Phase 2a Study of HU6 in Subjects With Elevated Liver Fat and High BMI Volunteers

NCT04874233 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RIV-HU6-203
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2a, randomized, parallel-group, placebo-controlled, double-blind, repeated-dose study to evaluate the safety and efficacy of three oral dose levels of HU6 compared to placebo over the course of 61 days in subjects with high BMI and evidence of elevated liver fat.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Change From Baseline in Liver Fat Content as Assessed by MRI-PDFF

  Percentage of Change from Baseline in Liver Fat Content as Assessed by MRI-PDFF at Day 61

  Baseline and 61 days;

Study Arms (4)

Active Treatment: HU6 150 mg; N = 20

ACTIVE COMPARATOR

HU6 is Active Study Drug

Drug: HU6

Active Treatment: HU6 300 mg; N = 20

ACTIVE COMPARATOR

HU6 is Active Study Drug

Drug: HU6

Active Treatment: HU6 450 mg; N = 20

ACTIVE COMPARATOR

HU6 is Active Study Drug

Drug: HU6

Placebo Comparator Non-active study drug N = 20

PLACEBO COMPARATOR

Non-active Study Drug

Drug: Placebo

Interventions

HU6 DRUG

HU6 is active study drug

Active Treatment: HU6 150 mg; N = 20; Active Treatment: HU6 300 mg; N = 20; Active Treatment: HU6 450 mg; N = 20

Placebo DRUG

Non-active study drug N = 20

Placebo Comparator Non-active study drug N = 20

Eligibility Criteria

• Age: 28 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Adult male or females, 28 to 65 years of age (inclusive) at the time of informed consent with BMI between 28.0 and 45.0 kg/m2 (inclusive).
• Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative urine pregnancy test at Screening and agree to continue using an effective method of contraception for at least 4 weeks or barrier method for 2 weeks prior to first study drug administration until 30 days after the last dose of study drug (Section 8.3.2).
• Female subjects of childbearing potential must not donate ova during the study and for at least 30 days after the last dose of study drug.
• Female subjects of non-childbearing potential must be surgically sterile (e.g., hysterectomy, bilateral tubal ligation, oophorectomy) or postmenopausal (no menses for \>1 year with follicle stimulating hormone (FSH) \>40 U/L at Screening).
• Male subjects who have not had a vasectomy and/or subjects who have had a vasectomy but have not had 2 post surgery negative tests for sperm must agree to use an acceptable method of contraception from time of first dose of study drug until 30 days after the last dose of the study drug, and to not donate sperm during the study and for at least 30 days after the last dose of study drug.
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• Subjects must be on stable doses of medications for underlying obesity-related conditions for at least 2 months prior to screening.
• Subjects with diabetes may be treated with metformin, DPP-4 inhibitors, or sulfonylureas, but must be on stable doses for at least 2 months prior to screening.
• At Screening, certain laboratory values may be outside the reference range if commensurate with the underlying obesity or associated metabolic dysfunction in the eligible subject (for example, dyslipidemia and hyperglycemia), unless these abnormalities suggest an underlying condition which may impact subject safety in the trial or interfere with the evaluation of HU6 or affect interpretation of the study results.
• Abnormalities or deviations outside the normal ranges for other assessments that are considered clinically significant by the Investigator (clinical laboratory tests, ECG, vital signs, physical examination) may be repeated once at the discretion of the Investigator(s). Results that continue to be outside the normal ranges must be judged by the investigator to be not clinically significant and acceptable for study participation.
• Subjects with elevation of unconjugated bilirubin due to presumptive Gilbert's syndrome are permissible.
• Subject must be euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone (TSH) and free thyroxine (T4) testing at screening. Subjects with a stable history of thyroid disease and who have been on stable doses of thyroid medications for a minimum of 4 months can be enrolled.
• \. Fibroscan® CAP score\>300 dB/m. 4. ≥8% liver fat by MRI-PDFF. 5. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.
• \. Willing and able to comply with the requirements of the study protocol.

You may not qualify if:

• Subjects will be excluded from the study if any of the following criteria are met:
• Insulin-controlled diabetes.
• Pregnant or breastfeeding or plans to become pregnant.
• Intolerance to Magnetic Resonance Imaging (MRI) or with conditions contraindicated for MRI procedures including but not limited to inability to fit into MRI scanner or surgical clips/metallic implants/shrapnel. Subjects must not be claustrophobic, have a history of claustrophobia, or intolerance of closed or small spaces.
• Weight gain or loss \>5% in 3 months prior to study or \>10% in 6 months prior to screening.
• History of lap banding, intragastric balloon, duodenal-jejunal sleeve, or bariatric surgery within 5 years of screening, plans for bariatric surgery prior to conclusion of study participation, or plans to lose weight during this study either through a special diet, exercise program or both.
• History of malignant hyperthermia.
• History of chronic serious recurrent skin rashes of unknown cause.
• History of or current clinically significant cardiovascular disease including but not limited to transient ischemic attack, stroke, cardiac arrhythmias, syncope, unstable angina, myocardial infarction in the 6 months prior to screening, congestive heart failure, or uncontrolled hypertension. (Uncontrolled hypertension is defined as a systolic blood pressure ≥160 mmHg or a diastolic blood pressure ≥100 mmHg based on an average of three resting determinations in the sitting position with an appropriately sized cuff).
• Resting heart rate \<45 or \>110 bpm.
• On screening ECG or by history:
• A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration of a QTcF interval \> 450 msec for males and \>470 msec for females).
• A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or a family history of sudden cardiac death of unknown origin.
• Kidney disease, kidney transplant, or estimated glomerular filtration rate (eGFR) \<50 mL/min/1.73 m2 based on the CKD-EPI Creatinine Equation (NKF 2009; https://www.kidney.org/content/ckd-epi-creatinine-equation-2009).
• Significant lung disease requiring chronic daily medication including chronic obstructive pulmonary disease (COPD), emphysema, pulmonary fibrosis, or asthma.

Sponsors & Collaborators

• Rivus Pharmaceuticals, Inc.: lead

Study Sites (1)

Prism Clinical Research

Minneapolis, Minnesota, 55114, United States

Location

Related Publications (1)

• Noureddin M, Khan S, Portell F, Jorkasky D, Dennis J, Khan O, Johansson L, Johansson E, Sanyal AJ. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Gastroenterol Hepatol. 2023 Dec;8(12):1094-1105. doi: 10.1016/S2468-1253(23)00198-X. Epub 2023 Oct 5.

  PMID: 37806314 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Amy Eastenson, MD
• Organization: Prism Clinical Research

aeastenson@prismresearchinc.com

1-651-641-2900

Study Officials

• Amy Eastenson

  Prism Clinic Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2021
• First Posted: May 5, 2021
• Study Start: April 19, 2021
• Primary Completion: November 30, 2021
• Study Completion: December 15, 2021
• Last Updated: March 1, 2024
• Results First Posted: March 1, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)