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A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR) (ARMOR)

Primary Purpose

Nonalcoholic Steatohepatitis (NASH)

Status

Suspended

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Aramchol

Placebo

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis (NASH) focused on measuring fibrosis, liver fibrosis, diabetes, obesity

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Male or female age 18 to 75 years
Histological confirmation of NASH on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period)
Total NAS Score 4 or more with at least 1 in each component of the NAS Score (steatosis ≥1 AND inflammation ≥1 AND ballooning ≥1)
Fibrosis Stage must be 2 or 3 (Open-Label Part may include up to 30 subjects with fibrosis stage 1)
Body mass index (BMI) between 25kg/m2 and 40 kg/m2 (Open Label part: BMI <40 kg/m2)
AST>20 IU/L
Type 2 diabetes mellitus or prediabetes (Open Label Part only: Type 2 diabetes or prediabetes is not an inclusion criteria)
For subjects with type 2 diabetes, glycemia must be controlled
Females of childbearing potential must practice a highly effective method of contraception throughout the study period and for 1 month after treatment discontinuation.
Able to understand the nature of the study and to provide signature of the written informed consent.

Key Exclusion Criteria:

Histologically documented liver cirrhosis (fibrosis stage 4)
Inability or unwillingness to undergo a liver biopsy
Abnormal synthetic liver function
ALT or AST >5× upper limit of normal (ULN)
Platelet count < 150,000mm3
Alkaline phosphatase ≥2× ULN
Known or suspected hepatocellular carcinoma (HCC)
Model for End-Stage Liver Disease (MELD) score > 12
Prior history or presence of decompensated liver disease
Other (acute or chronic) coexisting liver disease based on medical history and/or centralized review of liver histology)
Known alcohol and/or any other drug abuse or dependence in the last five years
Weight loss of more than 5% within 3 months prior to screening
History of bariatric surgery within 5 years of liver biopsy or planned surgery for weight reduction
Treatment with drugs that may cause NAFLD within 12 months prior to liver biopsy
Treatment with some anti-diabetic medications; Unless started prior to biopsy (timeframe depending on drug) and stable
Current or planned treatment with immunosuppressive drugs
Evidence of any other unstable or untreated clinically significant disease
Uncontrolled hypertension
Any other condition that in the opinion of the Investigator warrants exclusion from the study

Sites / Locations

The Public Health Trust of Miami-Dade County, Florida, dba the Jackson Health System
Texas Clinical Research Institute, LLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aramchol

Placebo

Arm Description

Aramchol 300 mg oral tablet

Placebo matching oral tablet

Outcomes

Primary Outcome Measures

Open label part: Kinetics of histological outcome measures

The primary endpoints are the kinetics of the following histological outcome measures for treatment duration of 24, 48 and 72 weeks and potentially following a 2nd post-baseline biopsy at weeks 72 or 96 or 120, respectively: Improvement in Fibrosis defined as the Proportion (%) of subjects with improvement in liver fibrosis greater than or equal to one stage (NASH CRN fibrosis score) and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation or steatosis) Resolution of NASH defined as the Proportion (%) of subjects with resolution of NASH (defined by ballooning of 0 and inflammation 0-1) and no worsening of liver fibrosis on NASH CRN fibrosis score (≥ 1 stage increase).

Double Blind Part: To evaluate the effect of Aramchol compared to placebo on liver histology by assessing the following primary endpoints:

Resolution of NASH defined as the Proportion (%) of subjects with resolution of NASH (defined by Ballooning of 0 and inflammation 0-1) and no worsening of liver fibrosis, or Improvement in Fibrosis defined as the Proportion (%) of subjects with improvement in liver fibrosis greater than or equal to one stage and no worsening of steatohepatitis.

Double Blind Part: To evaluate the effect of Aramchol compared to placebo on composite long-term outcome

Proportion (%) of subjects experiencing at least 1 of the following events: All-cause mortality, Liver transplant, Histological progression to cirrhosis, MELD score >15, Hospitalization due to hepatic decompensation event(s).

Secondary Outcome Measures

Full Information

NCT ID

NCT04104321

First Posted

September 18, 2019

Last Updated

August 2, 2022

Sponsor

Galmed Research and Development, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04104321

Brief Title

A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR)

Acronym

ARMOR

Official Title

A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With Nonalcoholic Steatohepatitis (NASH) With Open-Label Part to Evaluate the Safety, PK and Treatment Response Kinetics of Aramchol. The ARMOR Study

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Suspended

Why Stopped

Interim analysis of data from open-label part, showed this part of the study met its objectives, therefore decided to discontinue this part. Starting the double-blind part is being delayed due to Aramchol Meglumine being formulated.

Study Start Date

September 23, 2019 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Galmed Research and Development, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

An Open-Label Part is added: This part will enroll in selected sites which are less affected by the COVID-19 pandemic. 150 subjects with NASH and fibrosis confirmed by liver histology (F1-F3) will be randomized into 3 groups according to the post-baseline biopsy. The objective of the Open-Label Part is: To evaluate the safety and PK of twice daily administration (BID) of Aramchol 300mg in subjects with NASH and liver fibrosis. To explore the kinetics of histological outcome measures and Non-Invasive Tests (NITs) associated with NASH and fibrosis for the treatment duration of 24, 48 and 72 weeks. All patients will be allocated to Aramchol. Double Blind Part: This part is double blind, placebo controlled randomized in subjects with NASH and fibrosis stages 2-3 who are overweight or obese and have prediabetes or type 2 diabetes. The primary objectives of this part of the study are to evaluate the effect of Aramchol as compared to placebo on NASH resolution, fibrosis improvement and clinical outcomes related to progression of liver disease. Subjects will be randomized to receive Aramchol 300mg BID or matching placebo in a 2:1 randomization ratio.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nonalcoholic Steatohepatitis (NASH)

Keywords

fibrosis, liver fibrosis, diabetes, obesity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

In the Double-Blind part of the study, subjects will be randomized in a ratio of 2:1 to receive Aramchol 300mg BID or matching placebo, respectively. In the Open Label part of the study, there will be a single group of 150 subjects (expected) all receiving Aramchol 300mg BID.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

2000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Aramchol

Arm Type

Experimental

Arm Description

Aramchol 300 mg oral tablet

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo matching oral tablet

Intervention Type

Drug

Intervention Name(s)

Aramchol

Intervention Description

Aramchol 300 mg BID

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo BID

Primary Outcome Measure Information:

Title

Open label part: Kinetics of histological outcome measures

Description

Time Frame

Up to 72 or 120 weeks

Title

Double Blind Part: To evaluate the effect of Aramchol compared to placebo on liver histology by assessing the following primary endpoints:

Description

Time Frame

72 weeks

Title

Double Blind Part: To evaluate the effect of Aramchol compared to placebo on composite long-term outcome

Description

Time Frame

at End of Study, latest at 5 years from last subject's randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Male or female age 18 to 75 years Histological confirmation of NASH on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period) Total NAS Score 4 or more with at least 1 in each component of the NAS Score (steatosis ≥1 AND inflammation ≥1 AND ballooning ≥1) Fibrosis Stage must be 2 or 3 (Open-Label Part may include up to 30 subjects with fibrosis stage 1) Body mass index (BMI) between 25kg/m2 and 40 kg/m2 (Open Label part: BMI <40 kg/m2) AST>20 IU/L Type 2 diabetes mellitus or prediabetes (Open Label Part only: Type 2 diabetes or prediabetes is not an inclusion criteria) For subjects with type 2 diabetes, glycemia must be controlled Females of childbearing potential must practice a highly effective method of contraception throughout the study period and for 1 month after treatment discontinuation. Able to understand the nature of the study and to provide signature of the written informed consent. Key Exclusion Criteria: Histologically documented liver cirrhosis (fibrosis stage 4) Inability or unwillingness to undergo a liver biopsy Abnormal synthetic liver function ALT or AST >5× upper limit of normal (ULN) Platelet count < 150,000mm3 Alkaline phosphatase ≥2× ULN Known or suspected hepatocellular carcinoma (HCC) Model for End-Stage Liver Disease (MELD) score > 12 Prior history or presence of decompensated liver disease Other (acute or chronic) coexisting liver disease based on medical history and/or centralized review of liver histology) Known alcohol and/or any other drug abuse or dependence in the last five years Weight loss of more than 5% within 3 months prior to screening History of bariatric surgery within 5 years of liver biopsy or planned surgery for weight reduction Treatment with drugs that may cause NAFLD within 12 months prior to liver biopsy Treatment with some anti-diabetic medications; Unless started prior to biopsy (timeframe depending on drug) and stable Current or planned treatment with immunosuppressive drugs Evidence of any other unstable or untreated clinically significant disease Uncontrolled hypertension Any other condition that in the opinion of the Investigator warrants exclusion from the study

Facility Information:

Facility Name

The Public Health Trust of Miami-Dade County, Florida, dba the Jackson Health System

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Texas Clinical Research Institute, LLC

City

Arlington

State/Province

Texas

ZIP/Postal Code

76012

Country

United States

12. IPD Sharing Statement

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A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR)

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