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Trial registered on ANZCTR


Registration number
ACTRN12620000794909
Ethics application status
Approved
Date submitted
15/06/2020
Date registered
7/08/2020
Date last updated
7/08/2020
Date data sharing statement initially provided
7/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An efficacy study of combined oral doses of glecaprevir/pibrentasvir and sofosbuvir for 16 weeks in hepatitis C patients with documented NS5A resistance who did not respond to previous treatment
Scientific title
A retreatment study to determine the efficacy of MAVIRET (Glecaprevir/Pibrentasvir) and generic sofosbuvir for 16 weeks in hepatitis C patients with NS5A resistance who did not respond to previous VIEKIRA PAK or MAVIRET or ZEPATIER treatment.
Secondary ID [1] 301506 0
Nil known
Universal Trial Number (UTN)
U1111-1251-7898
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 317838 0
Condition category
Condition code
Infection 315894 315894 0 0
Other infectious diseases
Oral and Gastrointestinal 316211 316211 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
MAVIRET (Glecaprevir 300mg / Pibrentasvir 120mg) and generic sofosbuvir 400mg once daily, oral for 16 weeks.
Mode of administration is oral capsule.
Adherence will be monitored at wk 4, wk 8, wk 12 and wk 16 visits when pills are returned for compliance assessment.
Intervention code [1] 317812 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324106 0
Proportion of subjects who commence retreatment with Maviret and sofosbuvir (intention-to-treat [ITT] and per-protocol [PP] population) who achieve sustained virological response. This is defined as HCV RNA below the lower limit of quantitation (target not detected or target detected, not quantifiable). Presence of HCV RNA in blood sample will be assessed by running Polymerase Chain Reaction using primers that are specifically designed to bind to the HCV.
Timepoint [1] 324106 0
Sample for HCV RNA detection will be collected at a single time point that is greater than or equal to (=) 12 weeks following last dose of treatment. When the result is HCV RNA negative then the patient will have achieved sustained virologic response (SVR12) and clinically judged as cured from HCV.
Secondary outcome [1] 383773 0
On-treatment adherence: calculated by subtracting the number of missed doses from the total number of doses of scheduled treatment and dividing by the total intended therapy duration. This measures the proportion of doses received from treatment initiation until treatment was discontinued or completed. This will be recorded by the study nurse on a drug tablet return checklist.
Timepoint [1] 383773 0
On treatment Wk4, Wk8, Wk12, Wk16 (End of Treatment).
Secondary outcome [2] 383774 0
Proportion with early treatment discontinuation: Discontinuation of therapy prior to the per-protocol planned end of treatment. Patient will be determined as an early discontinuation following 3 failed attempts to contact patient or if they withdraw consent while they are still on treatment.
Timepoint [2] 383774 0
Between Day 1 to Week 16 (End of Treatment)
Secondary outcome [3] 383775 0
Toxicity: number of participants with AEs that are deemed to be treatment-related by the clinical team at the domicile DHB compared to those with no treatment-related AEs reported. Patients will self-report AEs at visits. There are no mandatory laboratory tests during treatment but they may be performed at Investigator-discretion based on self-reported AEs.
Timepoint [3] 383775 0
AE will be collected at wk 4, 8, 12, 16 (end of treatment) .
Secondary outcome [4] 384553 0
Toxicity: number of participants with SAEs compared to those with no SAEs reported. SAEs may be reported by the patient or through data linkage to medical records or GP.
Timepoint [4] 384553 0
SAE reporting Day 1 to Wk 16 (End of Treatment)

Eligibility
Key inclusion criteria
- Confirmed prior treatment with VIEKIRA PAK or MAVIRET or ZEPATIER
- Confirmed failure of VIEKIRA PAK or MAVIRET or ZEPATIER as demonstrated by positive viral load at greater than or equal to (=) 12 weeks after end of treatment (SVR12) and no history of continued injecting drug use to suggest reinfection
- Confirmed NS5A resistance demonstrated
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Severe hepatic impairment classed as Child-Pugh C decompensated cirrhosis. Patients with moderate hepatic impairment classed as Child-Pugh B decompensated cirrhosis will be considered on a case-by-case basis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics
- Proportion of patients achieving sustained virologic response (Intention-to-Treat and Per-Protocol)
- Adherence %
- Early discontinuation %
- Toxicity (descriptive and % Serious Adverse Events and Adverse Events)
- Descriptive analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/09/2020
Actual
Date of last participant enrolment
Anticipated
30/11/2021
Actual
Date of last data collection
Anticipated
30/06/2022
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment outside Australia
Country [1] 22672 0
New Zealand
State/province [1] 22672 0
Auckland

Funding & Sponsors
Funding source category [1] 305947 0
Hospital
Name [1] 305947 0
Auckland District Health Board
Country [1] 305947 0
New Zealand
Primary sponsor type
Hospital
Name
Auckland District Health Board
Address
2 Park Road
Grafton
Auckland
1023
Country
New Zealand
Secondary sponsor category [1] 306407 0
None
Name [1] 306407 0
Address [1] 306407 0
Country [1] 306407 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306190 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 306190 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 306190 0
New Zealand
Date submitted for ethics approval [1] 306190 0
17/03/2020
Approval date [1] 306190 0
10/07/2020
Ethics approval number [1] 306190 0

Summary
Brief summary
Direct Acting Antivirals (DAAs) target specific steps in the Hepatitis C (HCV) life cycle and they are most effective when delivered as combination therapies. Cure rates are high for the DAAs funded in New Zealand (95% for VIEKIRA PAK and 98% for MAVIRET).
For those who did not respond to these treatments, approximately half will have developed dual resistance to NS5A inhibitors and protease inhibitors. The only appropriate retreatment for these patients who did not respond to prior treatment and have NS5A resistance is with a triple DAA combination comprising of sofosbuvir plus an NS5A inhibitor plus a protease inhibitor. In this study, a regimen with 16 week generic sofosburvir + MAVIRET will be tested to see if it can achieve sustained virologic response in treatment experienced patients with NS5A resistance. Previous Phase II and III studies in other countries have demonstrated >95% cure rates following this regimen.
Most participants will be recruited via the doctor or nurse that managed their first (unsuccessful) treatment. The study will involve one screening visit at the participant’s local hospital or clinic during which the participant will consent, have safety blood and other tests to assess eligibility. For example, additional blood tests for NS5A resistance or amount of HCV RNA if not tested previously or the extent of scar tissue in the liver.
Once confirmed eligible, MAVIRET will be prescribed via Pharmac and dispensed from a local pharmacy. Generic sofosbuvir will be couriered from Auckland City Hospital to participant’s homes. Participants will attend four weekly visits during treatment where adverse events, concomitant medication and compliance will be reviewed. 12 weeks after the last dose, HCV RNA viral load will be tested to determine if the patient has been cured.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103026 0
Prof Ed Gane
Address 103026 0
Level 15, Building 1
Auckland District Health Board
2 Park Road
Grafton
Auckland
1023
Country 103026 0
New Zealand
Phone 103026 0
+64 9 307 4949
Fax 103026 0
Email 103026 0
[email protected]
Contact person for public queries
Name 103027 0
Ed Gane
Address 103027 0
Level 15, Building 1
Auckland District Health Board
2 Park Road
Grafton
Auckland
1023
Country 103027 0
New Zealand
Phone 103027 0
+64 9 307 4949
Fax 103027 0
Email 103027 0
[email protected]
Contact person for scientific queries
Name 103028 0
Ed Gane
Address 103028 0
Level 15, Building 1
Auckland District Health Board
2 Park Road
Grafton
Auckland
1023
Country 103028 0
New Zealand
Phone 103028 0
+64 9 307 4949
Fax 103028 0
Email 103028 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No budget allocated to prepare the dataset for IPD.


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.