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Trial registered on ANZCTR


Registration number
ACTRN12614000304639
Ethics application status
Approved
Date submitted
7/03/2014
Date registered
21/03/2014
Date last updated
13/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Oral ACH-0143422 after Single and Multiple-ascending Doses in Health Volunteers and Subjects With Chronic Hepatitis C Virus Genotype 1 Infection.
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Oral ACH-0143422 after Single and Multiple-ascending Doses in Health Volunteers and Subjects With Chronic Hepatitis C Virus Genotype 1 Infection.
Secondary ID [1] 284210 0
ACH422 001
Universal Trial Number (UTN)
U1111-1154-1699
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
This current study is being conducted in healthy volunteers to learn about the way this drug behaves in the body when it is given at different doses. The study will also be conducted in patients with Hepatitis C genotype 1. 291315 0
Condition category
Condition code
Infection 291668 291668 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active treatment is ACH-0143422 or placebo taken at the following dosages and frequencies:

In healthy volunteers:
Group 1A: single dose of 50mg FED
Group 1B: single dose of 50mg FASTED
Group 2A: single dose of 150mg FED
Group 2B: single dose of 150mg FASTED
Group 3: single dose of 300 mg FED
Group 4A: single dose of 500 mg FED
Group 4B: single dose of 700 mg FED

Group 5: 50mg, once daily for 14 days
Group 6: up to 150mg, once daily for 14 days
Group 7: up to 300mg, once daily for 14 days
Group 8A: 500 mg, once daily for 14 days FASTED
Group 8B: 500 mg, once daily for 14 days FED
Group 8C: 700 mg, once daily for 14 days FED

In Hepatitis C patients:
Group 9: 50mg, once daily for 7 days
Group 10: up to 150mg, once daily for 7 days
Group 11: up to 300mg, once daily for 7 days
Group 12A: 500 mg, once daily for 14 days FED
Group 12B: 700 mg, once daily for 14 days FED
Group 12C: GT3 subjects, 700 mg, once daily for 14 days FED
Group 12D: GT2 subjects, 700 mg, once daily for 14 days FED

Groups 3-12D will be either fed or fasted, depending on the results from previous groups.

ACH 0143422 or placebo will be administered orally for all participants in all parts of the trial. All treatments for healthy volunteers and treatments up to Day 8 for HCV patients will be administered in the clinic to ensure compliance.
Intervention code [1] 288905 0
Treatment: Drugs
Comparator / control treatment
Placebo (Microcrystalline cellulose capsule).
Control group
Placebo

Outcomes
Primary outcome [1] 291605 0
To evaluate the safety, tolerability, and pharmacokinetic (PK) profile of ACH-0143422 in healthy volunteers following the administration of single-ascending oral doses

Safety and tolerability will be assessed via adverse events, laboratory tests, ECGs, vital signs and physical examinations.
PK analysis wil be assessed via blood samples.
Timepoint [1] 291605 0
7 days after dosing (day 7)
Primary outcome [2] 291606 0
To demonstrate the safety, tolerability, and PK of ACH 0143422 in healthy volunteers following oral administration for 14 days in multiple, ascending dose groups

Safety and tolerability will be assessed via adverse events, laboratory tests, ECGs, vital signs and physical examinations.
PK analysis wil be assessed via blood samples.
Timepoint [2] 291606 0
7 days after last dose (day 21)
Primary outcome [3] 291607 0
To determine the antiviral activity and viral kinetics of ACH 0143422 in HCV-infected subjects following oral administration of multiple ascending doses for 7 days

Antiviral activity will be assessed via virology tests on blood samples. Blood samples will be analysed for HCV RNA levels.
Timepoint [3] 291607 0
7 days after last dosing (day 14)
Secondary outcome [1] 307153 0
To assess the effect of food on PK of ACH 0143422 administered as a single dose under fed and fasted conditions in healthy volunteers

This will be assessed by analysing the plasma exposures observed from the PK sampling (blood tests) from Groups 1 and 2.
Timepoint [1] 307153 0
7 days after dosing (day 7)
Secondary outcome [2] 307154 0
To evaluate initial HCV viral kinetics in subjects who have received ACH 0143422

To be assessed via virology testing of blood samples.
Timepoint [2] 307154 0
7 days after last dose (day 14)
Secondary outcome [3] 307155 0
To monitor for the development of drug resistant variants, and assess changes in HCV genotype and phenotype in HCV-infected subjects who receive ACH 0143422.

To be assessed via virology testing of blood samples.
Timepoint [3] 307155 0
7 days after last dosing (day 14)
Secondary outcome [4] 307325 0
[PRIMARY OUTCOME]
To demonstrate the safety, tolerability and PK of ACH 0143422 in subjects infected with hepatitis C virus (HCV) following oral administration of multiple ascending doses for 7 days

To be assessed via testing of blood samples
Timepoint [4] 307325 0
[PRIMARY TIMEPOINT]
7 days after dosing

Eligibility
Key inclusion criteria
Inclusion criteria for Healthy Volunteers:

1. Between 18 and 55 years old
2.No clinically relevant health abnormalities
3.Agree to use effective contraception (defined in the protocol)4. HCV GT-1 (Groups 9, 10, 11, 12A and 12B), HCV GT-3 (Group 12C) and HCV GT-2 (Group 12D) including all subtypes, mixed subtypes or subtypes undetermined
5.Body mass index of 18 to 30 kg/m2 with a minimum body weight of 50 kg

Inclusion criteria for patients:

1. Aged 18 to less than 70 years old
2. Treatment naive subjects with chronic HCV infection
3. BMI of 18 to 36 kg/m2 with a minimum body weight of 50 kg
4.HCV genotype 1 (including 1a, 1b, or mixed subtypes of genotype 1)
5.HCV RNA greater or equal to 10,000 IU/mL at screening
Minimum age
18 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria for healthy volunteers:

1. History of any clinically relevant illness or clinically significant laboratory abnormalities or ECG (defined in the protocol)
2. Pregnant or nursing females
3. Febrile illness within 7 days of first dose of study drug
4. Current Smoker
5. Positive urine drug screen at day 0-1
6. Regular alcohol consumption
7. Any condition possibly affecting drug absorption (e.g., gastrectomy)
8. Use of prescription drugs, non-prescription drugs, dietary supplements, herbal supplements, and hormonal therapy/replacement, or ingestion of foods which are CYP3A4 substrates, inducers and inhibitors within 14 prior to the first dose of study medication unless approved by the Investigator and Sponsor

Exclusion criteria for patients:

As above and also including:
1. 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
2. Co-infection with HIV-1, HIV-2 or HBV
3. Subjects with a history of liver disease

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)
Central randomization via a computer-generated paper list or Interactive Web Response System (IWRS)
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/04/2014
Actual
30/04/2014
Date of last participant enrolment
Anticipated
8/05/2015
Actual
2/04/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
157
Accrual to date
Final
151
Recruitment outside Australia
Country [1] 5867 0
New Zealand
State/province [1] 5867 0

Funding & Sponsors
Funding source category [1] 288833 0
Commercial sector/Industry
Name [1] 288833 0
Achillion Pharmaceuticals, Inc
Country [1] 288833 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Achillion Pharmaceuticals, Inc
Address
300 George Street
New Haven, CT 06511
Country
United States of America
Secondary sponsor category [1] 287527 0
Commercial sector/Industry
Name [1] 287527 0
Clinical Network Services Ltd
Address [1] 287527 0
PO Box 78312, Grey Lynn, Auckland 1245
Country [1] 287527 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290673 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 290673 0
Ethics committee country [1] 290673 0
New Zealand
Date submitted for ethics approval [1] 290673 0
06/03/2014
Approval date [1] 290673 0
24/03/2014
Ethics approval number [1] 290673 0

Summary
Brief summary
This study is divided into three phases. The first two phases are being conducted in healthy volunteers. The third phase will be conducted in patients who have been diagnosed with Hepatitis C genotype 1.

The first phase of the study will evaluate the safety, tolerability and pharmacokinetics of four single doses of ACH 0143422 or placebo (50mg, 150mg, 300mg or 500mg). This first part will also examine the different absorption rates between fed and fasted groups and these results will inform how patients are dosed in the rest of the trial.

The second phase will evaluate the safety ,tolerability and pharmacokinetics of four different dosing regiments of ACH0143422 or placebo (50mg, 150mg, 300mg or 500mg) taken once a day for 14 days.

The third phase of the study will be conducted in HCV positive patients and will evaluate safety ,tolerability and pharmacokinetics of four different dosing regimens of ACH0143422 or placebo (50mg, 150mg, 300mg or 500mg) taken once a day for 7 days. It will also examine the effect the study drug/placebo has on the HCV viral load.
Trial website
Trial related presentations / publications
Public notes
One of the trial’s primary outcomes has been listed as a ‘Secondary Outcome’ field set due to the ANZCTR form being unable to display more than three ‘Primary Outcome’ field sets.

Contacts
Principal investigator
Name 46730 0
Prof Edward Gane
Address 46730 0
Auckland Clinical Studies Ltd PO Box 8963 Symonds Street Auckland 1150
Country 46730 0
New Zealand
Phone 46730 0
+64 9 373 3474
Fax 46730 0
Email 46730 0
[email protected]
Contact person for public queries
Name 46731 0
John Lahey
Address 46731 0
Achillion Pharmaceuticals Inc 300 George Street New Haven CT 06511
Country 46731 0
United States of America
Phone 46731 0
+1 203-752-5437
Fax 46731 0
+1 203-624-7003
Email 46731 0
[email protected]
Contact person for scientific queries
Name 46732 0
John Lahey
Address 46732 0
Achillion Pharmaceuticals Inc 300 George Street New Haven CT 06511
Country 46732 0
United States of America
Phone 46732 0
+1 203-752-5437
Fax 46732 0
+1 203-624-7003
Email 46732 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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