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

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ClinicalTrials.gov Identifier: NCT04104321
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
Galmed Pharmaceuticals Ltd ( Galmed Research and Development, Ltd. )

Tracking Information
First Submitted Date  ICMJE September 18, 2019
First Posted Date  ICMJE September 26, 2019
Last Update Posted Date February 17, 2021
Actual Study Start Date  ICMJE September 23, 2019
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2021)
  • 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).
  • 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.
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 24, 2019)
  • To evaluate the effect of Aramchol compared to placebo on liver histology by assessing the following primary endpoints: [ Time Frame: 52 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.
  • 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).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR)
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Nonalcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • Drug: Aramchol
    Aramchol 300 mg BID
  • Drug: Placebo
    Placebo BID
Study Arms  ICMJE
  • Experimental: Aramchol
    Aramchol 300 mg oral tablet
    Intervention: Drug: Aramchol
  • Placebo Comparator: Placebo
    Placebo matching oral tablet
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2019)
2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2027
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Galmed +972-3-6938448 clinicaltrial@galmedpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04104321
Other Study ID Numbers  ICMJE Aramchol-018
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Galmed Pharmaceuticals Ltd ( Galmed Research and Development, Ltd. )
Study Sponsor  ICMJE Galmed Research and Development, Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Galmed Pharmaceuticals Ltd
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP