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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02652377




Registration number
NCT02652377
Ethics application status
Date submitted
6/01/2016
Date registered
11/01/2016
Date last updated
23/01/2017

Titles & IDs
Public title
EDP-494-001: A Study of EDP-494 in Healthy Subjects and Hepatitis C Patients
Scientific title
A Randomized, Double-Blind, Pbo-Controlled, Study of EDP-494 to Evaluate the Safety and PK of SAD/FE in Healthy Subjects and MAD in Healthy and in Subjects With CHC Infection (POC)
Secondary ID [1] 0 0
EDP-494-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EDP-494
Treatment: Drugs - Placebo

Experimental: EDP-494 SAD Cohorts - EDP-494, oral 50 mg, 100mg, 200mg, 400mg and 800 mg, capsules, once daily in one single administration

Experimental: EDP-494 MAD/POC Cohorts - EDP-494, oral 200mg, 400mg and 800 mg, capsules, once daily for 14 days

Placebo Comparator: EDP-494 SAD Placebo Cohort -

Placebo Comparator: EDP-494 MAD/POC Placebo Cohort -


Treatment: Drugs: EDP-494
10, 100 and 200 mg capsules

Treatment: Drugs: Placebo
placebo to match EDP-494

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, and abnormal clinical laboratory results administered to healthy volunteers and multiple doses of EDP-494 - Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, echo and abnormal clinical laboratory results (including chemistry, hematology, and urine).
Administered to healthy volunteers and multiple doses of EDP-494 administered to healthy volunteers and subjects with Chronic Hepatitis C (CHC) genotype 1 and 3 infection
Timepoint [1] 0 0
From screening and baseline to the 4 week follow-up visit
Secondary outcome [1] 0 0
Cmax - EDP-494 and metabolites
Timepoint [1] 0 0
0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72 (Day 4), 96 (Day 5), 120 (Day 6)*, 144 (Day 7) and 168 (Day 8) hrs postdose
Secondary outcome [2] 0 0
Cmax - EDP-494 and metabolites
Timepoint [2] 0 0
Day 1: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15 hrs; Days 2, 3, 5, 7, 9, 12: 0 (Predose); Day 14: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72, 96, 120, 144 and 168 hrs postdose
Secondary outcome [3] 0 0
AUC - EDP-494 and metabolites
Timepoint [3] 0 0
0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72, 96, 120*, 144, and 168 hrs postdose
Secondary outcome [4] 0 0
AUC - EDP-494 and metabolites
Timepoint [4] 0 0
Day 1: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15 hrs; Days 2, 3, 5, 7, 9, 12: 0 (Predose);Day 14: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72, 96, 120, 144 and 168 hrs postdose
Secondary outcome [5] 0 0
Change from baseline in plasma HCV RNA (log10 IU/mL)
Timepoint [5] 0 0
Baseline up to 14 days
Secondary outcome [6] 0 0
Amino Acid Changes in HCV polymerase NS5b
Timepoint [6] 0 0
Baseline up to 3 months

Eligibility
Key inclusion criteria
Inclusion Criteria for Healthy Volunteers (SAD and MAD Phases):

- Healthy male and female subjects of any ethnic origin between the ages of 18 and 55
years, inclusive.

- Female subjects must be of non-childbearing potential.

- All male participants who have not had a vasectomy must use effective contraception
from Day -1 to 90 days after their last dose of study drug.

- Body mass index of 18 to 30 kg/m2 with a minimum body weight of 50 kg.

- An informed consent document signed and dated by the subject.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria for Healthy Volunteers (SAD and MAD Phases):

- Clinically relevant evidence or history of illness or disease

- Pregnant or nursing females.

- History of febrile illness within 7 days prior to the first dose of study drug or
subjects with evidence of active infection.

- A positive urine drug screen at screening or Day -1.

- Any condition possibly affecting drug absorption (e.g., gastrectomy).

- History of regular alcohol consumption

- Participation in a clinical trial within 30 days prior to study drug administration.

- Use of prescription drugs, non-prescription drugs, dietary supplements, herbal
supplements, hormonal therapy/replacement or CYP3A4 substrates, inducers and
inhibitors within 14 days prior to the first dose of study medication

Inclusion Criteria for HCV-Infected Subjects (POC Phase):

- Males and females aged 18 years and less than 70 years.

- Female subjects must be of non-childbearing potential.

- All male participants who have not had a vasectomy must use effective contraception
from Day -1 to 90 days after their last dose of study drug.

- Body mass index of 18 to 36 kg/m2 with a minimum body weight of 50 kg.

- Treatment naïve subjects with chronic HCV infection,

- HCV GT1 (including 1a, 1b, or mixed subtypes of GT1) or GT3.

- HCV RNA =100,000 IU/mL at screening.

- An informed consent document signed and dated by the subject.

Exclusion Criteria for HCV-Infected Subjects (POC Phase):

- Women of childbearing potential (WOCBP).

- Pregnant or nursing females.

- History of febrile illness within 7 days prior to the first dose of study drug.

- A positive urine drug screen at screening unless on an approved prescription.

- History of participation in a clinical trial with a polymerase inhibitor or previous
treatment with a polymerase inhibitor, where at least one dose of the polymerase
inhibitor was consumed. Subjects who were dosed with placebo on a clinical trial may
be enrolled in this study.

- Clinically significant electrocardiogram abnormalities or QTcF greater than 450 msec
for males and 470 msec for females at either screening or baseline, or any prior
history of QT abnormality.

- Co-infection with HIV-1, HIV-2 or HBV.

- Have clinically significant laboratory abnormalities at screening:

- Absolute neutrophil count (ANC) < 1500/mm2 (1.5 x 109L)

- Platelets <90,000/mm2 (90 x 109L)

- Hemoglobin < 13g/dL for males and < 12g/dL for females

- Serum creatinine >1.5 x upper limit of normal (ULN) or creatinine clearance < 50
mL/min; estimated by the cockcroft -Gault formula [(140-age) x weight (kg)/72 x
serum creatinine (mg/dL), if female multiply by 0.85]

- Total bilirubin greater than the ULN

- Serum alanine transaminase (ALT) > 5 x ULN

- Serum aspartate aminotransferase (AST) > 5 x ULN

- Alkaline phosphatase > 1.25 x ULN

- Pancreatic Amylase > 1.1 x ULN

- Alpha fetoprotein (AFP) > 50 ng/mL unless a liver imaging study (CT, MRI) shows
no clinically significant lesions within 6 months prior to the first dose of
study drug.

- Patients with evidence of cirrhosis; cirrhosis is defined as any one of the following:
a) any biopsy showing cirrhosis (Knodell score <3, Metavir score <3, Ishak score <4);
b) Fibroscan evaluation within 6 months prior to screening with a liver stiffness
score of ><12.5 kPa.

- Other significant, unstable or uncontrolled medical history, such as neurological,
endocrine, malignancy, renal, psychiatric, respiratory, cardiac, gastrointestinal,
allergic, immunological, etc. disease.

- Use of concomitant medications, including vitamins or herbal and dietary supplements
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study
medication

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Enanta Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, double-blind study will assess the safety, pharmacokinetics and efficacy of
a single and multiple dose(s) of orally QD administered EDP-494 in healthy volunteers (HV)
and in treatment-naive subjects with GT1/3 chronic hepatitis C (CHC) infection.
Trial website
https://clinicaltrials.gov/show/NCT02652377
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Edward Gane, MD
Address 0 0
Auckland Clinical Studies (ACS),
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications