Ascending Dose Study of HU6 in Healthy Volunteers

NCT04463017 | Completed Phase 1 FDA Drug

• 1 other identifier: RIV-HU6-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single ascending dose trial in healthy volunteers. The study will be conducted in up to 7 cohorts. Upon review of the safety and PK data, it may be decided to expand the current cohort versus dose escalate to the next cohort. In addition, the sponsor may elect not to enroll all 7 cohorts based on safety and/or PK and/or PD data.

Conditions

NASH - Nonalcoholic Steatohepatitis

Keywords

NASH

Outcome Measures

Primary Outcomes (2)

• Assess the dose relationship of PK Parameter Cmax

  Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for Cmax analyzed

  3 months

• Assess the dose relationship of PK Parameter AUC

  Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for AUC analyzed

  3 months

Study Arms (2)

Active Treatment: HU6

ACTIVE COMPARATOR

Planned doses of HU6; N = 74

Drug: HU6

Placebo Comparator

PLACEBO COMPARATOR

Non-active study drug N = 14

Drug: HU6

Interventions

HU6 DRUG

HU6 is designed to reduce the steatosis, inflammation, fibrosis and hepatocyte injury in Noncirrhotic Nonalcoholic Steatohepatitis (NASH)

Active Treatment: HU6; Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18 and 45 years of age, inclusive, at time of informed consent.
• Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative urine pregnancy test at Screening and admission to Clinical Research Unit, and using, and agree to continue using, an effective method of contraception for at least 4 weeks prior to first study drug administration until 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 post-menopausal (no menses for \>1 year with follicle stimulating hormone \>40 U/L at Screening)
• 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.
• 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.
• Healthy per investigator judgment as documented by medical history, physical examination, vital sign assessments, 12-lead ECG, clinical laboratory assessments, and general observations.
• At Screening, abnormalities or deviations outside the normal ranges for any clinical assessments that are considered clinically significant by the Investigator (laboratory tests, ECG, vital signs) may be repeated once at the discretion of the Investigator(s), and 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.
• On admission to Clinical Research Unit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and thyroid values must be within the upper limits of the normal range. Subjects with isolated elevation of bilirubin and presumptive Gilbert's syndrome are permissible. All other laboratory test results that are outside the reference range on admission to CRU and judged by the investigator to be not clinically significant may optionally be repeated. Results that continue to be outside the reference range must be judged by the investigator to be not clinically significant and acceptable for study participation.
• Subject must demonstrate clinical euthyroidism as assessed by a thyroid profile utilizing TSH and Free T4 testing at screening.
• a. Body mass index \> 30.0 kg/m2, waist circumference \> 41"
• 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 presenting with any of the following will not qualify for entry into the study:
• Current or past clinically significant history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease, as determined by the investigator. History of cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within 5 years prior to Screening.
• Any surgical or medical condition or history that, in the opinion of the investigator, may potentially alter the absorption, metabolism, or excretion of study treatment, such as, but not limited to gastric bypass surgery or small bowel resections.
• Contraindication to study drug or its excipients and/or history of allergic or anaphylactic reactions.
• Resting heart rate \<45 or \>100 bpm; blood pressure \< 90 or \>140 systolic, or \<50 or \>100 diastolic.
• On screening ECG and by history:
• A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration of a QTc 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).
• Taking any of the following prohibited medications:
• For non-obese cohorts:
• a. Any prescription medication (with the exception of all hormonal contraceptives and hormone replacement therapies (oral, injectable, transdermal or implanted)) or over the counter multi-vitamin supplement, including products with CBD or any non-prescription products (including herbal-containing preparations but excluding acetaminophen) within 14 days prior to admission to CRU.
• For obese cohort:
• a. Limited background prescription medications are permitted to manage complications of obesity, but any drug known to inhibit or induce cytochrome P450 (CYP) enzymes and/or P-glycoprotein including St. John's wort (Hypericum perforatum) within 14 days or 5 half-lives (whichever is longer) prior to admission to CRU, is prohibited. Also prohibited is the use of concomitant medications that prolong the QT/QTc interval identified in the https://crediblemeds.org/ website list category of 'Known Risk'.
• History of significant drug abuse within one year prior to Screening or use of soft drugs (such as marijuana) within 3 months prior to the Screening visit or hard drugs (such as cocaine, phencyclidine \[PCP\], opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
• History of regular alcohol consumption exceeding 14 drinks/week \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor\] within 6 months of Screening.

Sponsors & Collaborators

• Rivus Pharmaceuticals, Inc.: lead

Study Sites (1)

Prism Clinical Research

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Mark Matson, MD

  Prism Research Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in one phase: a single dose, dose escalation phase in up to 7 cohorts

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 9, 2020
• Study Start: August 12, 2020
• Primary Completion: March 30, 2021
• Study Completion: April 1, 2021
• Last Updated: May 4, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)