A Multiple Ascending Dose Phase I Study of SB 9200 in Treatment Naïve Adults With Chronic Hepatitis C Infection

September 17, 2019 updated by: Syneos Health

A Phase 1a/1b Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of SB 9200 in Treatment Naïve HCV Infected Adults

The purpose of this study is to compare the safety and tolerability of ascending doses of SB 9200 given for up to 14 days to subjects with chronic Hepatitis C infection.

Study Overview

Status

Completed

Detailed Description

This is a First-in-human, Two-stage, Multi-centre study. Part A is an open-label, single ascending dose study in fed or fasted subjects and Part B is a randomized, placebo-controlled multiple ascending dose study. The study is designed to evaluate the safety and tolerability of ascending doses of SB 9200 given as monotherapy for up to 14 days to subjects with chronic Hepatitis C infection, and to determine the pharmacokinetic and pharmacodynamic relationship over this dose range.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Nucleus Network, Austin Hospital
      • Melbourne, Victoria, Australia, 3004
        • Nucleus Network, The Alfred Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Linear Clinical Research, The Queen Elizabeth II Medical Centre
      • Christchurch, New Zealand, 8011
        • Primorus Clinical Trials Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must provide written informed consent before any assessment is performed.
  • Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Males or females of non-childbearing potential between the ages of 18 and 60 years, inclusive.
  • Must have HCV and laboratory evidence of HCV infection for at least six months before the Screening Visit.
  • Must have HCV-1 (1a or 1b or non-sub-typeable HCV-1), HCV-2 or HCV-3, as applicable for a given cohort.
  • Subjects must have a plasma HCV RNA >5 log10 IU/mL (100,000 IU/mL).
  • Must have fibrosis of Stage 2 or lower by Ishak or Metavir scoring system or equivalent as evidenced by a recent (within two years of screening) liver biopsy (i.e. no more than moderate fibrosis). If a recent liver biopsy is not available, Fibroscan of < 8.5 kilopascals at screening.
  • Must have negative human immunodeficiency virus (HIV) and Hepatitis B screening test results.
  • Must have a body mass index (BMI) of 18-32 kg/m2 (inclusive).
  • Must have screening laboratory values within the reference ranges or if outside the normal range, not clinically significant as judged by the Investigator. ALT and aspartate aminotransferase (AST) must be within 2x the upper limit of normal.
  • Must not consume grapefruit or grapefruit-related citrus fruits or juice from seven days prior to the first dose of study drug until collection of the final PK blood sample at 14 days after the last dose of study drug.
  • Must be able to communicate with site personnel and understand instructions.

Exclusion Criteria:

  • Any previous treatment with an investigational or approved drug or drug regimen for the treatment of HCV. Note: SB 9200 is excluded from this criterion, i.e. subjects who complete Part A of the study will be eligible to participate in Part B of the study.
  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
  • Use of nonprescription drugs, vitamins and dietary supplements within 14 days or five half-lives (whichever is longer) prior to the trial dose medication. Changes to prescription medication within 14 days prior to the first dose of study medication (i.e. only stable prescription medications are permitted whilst on study).
  • History of intercurrent illness (e.g., upper respiratory illness with fever) within five days prior to the first dose of study drug.
  • History of illicit or controlled substance abuse or alcohol abuse within one year before the Screening Visit (with the exception of cannabinoids).
  • Any condition possibly affecting drug absorption (e.g., gastrectomy).
  • Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at screening or baseline.
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five years, regardless of whether there is evidence of local recurrence or metastases.
  • Women of child-bearing potential.
  • Fertile males, defined as all males physiologically capable of conceiving offspring unless the subject and partner of child bearing potential agree to comply with acceptable contraception and the female partner is not lactating.
  • Prior liver biopsy (at any time in the past), indicating Stage 3 or higher fibrosis by Ishak or Metavir scoring system or equivalent (i.e. greater than moderate fibrosis).
  • Any other cause of significant liver disease in addition to HCV, which may include, but is not limited to, malignancy with hepatic involvement, hepatitis B, drug or alcohol related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, or primary biliary cirrhosis.
  • Evidence or history or clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  • Blood donation of approximately 500 mL or significant blood loss within 56 days prior to dosing.
  • Any other medical or psychiatric condition or laboratory abnormality which, in the view of the Investigator, is likely to interfere with the study or put the subject at risk.
  • Concurrent participation in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Part A

Experimental: Part A: Part A will use a single ascending dose protocol in small, open-label cohorts to determine the starting dose for Part B in the potentially therapeutic range.

Intervention: SB9200

Part A open-label, single ascending doses of SB9200 from 100mg - 1500mg.
Part B randomised 6:2 (active:placebo) using recommended Part B starting dose, and ascending to up to 1500mg for 7-14 days of dosing.
Experimental: Experimental Part B

Experimental: Part B: Part B will use a multiple ascending dose protocol to further explore the safety, tolerability, pharmacokinetics and pharmacodynamics of SB9200 over 7-14 days of dosing.

Intervention: SB9200 and Placebo

Part A open-label, single ascending doses of SB9200 from 100mg - 1500mg.
Part B randomised 6:2 (active:placebo) using recommended Part B starting dose, and ascending to up to 1500mg for 7-14 days of dosing.
Part B randomised 6:2 (active:placebo) using anhydrous lactose capsules identical to active comparator, minus active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: Up to 35 days
Clinical safety data from 12-lead ECG, clinical laboratory tests, urinalysis, treatment-emergent adverse events, vital signs (blood pressure, heart rate, respiratory rate).
Up to 35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic profile of SB9200
Time Frame: Up to 35 days
Pharmacokinetic parameters and the PK profile of SB 9200 at doses from 100 mg to 1500 mg given for up to 14 days to subjects with Hepatitis C.
Up to 35 days
Pharmacokinetic and Pharmacodynamic relationship of SB9200
Time Frame: Up to 35 days
Correlation between SB9200 exposure and Hepatitis C RNA level at doses from 100 mg to 1500 mg.
Up to 35 days
Effect of food on exposure of SB 9200
Time Frame: Up to 35 days
Comparison of exposure to SB9200 in fed and fasted states.
Up to 35 days
Short Term Antiviral Efficacy
Time Frame: Up to 35 days
Short term antiviral efficacy of ascending doses of SB 9200 monotherapy given for up to 14 days to treatment naïve subjects with Hepatitis C.
Up to 35 days
Viral Resistance
Time Frame: Up to 35 days
Viral resistance and describe any resistant mutants that appear during Investigational Product administration.
Up to 35 days
IL28B Genotype
Time Frame: Up to 35 days
Association of IL28B genotype (CC, CT or TT) with virologic response to SB 9200 at the chosen dose.
Up to 35 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory: IFN Expression and IFN pathways
Time Frame: Up to 35 days
Blood samples will be collected for potential exploratory evaluation of correlations between SB9200 dose and Interferon (IFN) expression, and induction of signalling proteins in IFN pathways such as Interferon Regulatory Factor (IRF)-3, IRF-7, Interferon Stimulated Gene 15 (ISG15) and Extra Erythrocytically expressed haemoglobin (EEEH) levels in plasma.
Up to 35 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Donald Mitchell, F-star Therapeutics, Inc.
  • Principal Investigator: Alexander Thompson, MD, PhD, Nucleus Network, The Alfred Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

February 27, 2013

First Submitted That Met QC Criteria

February 28, 2013

First Posted (Estimate)

March 4, 2013

Study Record Updates

Last Update Posted (Actual)

September 18, 2019

Last Update Submitted That Met QC Criteria

September 17, 2019

Last Verified

August 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatitis C Infection

Clinical Trials on SB9200

3
Subscribe