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Trial registered on ANZCTR


Registration number
ACTRN12614000307606
Ethics application status
Approved
Date submitted
10/03/2014
Date registered
24/03/2014
Date last updated
17/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label study to investigate the safety and efficacy of treatment with ACH-0143102 and sofosbuvir in hepatitis C patients
Scientific title
A phase 2, open-label, randomized, controlled, partial crossover study to evaluate the efficacy, safety and tolerability of 8 weeks or 6 weeks of ACH-0143102 and sofosbuvir in treatment-naive subjects with chronic hepatitis C genotype-1 viral infection
Secondary ID [1] 284197 0
Protocol Number ACH102-017
Universal Trial Number (UTN)
U1111-1153-5593
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 291302 0
Condition category
Condition code
Infection 291655 291655 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active treatment is ACH-0143102 (2 x 25mg capsules) and sofosbuvir (1 x 400mg tablet) to be taken orally once a day.

The study is divided into 2 groups and will enrol up to 36 people. The study will initially randomize 18 subjects in an open label fashion into two treatment groups: Group 1A and Group 1B. Twelve (12) subjects will receive active treatment (50 mg ACH-0143102 + 400 mg sofosbuvir) starting on Day 1 for 8 weeks (Group 1A), and be followed for an additional 24 weeks. The other 6 subjects (Group 1B) will have a 12 week observational period, in which they will receive no treatment. Group 2 will only proceed if 100% of the subjects in Group 1A have virus not detected in the blood at 4 weeks after treatment is finished. A total of approximately 18 subjects could participate in Groups 2A and 2B. Up to six subjects from Group 1B will enter Group 2A. In addition, 12 new subjects will be randomized (1:1) in an open label fashion to either Group 2A (active treatment with 50 mg of ACH-0143102 + 400 mg of sofosbuvir for 6 weeks) or to Group 2B (observational period). Subjects in Groups 1B or 2B who received no treatment will be offered either 6 or 8 weeks of the same regime, depending on the results of the Groups 1A and 2A. Every patient will be checked throughout the study to ensure that the treatment is working and to record any side effects

Medication compliance will be monitored by tablet/capsule count at each study visit.

Subjects randomized to the 8 week regime will be required to attend clinic visits on 17 occasions over a 32 week period - a screening visit, a day 1 (baseline visit), a visit once a week for 8 weeks, and then for 8 follow up visits (at week 10, 12, 16, 20, 24, 28 and 32).
Those subjects who are randomised to the observation period will not be required to attend clinic after week 12.

Subjects randomized to the 6 week regime will be required to attend clinic visits on 15 occasions over a 30 week period - a screening visit, a day 1 (baseline visit), a visit once a week for 6 weeks, and then for 7 follow up visits (at week 8, 10, 14, 18, 22, 26 and 30. Those subjects who are randomised to the observation period will not be required to attend clinic after week 10.


Follow up visits will include a range of assessments (vital signs, pregnancy tests, safety laboratory tests, ECGs, adverse event assessments, concomitant medication review) and PK sampling.

No washout period is required as the only participants who are permitted to cross over are participants who did not receive any treatment.
Intervention code [1] 288895 0
Treatment: Drugs
Comparator / control treatment
Observation group will receive no treatment.

Once the week 12 HCV RNA results from Group 1A have been reviewed by Achillion Pharmaceuticals, Inc., sites will be informed how subjects in the observational group will proceed according to this algorithm:

1. If Sustained Virologic Response (SVR) is less than 90% at the week 12 time point for subjects in Group 1A, no further enrollment will occur, and subjects in Group 1B will receive appropriate standard of care, provided they were compliant with the protocol.
2. If SVR is greater than or equal to 90% but less than 100% at the week 12 time point for subjects in Group 1A, then subjects in Group 1B will be eligible to crossover from the observational treatment period and receive the same treatment as subjects in Group 1A (8 weeks of active treatment with 50 mg of ACH-0143102 + 400 mg of sofosbuvir) followed by 24 weeks of follow-up.
3. If 100% SVR is achieved at the 12 week time point for subjects in Group 1A, the 6 subjects who were in Group 1B, will be eligible to crossover into Group 2A and receive 6 weeks of active treatment with 50 mg of ACH-0143102 plus 400 mg of sofosbuvir

Once the week 10 HCV RNA results from Group 2A have been reviewed by Achillion Pharmaceuticals, Inc., sites will be informed how subjects in the observational group will proceed according to this algorithm:

If SVR is less than 90% at the EOT+4 week time point for subjects in Group 2A, then subjects in Group 2B will crossover from the observational period and receive the same treatment as subjects in Group 1A (8 weeks of active treatment with 50 mg of ACH-0143102 + 400 mg of sofosbuvir) followed by 24 weeks of follow-up.
2. If SVR is greater than or equal to 90% at the EOT+4 time point for subjects in Group 2A, then subjects in Group 2B will crossover from the observational period and receive the same treatment as subjects in Group 2A (6 weeks of active treatment with 50 mg of ACH-0143102 plus 400 mg of sofosbuvir) with 24 weeks of follow-up.

The standard of care provided to subjects will be determined by the principal investigator and will be the most effective available treatment for genotype 1 hepatitis C infection at the time of the study.

In order for the HCV RNA analyses to take place, there may be a time delay (days or weeks) between the end of the “observation” period and the next treatment course for patients in Group 1B/2B.
Control group
Active

Outcomes
Primary outcome [1] 291583 0
To determine the incidence of sustained virologic response (SVR) in subjects who received 8 weeks of active treatment.

This will be assessed by HCV RNA analysis on blood samples.
Timepoint [1] 291583 0
12 weeks after the completion of dosing
Primary outcome [2] 291585 0
To determine the incidence of sustained virologic response (SVR) in subjects who received 6 weeks of active treatment.

This will be assessed by HCV RNA analysis on blood samples.
Timepoint [2] 291585 0
12 weeks after the completion of dosing
Secondary outcome [1] 307125 0
To determine the safety and tolerability of 8 weeks of ACH-0143102 in combination with sofosbuvir in subjects with genotype-1 viral infection. Assessed by collection of adverse event data, laboratory tests, ECG, echocardiogram, vital signs, physical examination
Timepoint [1] 307125 0
Safety will be assessed at weeks 1,2,3,4,5,6,7,8, 10, 12, 16, 20, 24, 28 and 32
Secondary outcome [2] 307126 0
To determine the safety and tolerability of 6 weeks of ACH-0143102 in combination with sofosbuvir in subjects with genotype-1 viral infection. Assessed by collection of adverse event data, laboratory tests, ECG, echocardiogram, vital signs, physical examination
Timepoint [2] 307126 0
Safety will be assessed at weeka 1,2,3,4,5,6,8,10,14,18,22,26 and 30.
Secondary outcome [3] 307127 0
To determine the incidence of sustained virologic response in subjects who received active treatment for either 6 or 8 weeks.
This will be assessed via HCV RNA analysis on blood samples.
Timepoint [3] 307127 0
4, 8 and 24 weeks after the completion of dosing

Eligibility
Key inclusion criteria
- Chronic HCV infection
- HCV GT-1
- HCV RNA greater than 10,000 IU/mL at screening
- Signed and dated written consent
- Treatment naive subjects
- Biopsy or fibroscan confirming no evidence of cirrhosis
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- BMI greater than 36kg/m2
- Pregnant or lactating females. Men whose female partners are pregnant or contemplating pregnancy
- Clinically significant laboratory abnormality at screening
- Known HIV infection
- Positive hepatits B surface antigen
- History of participation in a clinical trial with pegylated interferon, RBV, or a direct-acting anti-viral agent, or previous treatment with any of these where at least one dose was taken
- Use of dietary supplements, herbal supplements, potent PGP inducers in the intestine, anticonvulsants, antimycobacterials and HIV protease inhibitors.

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 randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation generated by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Due to the exploratory nature of this study, no power or sample size calculations were performed. The number of subjects was chosen on an empirical basis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/03/2014
Actual
31/03/2014
Date of last participant enrolment
Anticipated
Actual
9/04/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
36
Recruitment outside Australia
Country [1] 5863 0
New Zealand
State/province [1] 5863 0
Auckland

Funding & Sponsors
Funding source category [1] 288824 0
Commercial sector/Industry
Name [1] 288824 0
Achillion Pharmaceuticals, Inc
Country [1] 288824 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] 287519 0
Commercial sector/Industry
Name [1] 287519 0
Clinical Network Services Ltd
Address [1] 287519 0
PO Box 78312, Grey Lynn, Auckland 1245
Country [1] 287519 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290664 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 290664 0
Ministry of Health
PO Box 5013
Wellington 6011
Ethics committee country [1] 290664 0
New Zealand
Date submitted for ethics approval [1] 290664 0
20/02/2014
Approval date [1] 290664 0
10/03/2014
Ethics approval number [1] 290664 0
14/NTB/24

Summary
Brief summary
This study will evaluate whether 6 or 8 weeks treatment with two antiviral agents, Sofosbuvir and ACH0143102, will be safe and effective in patients infected with Hepatitis C genotype 1 who have never been treated.

The study is divided into 2 groups and will enrol up to 36 people.

The study will initially randomize 18 subjects in an open ­label fashion into two treatment groups: Group 1A and Group 1B. Twelve (12) subjects will receive active treatment (50 mg ACH­0143102 + 400 mg sofosbuvir) starting on Day 1 for 8 weeks (Group 1A), and be followed for an additional 24 weeks. The other 6 subjects (Group 1B) will have a 12 week observational period, in which they will receive no treatment.

Group 2 will only proceed if 100% of the subjects in Group 1A have virus not detected in the blood at 4 weeks after treatment is finished. A total of approximately 18 subjects could participate in Groups 2A and 2B.
Up to six subjects from Group 1B will enter Group 2A. In addition, 12 new subjects will be randomized (1:1) in an open ­label fashion to either Group 2A (active treatment with 50 mg of ACH­0143102 + 400 mg of sofosbuvir for 6 weeks) or to Group 2B (observational period).

Subjects in Groups 1B or 2B who received no treatment will be offered either 6 or 8 weeks of the same regime, depending on the results of the Groups 1A and 2A.

Every patient will be checked throughout the study to ensure that the treatment is working and to record any side­ effects
Trial website
None
Trial related presentations / publications
NA. Analysis ongoing
Public notes

Contacts
Principal investigator
Name 46510 0
Prof Edward Gane
Address 46510 0
Auckland Clinical Studies Ltd
PO Box 8963
Symonds Street
Auckland 1150
Country 46510 0
New Zealand
Phone 46510 0
+64 9 373 3474
Fax 46510 0
Email 46510 0
[email protected]
Contact person for public queries
Name 46511 0
Mr Michael Mader
Address 46511 0
Achillion Pharmaceuticals Inc
300 George Street
New Haven CT 06511
Country 46511 0
United States of America
Phone 46511 0
+1 203-752-5441
Fax 46511 0
Email 46511 0
[email protected]
Contact person for scientific queries
Name 46512 0
Dr Hetal Kocinsky
Address 46512 0
Achillion Pharmaceuticals Inc
300 George Street
New Haven CT 06511
Country 46512 0
United States of America
Phone 46512 0
+1 203 752 5490
Fax 46512 0
Email 46512 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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.