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

• ClinicalTrials.gov Identifier: NCT04104321
• Recruitment Status: Suspended
• First Posted: September 26, 2019
• Last Update Posted: August 4, 2022
• Sponsor: Galmed Research and Development, Ltd.
• Information provided by (Responsible Party): Galmed Pharmaceuticals Ltd ( Galmed Research and Development, Ltd. )

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.

Condition or disease	Intervention/treatment	Phase
Nonalcoholic Steatohepatitis (NASH)	Drug: Aramchol; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 23, 2019
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: June 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Aramchol; Aramchol 300 mg oral tablet	Drug: Aramchol; Aramchol 300 mg BID
Placebo Comparator: Placebo; Placebo matching oral tablet	Drug: Placebo; Placebo BID

Outcome Measures

Primary Outcome Measures :

1. Open label part: Kinetics of histological outcome measures [ Time Frame: Up to 72 or 120 weeks ]

   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).
2. Double Blind Part: To evaluate the effect of Aramchol compared to placebo on liver histology by assessing the following primary endpoints: [ Time Frame: 72 weeks ]
   • 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.
3. Double Blind Part: To evaluate the effect of Aramchol compared to placebo on composite long-term outcome [ Time Frame: at End of Study, latest at 5 years from last subject's randomization ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Male or female age 18 to 75 years
2. 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)
3. 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)
4. Fibrosis Stage must be 2 or 3 (Open-Label Part may include up to 30 subjects with fibrosis stage 1)
5. Body mass index (BMI) between 25kg/m2 and 40 kg/m2 (Open Label part: BMI <40 kg/m2)
6. AST>20 IU/L
7. Type 2 diabetes mellitus or prediabetes (Open Label Part only: Type 2 diabetes or prediabetes is not an inclusion criteria)
8. For subjects with type 2 diabetes, glycemia must be controlled
9. Females of childbearing potential must practice a highly effective method of contraception throughout the study period and for 1 month after treatment discontinuation.
10. Able to understand the nature of the study and to provide signature of the written informed consent.

Key Exclusion Criteria:

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

Contacts and Locations

Locations

United States, Florida

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

Miami, Florida, United States, 33136

United States, Texas

Texas Clinical Research Institute, LLC

Arlington, Texas, United States, 76012

Sponsors and Collaborators

Galmed Research and Development, Ltd.

More Information

• Responsible Party: Galmed Research and Development, Ltd.
• ClinicalTrials.gov Identifier: NCT04104321
• Other Study ID Numbers: Aramchol-018
• First Posted: September 26, 2019
• Last Update Posted: August 4, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Galmed Pharmaceuticals Ltd ( Galmed Research and Development, Ltd. ):

fibrosis; liver fibrosis; diabetes; obesity

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Diseases; Digestive System Diseases