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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02625909




Registration number
NCT02625909
Ethics application status
Date submitted
7/12/2015
Date registered
9/12/2015
Date last updated
13/06/2019

Titles & IDs
Public title
Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection.
Scientific title
A Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in People Who Inject Drugs and People With HIV Coinfection.
Secondary ID [1] 0 0
VHCRP1401
Universal Trial Number (UTN)
Trial acronym
REACT
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
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SOF/VEL for 6 weeks
Treatment: Drugs - SOF/VEL for 12 weeks

Experimental: Drug: SOF/VEL for 6 weeks - Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks.

Experimental: Drug: SOF/VEL for 12 weeks - Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks.


Treatment: Drugs: SOF/VEL for 6 weeks
Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).

Treatment: Drugs: SOF/VEL for 12 weeks
Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).

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

Outcomes
Primary outcome [1] 0 0
The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection (duration of infection less than or equal to 12 months) - To evaluate the proportion of participants with HCV RNA below the level of quantification at 12 weeks post end of treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection less than or equal to 12 months.
Timepoint [1] 0 0
12 weeks post treatment
Secondary outcome [1] 0 0
The proportion of participants with undetectable HCV RNA at end of treatment - To evaluate the proportion of participants with HCV RNA below the level of quantification at end of treatment
Timepoint [1] 0 0
End of treatment - week 6 of the shortened treatment duration arm, and week 12 of the standard treatment duration arm
Secondary outcome [2] 0 0
The proportion of participants with SVR4 (sustained virological response 4 weeks post treatment), defined as undetectable HCV RNA at 4 weeks post treatment - To evaluate the proportion of participants with HCV RNA below the level of quantification 4 weeks post treatment
Timepoint [2] 0 0
4 weeks post end of treatment
Secondary outcome [3] 0 0
The proportion of participants with SVR24 (sustained virological response 24 weeks post treatment), defined as undetectable HCV RNA at 24 weeks post treatment - To evaluate the proportion of participants with HCV RNA below the level of quantification 24 weeks post treatment
Timepoint [3] 0 0
24 weeks post treatment
Secondary outcome [4] 0 0
The proportion of participants with undetectable HCV RNA through two years post treatment - To evaluate the proportion of participants with HCV RNA below the level of quantification through 2 years post treatment
Timepoint [4] 0 0
Termination visit (week 102 for shortened treatment duration arm and week 108 for standard treatment duration arm)
Secondary outcome [5] 0 0
Treatment adherence - To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation)
Timepoint [5] 0 0
Baseline to week 6 (shortened treatment duration arm) or week 12 (standard treatment duration arm)
Secondary outcome [6] 0 0
Toxicity - To evaluate the proportion of participants with at least one severe or potentially life threatening (grade 3 or 4) adverse event
Timepoint [6] 0 0
Baseline through to 4 weeks post treatment (SVR4)
Secondary outcome [7] 0 0
Early treatment discontinuation - To evaluate the proportion of participants who discontinue therapy prior to the per-protocol planned end of treatment (6 or 12 weeks depending on the study arm)
Timepoint [7] 0 0
Baseline through to 6 or 12 weeks depending on the study arm
Secondary outcome [8] 0 0
Emergence of viral resistance associated variants (RAVs) - To evaluate the emergence of viral resistance-associated variants (RAVs). HCV sequencing will be conducted on the baseline EDTA (ethylenediaminetetraacetic acid) plasma samples of all participants to detect any baseline RAVs and will be conducted on the EDTA plasma samples of the participants who experienced virological relapse or breakthrough to detect the emergence of RAVs
Timepoint [8] 0 0
Baseline through to 6 or 12 weeks depending on the study arm
Secondary outcome [9] 0 0
HCV reinfection rate - To evaluate the rate of HCV reinfection during and up to 48 months following end of treatment
Timepoint [9] 0 0
Week 102 (for the shortened treatment duration arm) or 108 (for the standard treatment duration arm)

Eligibility
Key inclusion criteria
- Subjects must meet all of the following inclusion criteria to be eligible to
participate in this study:

1. Participants have voluntarily signed the informed consent form.

2. 18 years of age or older.

3. Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the
investigator is unlikely to demonstrate spontaneous viral clearance

4. HCV genotypes 1-6.

5. HBsAg negative

6. Compensated liver disease (Child-Pugh A)

7. Negative pregnancy test at baseline (females of childbearing potential only).

8. Medically stable on the basis of physical examination, medical history and vital
signs

9. Adequate English to provide reliable responses to the study questionnaires

10. All fertile males and females must be using effective contraception during
treatment and during the 30 days after treatment end.

11. Recently acquired HCV infection (estimated duration of infection =12 months)*

Recently acquired HCV infection as defined by:

A) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Documented
anti-HCV Ab negative within the 12 months prior to anti-HCV antibody positive result

OR

B) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Acute
clinical hepatitis [jaundice or alanine aminotransferase (ALT)] > 10 X ULN) within the
previous 6 months prior to first positive HCV antibody or HCV RNA, with no other cause of
acute hepatitis identifiable

OR

C) For cases of recent HCV reinfection the following criteria are required:

Documented prior HCV antibody positive with HCV RNA negative on at least 2 occasions 6
months apart AND new HCV RNA positive within the previous 6 months

*Estimated duration of infection based on midpoint between last antibody negative or HCV
RNA and first antibody positive or HCV RNA in the case of seroconversion and 6 weeks prior
to date of maximum ALT in the case of acute hepatitis.

If co-infection with HIV is documented, the subject must meet the following criteria:

1. Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with cluster of
differentiation 4 (CD4) T cell count >500 cells/mm3 OR

2. On a stable ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count
>200 cells/mm3 and an undetectable plasma HIV RNA level.

- Suitable ARV include:

- Tenofovir (TDF) and tenofovir alafenamide (TAF)

- Emtricitabine (FTC)

- Rilpivirine

- Dolutegravir

- Elvitegravir/cobicistat

- Contraindicated ARV include:

- Efavirenz 50% reduction in velpatasvir (GS-5816) exposure

- Didanosine

- Zidovudine

- Tipranavir Other ARV agents may be permissible at the time of study
commencement pending further drug-drug interaction studies; please discuss
with Study Principal Investigator.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Subjects who meet any of the exclusion criteria are not to be enrolled in this study.

1. History of any of the following:

1. Clinically significant illness (other than HCV) or any other major medical
disorder that may interfere with the participant treatment, assessment or
compliance with the protocol; participants currently under evaluation for a
potentially clinically significant illness (other than HCV) are also excluded.

2. History of chronic pulmonary disease associated with functional limitation,
severe cardiac disease, major organ transplantation or other evidence of severe
illness, malignancy, or any other conditions which would make the patient, in the
opinion of the investigator, unsuitable for the study

3. Solid organ transplant

4. Malignancy within 5 years prior to screening, with exception of specific cancers
that may have been cured by surgical resection (basal cell skin cancer, etc.).
Subjects under evaluation for possible malignancy are also excluded.

5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

2. Subject shows evidence of significant liver disease in addition to hepatitis C, which
may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune
hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis (NASH), or
primary biliary cirrhosis

3. Subject has known cirrhosis

4. Any of the following lab parameters at screening:

1. Direct bilirubin > 1.5 x ULN

2. Platelets < 50,000/µL

3. Creatinine clearance (CLcr) < 60 mL/min

4. Haemoglobin < 11 g/dL for females ; < 12 g/dL for males

5. Albumin < 30g/L

5. Pregnant or nursing female.

6. Use of prohibited concomitant medications as described in section 5.2 in the protocol

7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone
equivalent > 10 mg/day)

8. Known hypersensitivity to velpatasvir, sofosbuvir or formulation excipients.

9. Therapy with any anti-neoplastic or immunomodulatory treatment (including
supraphysiologic doses of steroids and radiation) =6 months prior to the first dose of
study drug.

10. Any investigational drug =6 weeks prior to the first dose of study drug.

11. Previous failure of therapy with sofosbuvir or an non-structural protein 5A (NS5A)
inhibitor prior to the first dose of study drug.

12. Ongoing severe psychiatric disease as judged by the treating physician.

13. Frequent injecting drug use that is judged by the treating physician to compromise
treatment safety.

14. Inability or unwillingness to provide informed consent or abide by the requirements of
the study.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Kirketon Road Centre - Sydney
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [3] 0 0
The Kirby Institute, University of New South Wales Australia - Sydney
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
1340 - Sydney
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
2052 - Sydney
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Germany
State/province [4] 0 0
Bonn
Country [5] 0 0
Netherlands
State/province [5] 0 0
Amsterdam
Country [6] 0 0
New Zealand
State/province [6] 0 0
Auckland
Country [7] 0 0
Switzerland
State/province [7] 0 0
Bern
Country [8] 0 0
United Kingdom
State/province [8] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The aim of the study is to determine if treatment for recently acquired hepatitis C infection
(with or without HIV coinfection) can be shortened when treating with the interferon-free
therapy sofosbuvir/velpatasvir (SOF/VEL).

SOF/VEL is a new treatment for hepatitis C called direct acting antiviral which targets the
hepatitis C virus replication cycle and has been shown in phase II studies in chronic HCV to
be highly effective (SVR12 >95%) when given for 12 weeks.

Data has shown that treatment can be shortened when treating recently acquired HCV with
interferon containing treatments. It is not known whether treatment with SOF/VEL can be
shortened.

This study aims to find out if treatment for 6 weeks with open-label SOF/VEL is equivalent to
treatment for 12 weeks with SOF/VEL in participants with recently acquired hepatitis C
infection. The project is a randomised study where both participants and investigators would
not find out the treatment duration of the participants until week 6 of treatment.
Trial website
https://clinicaltrials.gov/show/NCT02625909
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gail V Matthews, MbChB, PhD
Address 0 0
The Kirby Institute, University of New South Wales Australia, Sydney, New South Wales, Australia, NSW 2052
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