The purpose of this study is to evaluate how effective, safe and tolerable Sofosbuvir (SOF)/Velpatasvir(VEL) is when taken by people with recent hepatitis C virus (HCV) infection, in particular whether the length of treatment can be shortened. Study participants will be randomly (occur by chance) assigned into one of the two different groups. The short treatment duration group will receive SOF/VEL for 6 weeks and the standard treatment duration group will receive SOF/VEL for 12 weeks.

Phase 1

• Conditions: Recent hepatitis C virus infection all genotypes.; MedDRA version: 20.0Level: PTClassification code 10019744Term: Hepatitis CSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2015-004243-39-NL
• Lead Sponsor: niversity of New South Wales Australia

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-11-08
• Last Update Posted: 9 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

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) Negative pregnancy test at baseline (females of childbearing potential only)
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
8) Medically stable on the basis of physical examination, medical history and vital signs
9) Adequate literacy 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 6 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 6 months
and
ii) Acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the previous 12 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 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:
oNucleos(t)ide reverse transcriptase inhibitors: Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), emtricitabine (FTC)Non-nucleoside reverse transcriptase inhibitors: Rilpivirine
oProtease inhibitors: Atazanavir, darunavir, lopinavir, ritonavir
oIntegrase inhibitors: Dolutegravir, raltegravir, elvitegravir/cobicistat
•Contraindicated ARV include:
oEfavirenz
?50% reduction in velpatasvir (GS-5816) exposure
oDidanosine
oZidovudine
oTipranavir
Other ARV agents may be permissible at the time of study commencement pending further drug-drug interaction studies; please discuss with the Medical Monitor.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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:
a. 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.
b. 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
c. Solid organ transplant
d. 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.
e. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
2) Subject has a known or documented prior history of cirrhosis
3) 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
4) Any of the following lab parameters at screening:
a. Direct bilirubin > 1.5 x ULN
b. Platelets < 50,000/µL
c. Creatinine clearance (CLcr) < 50 mL/min
d. Haemoglobin < 10 g/dL
e. Albumin < 30g/L
f. International Normalised Ratio (INR) >1.5 (unless subject is on a stable anticoagulant regimen or has known coagulopathy
5) Pregnant or nursing female.
6) Use of prohibited concomitant medications as described in protoocl section 5.2
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 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

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified