PURGE-C: Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy of a fixed dose combination (FDC) of glecaprevir/pibrentasvir (G/P) given for 4 weeks in acute hepatitis C (HCV)-infected participants, with or without HIV-1 coinfection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study will be conducted in two steps. In Step 1, participants will receive four weeks of treatment with G/P for acute HCV infection and then followed 24 weeks post treatment. Participants with HCV recurrence (reinfection, suspected relapse or undefined post-treatment viremia) or HCV virologic failure before or at the Step 1 Week 16/SVR12 (sustained virologic response 12 weeks post-treatment) visit may enter Step 2 for re-treatment. The remaining participants complete the study at Week 28 of Step 1. The study primary and secondary outcome measures pertain to Step 1.
In Step 2, participants will be re-treated with G/P with or without ribavirin (RBV) for up to 16 weeks, and followed for 24 weeks post treatment. Post-treatment follow-up for Step 2 will include visits for SVR12 determination after re-treatment.
In Step 1, study visits are scheduled at study entry, weeks 1 and 2 (on-treatment), week 4 (treatment discontinuation), and weeks 8, 12, 16 and 28 (post-treatment follow-up). In Step 2, participants will have study visits during the re-treatment period, where the number of visits depends on the re-treatment, and visits at 12 and 24 weeks post treatment. Study visits may include physical examinations, clinical assessments, blood and urine collection, questionnaires, and HCV re-infection prevention counseling.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Glecaprevir/Pibrentasvir (G/P) In Step 1, participants will receive G/P FDC tablets to be taken orally once daily for 4 weeks. Any participant who experiences viral re-infection, suspected relapse, virologic failure, or undefined post-treatment HCV viremia may enter Step 2. In Step 2, participants may receive G/P FDC tablets orally once daily for 8-16 weeks. Some participants may also receive ribavirin (RBV) tablets orally twice daily. Alternate regimens are allowed in Step 2. |
Drug: Glecaprevir/Pibrentasvir (G/P)
Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.
Drug: Ribavirin (RBV)
Tablets containing 200 mg of ribavirin. RBV dosed according to weight-based and renal dosing tables in study protocol.
|
Outcome Measures
Primary Outcome Measures
- Proportion of participants with sustained virologic response at 12 weeks post-treatment (SVR12) [Week 16 (12 weeks post treatment)]
SVR12 defined as achieving unquantifiable HCV RNA (less than the lower limit of quantification [LLOQ] target detected [TD] or target not detected [TND]) at study visit 12 weeks post treatment. If a participant does not have any HCV RNA measurements in this time period then the participant will be considered as SVR12 failure, unless there are preceding and subsequent HCV RNA measurements that are both LLOQ (either TD or TND).
- Proportion of participants who experienced adverse events (AEs) [From study treatment initiation to 4 weeks after study treatment discontinuation (Week 8)]
Study protocol required reporting of (1) AEs Grade greater than or equal to 2, (2) AEs that led to a change in study treatment regardless of grade and (3) AEs meeting ICH definition of SAE or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) are used.
- Number of participants who complete 4 weeks of treatment without discontinuation due to AEs [From study entry to Week 4]
Number of participants who complete 4 weeks of treatment without discontinuation due to AEs
Secondary Outcome Measures
- Proportion of participants with HCV RNA less than LLOQ [Weeks 1, 2, 4, 8, 12, 28]
Proportion of participants with HCV RNA less than LLOQ (TD or TND)
- Number of participants with HCV virologic failure [Weeks 1, 2, 4]
Virologic failure defined as failure to achieve unquantifiable HCV RNA and confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir
Eligibility Criteria
Criteria
Inclusion Criteria
-
Acute HCV infection (or reinfection) within 24 weeks prior to entry.
-
Detectable HCV RNA at the screening visit.
Exclusion Criteria
-
Any HCV treatment during the current acute HCV infection episode.
-
Known preexisting cirrhosis
-
Acute HIV-1 infection
-
Presence of active or acute AIDS-defining opportunistic infections, active serious infection (other than HIV-1 or HCV), active hepatitis B virus (HBV) or active hepatitis A virus (HAV)
-
Chronic use of systemically administered immunosuppressive agents
-
History of solid organ transplantation.
-
History of conditions that could interfere with the absorption of the study drug.
-
Concurrent use of prohibited medications
-
Known hypersensitivity to glecaprevir or pibrentasvir, the metabolites, or parts of the formulation.
-
Females who are pregnant or breastfeeding
-
Males with pregnant female partner.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ucsd, Avrc Crs (701) | San Diego | California | United States | 92103 |
| 2 | University of Colorado Hospital CRS (6101) | Aurora | Colorado | United States | 80045 |
| 3 | Whitman-Walker Institute, Inc. CRS (31791) | Washington | District of Columbia | United States | 20005 |
| 4 | The Ponce de Leon Center CRS (5802) | Atlanta | Georgia | United States | 30308 |
| 5 | Johns Hopkins Adult AIDS CRS | Baltimore | Maryland | United States | 21287 |
| 6 | Massachusetts General Hospital ACTG CRS (101) | Boston | Massachusetts | United States | 02114 |
| 7 | Weill Cornell Chelsea CRS (7804) | New York | New York | United States | 10010 |
| 8 | Columbia Physicians and Surgeons CRS (30329) | New York | New York | United States | 10032 |
| 9 | Weill Cornell Upton CRS (7803) | New York | New York | United States | 10065 |
| 10 | Unc Aids Crs (3201) | Chapel Hill | North Carolina | United States | 27514 |
| 11 | Greensboro CRS (3203) | Greensboro | North Carolina | United States | 27401 |
| 12 | The Miriam Hosp. ACTG CRS (2951) | Providence | Rhode Island | United States | 02906 |
| 13 | Trinity Health and Wellness Center CRS | Dallas | Texas | United States | 75208 |
| 14 | University of Washington AIDS CRS (1401) | Seattle | Washington | United States | 98104 |
| 15 | Instituto de Pesquisa Clinica Evandro Chagas (12101) | Rio de Janeiro | Brazil | 21045 | |
| 16 | Puerto Rico-AIDS CRS (5401) | San Juan | Puerto Rico | 00931 |
Sponsors and Collaborators
- AIDS Clinical Trials Group
- AbbVie
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Arthur Y. Kim, MD, Massachusetts General Hospital (MGH) CRS
- Study Chair: Susanna Naggie, MD, MHS, Duke University Medical Center CRS
- Study Chair: David Wyles, MD, University of Colorado Hospital CRS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACTG A5380
- 38553
- UM1AI068636