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An Open-Label Study to Assess the Hepatic Protection Effect of SNP-612, in Patients With NAFLD

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ClinicalTrials.gov Identifier: NCT03868566
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Sinew Pharma Inc.

Brief Summary:
The primary objective of the study is to compare the changes in ALT to baseline among patients with non-alcoholic fatty liver disease (NAFLD) following the 3-month treatment of 3 different dosing regimens of SNP-612. The secondary objectives will be to compare the changes in other liver function tests, cytokeratin-18 (CK-18) fragment level and adverse event / serious adverse event rates.

Condition or disease Intervention/treatment Phase
NASH - Nonalcoholic Steatohepatitis Drug: SNP-612 dose1 Drug: SNP-612 dose2 Drug: SNP-612 dose3 Not Applicable

Detailed Description:

An open-label study will be conducted in several medical centers around Taiwan. The objective of the study is to investigate the efficacy and safety of SNP-612 for the treatment of NAFLD, assuming the treatment efficacy of the investigational product is superior to baseline.

Subjects who fulfill all the entry criteria and have written informed consent will be enrolled to the study. Considering a 10% drop-out rate, approximately 54 subjects will be enrolled for screening in order to recruit 48 evaluable subjects to complete the enrollment.

Subjects will be administered the study agent oral daily for 3 months or until treatment terminates prematurely. Subjects will return to the study center for clinical evaluation once every 4 weeks throughout the treatment period. Clinical assessment procedures and laboratory tests including ultrasound imaging, hematology with differential, biochemistry, liver function panel, and urinalysis, will be performed at each study visit. The primary endpoint assessment will be the reduction of ALT, at completion of Week 12 compared to baseline. With 48 evaluable patients, 16 patients of each arm, there will be an 80% chance of detecting a significant difference at a two sided 0.05 significance level. This assumes a greater reduction of mean ALT changed from baseline by at least -25 U/L difference in patients taking the test drug compared to those of the control group, with a standard deviation at 40 U/L.Subjects who finish treatment or discontinue prematurely from the study for any reason after receiving one or more doses of study agent will be assessed for safety for 4 weeks after the last study agent dose or longer in the case of any significant AE or abnormal biochemical or clinical finding. Clinical laboratory tests will be measured once monthly during the follow-up period. Subjects will be required to return to the study center for at least one clinical evaluation following 2 (±1) weeks after the end of treatment or early termination, that is, the end-of-study visit.

Each subject will participate in the study for approximately 14 weeks (including the enrollment/baseline visit, 3 routine monthly visits during treatment period, and 1 follow-up visit after 2 weeks of the end of treatment). It is assumed the study will include a 6-month enrollment period and further 4 months to complete the follow-up for all enrolled patients.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Experimental: SNP-612 dose1 Experimental: SNP-612 dose2 Experimental: SNP-612 dose3
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study to Assess the Hepatic Protection Effect of a Food Supplement Product, SNP-612, in Patients With Non-alcoholic Fatty Liver Disease
Actual Study Start Date : August 4, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: SNP-612 dose1
dose1 once a day orally for 12 weeks
Drug: SNP-612 dose1
Subjects will take dose1 once a day orally for 12 weeks

Experimental: SNP-612 dose2
dose2 once a day orally for 12 weeks
Drug: SNP-612 dose2
Subjects will take dose2 once a day orally for 12 weeks

Experimental: SNP-612 dose3
dose3 once a day orally for 12 weeks
Drug: SNP-612 dose3
Subjects will take dose3 once a day orally for 12 weeks




Primary Outcome Measures :
  1. Change in serum ALT [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition


Secondary Outcome Measures :
  1. Change in serum AST [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition

  2. Change in serum Alk-P [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition

  3. Change in serum γ-GT [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition

  4. Change in GSP [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition

  5. Change in liver fat content as measured by liver fat fraction (FF) with magnetic resonance imaging method. [ Time Frame: 12 weeks ]
    A non-invasive method will be utilized to estimate liver fat content (%) by MRI calculated liver FF.

  6. Change in serum CK-18 fragment levels [ Time Frame: 12 weeks ]
    A reduction from baseline (i.e. a negative percent value) indicates an improvement in condition

  7. Rate of AE/SAE [ Time Frame: 12 weeks ]
    Rate of patients who experience AE/SAE at end of treatment

  8. Rate of AEs leading to discontinuation at end of treatment [ Time Frame: 12 weeks ]
    Rate of patients who experience AEs leading to discontinuation at end of treatment


Other Outcome Measures:
  1. Insulin resistance [ Time Frame: 12 weeks ]
    Change in insulin resistance at Week 12

  2. Triglycerides [ Time Frame: 12 weeks ]
    Change in serum at Week 12

  3. Low density lipoprotein [ Time Frame: 12 weeks ]
    Change in serum at Week 12

  4. Total cholesterol [ Time Frame: 12 weeks ]
    Change in serum at Week 12

  5. High density lipoprotein [ Time Frame: 12 weeks ]
    Change in serum at Week 12

  6. Gene expression biomarkers [ Time Frame: 12 weeks ]
    Gene expression biomarkers (ACC1, Adfp, AOX, Cat, CCL20, CCR2, Cpt1α, CYP2E1, CYP4A11, CYP7A, Dgat1, Dgat2, FAS, Gapdh, Gpx1, Gpx2, Gpx3, Gpx4, GSS, Hadh, Ho1, HSL, IL-10, IL-1β, IL-6, iNOS, LCAD, NF-κB1, NF-κB2, Pparα, PPARβ/δ, PPARγ, SCD-1, Sod1, Sod2, Sod3, SREBP-1c, TGFβ, TLR4, TNFα, Ucp2, VLCAD, α-SMA, β-actin) related to NASH changes in blood at Week 12



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 20 years
  2. Body weight ≥ 54 kg
  3. Diagnosis of non-alcoholic steatohepatitis (NASH) as evidenced by imaging or other diagnostic assessments. Subjects should have documented liver fat content ≥ 10.0 % as measured by MRI method prior to study agent administration.
  4. Alanine aminotransferase (ALT) levels ≥ 2.0x upper limit of normal (ULN) on at least two occasions, seven or more days apart, prior to study agent administration.
  5. Have adequate organ functions as defined by the following examinations prior to the start of study agent administration.

    1. Hematology: Hemoglobin ≥ 9 g/dL, a platelet count ≥ 100 x 10^9/L, and a white blood cell count ≥ 3.0 x 10^9/L
    2. Renal: creatinine clearance >= 90 mL/min (by Cockcroft-Gault equation), serum uric acid < 9.0 mg/dL
  6. Able to provide written informed consent, and understand and comply with the requirements of the study

Exclusion Criteria:

  1. Decompensated or severe liver disease as evidenced by one or more of the following:

    1. Confirmed cirrhosis or suspicion of cirrhosis
    2. Liver transplant
    3. Liver malignancy
    4. Ascites
    5. Bilirubin >2 x ULN, or ALT or AST > 10 x ULN
    6. Acute or chronic hepatitis A, B, C, HIV, or other liver diseases affecting liver function.

    Patients with cysts, hemangiomas, or similar abnormalities, are accepted.

  2. History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 glasses of 120-mL wine or 14 cans of 350-mL beer), or other substance abuse within the prior two years
  3. Subjects who are unable to undergo an MRI scan.
  4. Subjects have electronically, magnetically and mechanically activated implanted devices, including but not limited to automatic cardioverter defibrillators, cardiac pacemakers, insulin pumps, metallic splinters in the eye, ferromagnetic hemostatic clips in central nervous systems or vascular vessels.
  5. Significant systemic or major illness other than liver disease, including auto-immune disease, coronary artery disease, cerebrovascular disease, malignant neoplasms, pulmonary disease, renal insufficiency, serious psychiatric disease, and/or other serious diseases, that, in the opinion of the Investigator would preclude the subject from participating in and completing the study
  6. Documented history of serious allergic reaction to SNP-612 or any structurally related compounds
  7. Diabetic patients who have not maintained a stable dose of oral medication for hyperglycemia or have had more than 10 percent change in their insulin dose over the past two months
  8. Regular use of agents that are potent against hepatitis or affecting lipid metabolisms, including but not limited to HMG-CoA reductase inhibitors (statins), fibrates, silymarin, N-acetylcysteine, or anti-TNF therapies.

    Note: refer to Section 6.5 Prohibited agents for details.

  9. Pregnant or lactating
  10. Female of child-bearing potential who are not committed to taking reliable contraception during the participation in the study and at least 4 weeks after the end of the study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03868566


Contacts
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Contact: Chen-Che Su, MS 0910633800 h2243398@sinewpharma.com

Locations
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Taiwan
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 114
Contact: Chen-Che Su, MS    0910633800    h2243398@sinewpharma.com   
Principal Investigator: Yu-Lueng Shih, MD,PhD         
Sponsors and Collaborators
Sinew Pharma Inc.
Investigators
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Principal Investigator: Yu-Lueng Shih, MD,PhD Tri-Service General Hospital

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Responsible Party: Sinew Pharma Inc.
ClinicalTrials.gov Identifier: NCT03868566     History of Changes
Other Study ID Numbers: SNP-612-202
First Posted: March 11, 2019    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases