A Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults in Brazil With Chronic Hepatitis C Virus (HCV) Genotype 1 - 6 Infection
Study Details
Study Description
Brief Summary
This was a Phase 3, open-label, multicenter study to evaluate the efficacy and safety of glecaprevir (GLE)/pibrentasvir (PIB) for an 8 or 12-week treatment duration in adults in Brazil with chronic hepatitis C virus (HCV) genotype (GT) 1 to GT6 infection, without cirrhosis or with compensated cirrhosis, who were HCV treatment-naïve.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This was a Phase 3, open-label, multicenter study to evaluate the efficacy and safety of GLE/PIB for an 8- or 12-week treatment duration in adults in Brazil with chronic HCV GT1 to GT6 infection, without cirrhosis or with compensated cirrhosis with a METAVIR System Fibrosis Score of F2 to F3 (without cirrhosis) or F4 (with compensated cirrhosis) or equivalent, who were HCV treatment-naïve.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 weeks Arm A: Hepatitis C virus (HCV) genotype (GT) 1 to GT6 participants without cirrhosis (fibrosis stage F2 to F3) received glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. |
Drug: Glecaprevir/Pibrentasvir
Film-coated tablet
Other Names:
|
| Experimental: Arm B: GLE/PIB for 12 Weeks Arm B: HCV GT1 to GT6 participants with compensated cirrhosis (F4) received GLE/PIB 300 mg/120 mg QD for 12 weeks. |
Drug: Glecaprevir/Pibrentasvir
Film-coated tablet
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after last dose of study drug (week 20 or 24 depending on treatment regimen)]
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.
Secondary Outcome Measures
- Percentage of Participants With On-treatment HCV Virologic Failure [8 or 12 weeks (depending on treatment regimen)]
On-treatment HCV virologic failure was defined as one of the following: Confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ 100 IU/mL after HCV RNA < 15 IU/mL at any time point during treatment; or Confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) during study drug treatment; or HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment.
- Percentage of Participants With Post-treatment HCV Virologic Relapse [From the end of treatment (8 or 12 weeks depending on treatment regimen) through 12 weeks after the last dose of study drug]
Post-treatment HCV virologic relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA levels < 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant had positive plasma hepatitis C virus (HCV) antibody and HCV ribonucleic acid (RNA) viral load greater than or equal to 1000 IU/mL at Screening Visit.
-
Participant must have been documented as without cirrhosis with METAVIR equivalent fibrosis stage of F2 to F3 or with compensated cirrhosis (F4) based on results of a liver biopsy, or FibroScan, or FibroTest score.
-
Participants who were known to be HCV/Human Immunodeficiency Virus (HIV) co-infected may have been enrolled if they had a positive test result for anti-HIV antibody at Screening and were: naïve to treatment with any antiretroviral therapy (ART), or on a stable, qualifying HIV ART regimen for at least 8 weeks prior to Baseline.
-
Participants with compensated cirrhosis only: Absence of hepatocellular carcinoma (HCC) within 3 months prior to Screening or a negative ultrasound at Screening.
Exclusion Criteria:
-
Current hepatitis B virus (HBV) infection on screening tests.
-
Any current or past clinical evidence of Child-Pugh B or C classification (score of >
- or clinical history of liver decompensation including ascites on physical exam, including hepatic encephalopathy or variceal bleeding.
- Receipt of any investigational or commercially available anti-HCV agents.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitário Cassiano Antônio Moraes - HCUFES /ID# 163512 | Vitoria | Espirito Santo | Brazil | 29 043-260 |
| 2 | Hospital Universitario da Universidade Federal do Maranhao - CEPEC /ID# 163169 | São Luís | Maranhao | Brazil | 65045-040 |
| 3 | Universidade Estadual de Maringá /ID# 166436 | Maringá | Parana | Brazil | 87083-068 |
| 4 | Hospital de Clinicas de Porto Alegre /ID# 163166 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 5 | Hospital de Clinicas de Porto Alegre /ID# 163167 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 6 | Hospital Ernesto Dornelles /ID# 163171 | Porto Alegre | Rio Grande Do Sul | Brazil | 90160-093 |
| 7 | Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu /ID# 163066 | Botucatu | Sao Paulo | Brazil | 18618-686 |
| 8 | Instituto de Infectologia Campinas /ID# 163175 | Campinas | Sao Paulo | Brazil | 13015-080 |
| 9 | Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP /ID# 163054 | Ribeirão Preto | Sao Paulo | Brazil | 14048-900 |
| 10 | Instituto de Infectologia Emilio Ribas /ID# 163170 | São Paulo | Sao Paulo | Brazil | 01246-900 |
| 11 | Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC /ID# 163168 | São Paulo | Sao Paulo | Brazil | 05403-000 |
| 12 | UNIFESP/Unidade de Atendimento Pesquisa Clínica 1 /ID# 164188 | Sao Paulo | Brazil | 04037-003 | |
| 13 | Centro de Referência e Treinamento DST/AIDS /ID# 163174 | Sao Paulo | Brazil | 04121-000 | |
| 14 | Hospital Heliopolis /ID# 163063 | Sao Paulo | Brazil | 04231-030 |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Publications
None provided.- M16-156
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 100 participants were enrolled and received ≥ 1 dose of study drug. |
| Arm/Group Title | Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Arm B: GLE/PIB for 12 Weeks |
|---|---|---|
| Arm/Group Description | Arm A: Hepatitis C virus (HCV) genotype (GT) 1 to GT6 participants without cirrhosis (fibrosis stage F2 to F3) received glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. | Arm B: HCV GT1 to GT6 participants with compensated cirrhosis (F4) received GLE/PIB 300 mg/120 mg QD for 12 weeks. |
| Period Title: Overall Study | ||
| STARTED | 75 | 25 |
| COMPLETED | 75 | 24 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Arm B: GLE/PIB for 12 Weeks | Total |
|---|---|---|---|
| Arm/Group Description | Arm A: Hepatitis C virus (HCV) genotype (GT) 1 to GT6 participants without cirrhosis (fibrosis stage F2 to F3) received glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. | Arm B: HCV GT1 to GT6 participants with compensated cirrhosis (F4) received GLE/PIB 300 mg/120 mg once daily (QD) for 12 weeks. | Total of all reporting groups |
| Overall Participants | 75 | 25 | 100 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.87
(11.28)
|
56.44
(9.62)
|
54.51
(10.90)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
31
41.3%
|
5
20%
|
36
36%
|
| Male |
44
58.7%
|
20
80%
|
64
64%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
46
61.3%
|
17
68%
|
63
63%
|
| Black or African American |
22
29.3%
|
4
16%
|
26
26%
|
| Asian |
1
1.3%
|
1
4%
|
2
2%
|
| Multi-race |
6
8%
|
3
12%
|
9
9%
|
Outcome Measures
| Title | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) |
|---|---|
| Description | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug. |
| Time Frame | 12 weeks after last dose of study drug (week 20 or 24 depending on treatment regimen) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders. Data are reported for the overall study population according to the prespecified analysis plan for this study. |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 or 12 weeks |
| Measure Participants | 100 |
| Number (95% Confidence Interval) [percentage of participants] |
98.0
130.7%
|
| Title | Percentage of Participants With On-treatment HCV Virologic Failure |
|---|---|
| Description | On-treatment HCV virologic failure was defined as one of the following: Confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ 100 IU/mL after HCV RNA < 15 IU/mL at any time point during treatment; or Confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) during study drug treatment; or HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment. |
| Time Frame | 8 or 12 weeks (depending on treatment regimen) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least 1 dose of study drug. Data are reported for the overall study population according to the prespecified analysis plan for this study. |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | GLE/PIB for 8 or 12 weeks |
| Measure Participants | 100 |
| Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
| Title | Percentage of Participants With Post-treatment HCV Virologic Relapse |
|---|---|
| Description | Post-treatment HCV virologic relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA levels < 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed. |
| Time Frame | From the end of treatment (8 or 12 weeks depending on treatment regimen) through 12 weeks after the last dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least 1 dose of study drug and who completed treatment, had HCV RNA < 15 IU/mL at final treatment visit, and had at least one post-treatment HCV RNA value. Data are reported for the overall study population according to the prespecified analysis plan for this study. |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | GLE/PIB for 8 or 12 weeks |
| Measure Participants | 100 |
| Number (95% Confidence Interval) [percentage of participants] |
1.0
1.3%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug. | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events are reported for the overall study population according to the prespecified analysis plan for this study. | |
| Arm/Group Title | All Participants | |
| Arm/Group Description | All enrolled participants who received at least one dose of study drug. | |
All Cause Mortality |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/100 (0%) | |
Serious Adverse Events |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/100 (4%) | |
| Blood and lymphatic system disorders | ||
| IRON DEFICIENCY ANAEMIA | 1/100 (1%) | 1 |
| Gastrointestinal disorders | ||
| ABDOMINAL PAIN | 1/100 (1%) | 1 |
| GASTRIC ULCER | 1/100 (1%) | 1 |
| Infections and infestations | ||
| DIARRHOEA INFECTIOUS | 1/100 (1%) | 1 |
| Injury, poisoning and procedural complications | ||
| TRANSFUSION REACTION | 1/100 (1%) | 1 |
| Renal and urinary disorders | ||
| ACUTE KIDNEY INJURY | 1/100 (1%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 30/100 (30%) | |
| Gastrointestinal disorders | ||
| NAUSEA | 6/100 (6%) | 6 |
| General disorders | ||
| FATIGUE | 5/100 (5%) | 5 |
| Nervous system disorders | ||
| HEADACHE | 18/100 (18%) | 18 |
| Skin and subcutaneous tissue disorders | ||
| PRURITUS | 7/100 (7%) | 7 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
- M16-156