| Site 233 | Santa Ana | California | 92704 | United States |
| Site 234 | Port Orange | Florida | 32127 | United States |
| Site 210 | Sarasota | Florida | 34240 | United States |
| Site 228 | Kansas City | Missouri | 61434 | United States |
| Site 232 | East Syracuse | New York | 13057 | United States |
| Site 211 | Austin | Texas | 78757 | United States |
| Site 213 | Edinburg | Texas | 78539 | United States |
| Site 215 | Edinburg | Texas | 78539 | United States |
| Site 212 | San Antonio | Texas | 78229 | United States |
| Site 226 | Seattle | Washington | 98105 | United States |
| FG002 | Placebo | Participants received 6 placebo tablets orally once daily. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Miricorilant- 900 mg | Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. |
| BG001 | Miricorilant- 600 mg | Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. |
| BG002 | Placebo | Participants received 6 placebo tablets orally once daily. |
| 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, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Liver Fat Content (LFC) Assessed by MRI-PDFF | Mean | Standard Deviation | Percentage of liver fat content |
| |||||||||||||||
| Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) & Gamma Glutamyl Transferase (GGT) | Mean | Standard Deviation | Units/Liter (U/L) |
| |||||||||||||||
| Propeptide of Type III Collagen (Pro-C3) | Mean | Standard Deviation | micrograms/liter (μg/L) |
| |||||||||||||||
| Enhanced Liver Fibrosis Score | Mean | Standard Deviation | ELF score |
|
| 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 | Relative Change From Baseline in Liver Fat Content Assessed by Magnetic Resonance Imaging-Proton Density Fat Fraction | The change from baseline in liver fat content (LFC) by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for each miricorilant dose level (600 mg, 900 mg) versus placebo was assessed. MRI-PDFF was performed to determine the degree of LFC reduction. The relative change is defined for each participant as %: ([Post-Baseline LFC-Baseline LFC]/Baseline LFC) × 100. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline LFC assessment. | Posted | Mean | Standard Deviation | Percent change | Baseline and up to ~Day 95 |
|
|
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants Achieving a Relative Reduction From Baseline in LFC of ≥30% by MRI-PDFF | The number of participants (defined as responders) with a ≥30% reduction in LFC from baseline by treatment group as assessed by MRI-PDFF. The number of participants with a reduction in LFC from baseline of <30% were defined as non-responders. MRI-PDFF was performed at screening and up to 33 days after last dose of study drug. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline LFC assessment. | Posted | Count of Participants | Participants | Baseline and up to ~Day 95 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Aspartate Aminotransferase | The change in aspartate aminotransferase (AST) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline AST assessment. | Posted | Mean | Standard Deviation | units per liter (U/L) | Baseline and Week 6 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Alanine Aminotransferase | The change in serum alanine aminotransferase (ALT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline ALT assessment. | Posted | Mean | Standard Deviation | U/L | Baseline and Week 6 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Gamma-glutamyl Transferase | The change in gamma-glutamyl transferase (GGT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline GGT assessment. | Posted | Mean | Standard Deviation | U/L | Baseline and Week 6 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Propeptide of Type III Collagen | The change in serum propeptide of Type III collagen (pro-C3) from baseline at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline pro-C3 assessment. | Posted | Mean | Standard Deviation | μg/L | Baseline and Week 6 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Enhanced Liver Fibrosis Score | The change in enhanced liver fibrosis (ELF) from baseline for each treatment group at the Week 6 visit is summarized. The ELF score combines 3 serum biomarkers (hyaluronic acid, tissue inhibitor of metalloproteinases-1 [TIMP-1] and type III procollagen [PIIINP]) which have been shown to correlate with the degree of liver fibrosis assessed by liver biopsy. Each of these markers is measured by an immunoassay and an ELF score is generated [ELF=2.278+0.851 ln(HA)+0.751 ln(PIIINP)+0.394 ln(TIMP-1)], from which a level of fibrosis severity can be determined; higher ELF scores are associated with worsening liver fibrosis. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups. | The analysis population included all participants who were randomized to the study and had a post-baseline liver fibrosis assessment. | Posted | Mean | Standard Deviation | ELF score | Baseline and Week 6 |
| |||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With a Relative Reduction in Liver Fat Content ≥50% by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) for Miricorilant Versus Placebo | Posted | Count of Participants | Participants | Baseline and up to ~Day 95 |
|
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Complete Resolution in Liver Fat by MRI-PDFF for Miricorilant Versus Placebo | Posted | Count of Participants | Participants | Baseline and up to ~Day 95 |
|
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Up to ~Day 95 for all cause mortality, serious adverse events and other non-serious treatment-emergent adverse events (TEAEs) during the study period.
The analysis population included all patients who received at least 1 dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Miricorilant- 900 mg | Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG001 | Miricorilant- 600 mg | Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. | 0 | 5 | 0 | 5 | 5 | 5 |
| EG002 | Placebo | Participants received 6 placebo tablets orally once daily. | 0 | 4 | 0 | 4 | 1 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Muscle rupture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Electrocardiogram abnormal | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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Due to observations related to safety, the study was terminated by the Sponsor prior to completion. The sample size at the time of study termination did not support formal tests to assess statistical differences between treatment groups, and therefore, no efficacy analyses specified in the protocol were performed. Descriptive statistics for efficacy endpoints are provided, but since no patient reached the Week 12 visit, and therefore, descriptive statistics at Week 12 are not presented.
No individual publications will be allowed before publication of the multicenter results, except as agreed with the Sponsor. The Investigator agrees to submit all manuscripts or abstracts to the Sponsor for review before submission to the publisher.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Corcept Therapeutics Incorporated | 650-327-3270 | info@corcept.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2021 | Jul 6, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000606526 | CORT118335 |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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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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| ALT |
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| GGT |
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Participants received 6 placebo tablets orally once daily.
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| Participants |
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| Participants |
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Participants received 6 placebo tablets orally once daily. |
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