Trial Outcomes & Findings for Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection (NCT NCT04042740)

Last Updated: 2024-07-11

Results Overview

SVR12 defined as 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 (Week 16). If a participant did not have HCV RNA measurement at Week 16, the participant was considered as SVR12 failure, unless there were preceding and subsequent HCV RNA measurements that were both LLOQ (either TD or TND).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Week 16 (12 weeks post study treatment)

Results posted on

2024-07-11

Participant Flow

Participants were enrolled from November 2019 to January 2023.

Participant milestones

Participant milestones
Measure	Glecaprevir/Pibrentasvir (G/P) Followed by Re-treatment, as Needed G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1). Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia were offered re-treatment (8-16 weeks), followed by 24 weeks of observation (Step 2).
Step 1 (4-week G/P + 24-week Follow-up) STARTED	45
Step 1 (4-week G/P + 24-week Follow-up) Initiated Study Treatment	45
Step 1 (4-week G/P + 24-week Follow-up) Completed 16 Weeks	44
Step 1 (4-week G/P + 24-week Follow-up) COMPLETED	42
Step 1 (4-week G/P + 24-week Follow-up) NOT COMPLETED	3
Step 2 (HCV Re-treatment) STARTED	4
Step 2 (HCV Re-treatment) COMPLETED	3
Step 2 (HCV Re-treatment) NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Glecaprevir/Pibrentasvir (G/P) Followed by Re-treatment, as Needed G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1). Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia were offered re-treatment (8-16 weeks), followed by 24 weeks of observation (Step 2).
Step 1 (4-week G/P + 24-week Follow-up) Lost to Follow-up	2
Step 1 (4-week G/P + 24-week Follow-up) Withdrawal by Subject	1

Baseline Characteristics

Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Age, Continuous	36 years n=93 Participants
Sex/Gender, Customized Female	1 Participants n=93 Participants
Sex/Gender, Customized Male	43 Participants n=93 Participants
Sex/Gender, Customized Non-binary	1 Participants n=93 Participants
Sex: Female, Male Female	1 Participants n=93 Participants
Sex: Female, Male Male	44 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Race/Ethnicity, Customized Asian	3 Participants n=93 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=93 Participants
Race/Ethnicity, Customized White	23 Participants n=93 Participants
Race/Ethnicity, Customized Other	4 Participants n=93 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=93 Participants
Region of Enrollment United States	31 Participants n=93 Participants
Region of Enrollment Brazil	14 Participants n=93 Participants
HCV history No history of HCV	38 Participants n=93 Participants
HCV history Previous HCV	7 Participants n=93 Participants
HCV genotype Genotype 1	32 Participants n=93 Participants
HCV genotype Genotype 2	2 Participants n=93 Participants
HCV genotype Genotype 3	1 Participants n=93 Participants
HCV genotype Genotype 4	5 Participants n=93 Participants
HCV genotype Indeterminate	1 Participants n=93 Participants
HCV genotype Not detected	3 Participants n=93 Participants
HCV genotype Unable to result	1 Participants n=93 Participants
HCV RNA	5.25 log10 IU/mL n=93 Participants
HIV-1 status HIV-1 present	23 Participants n=93 Participants
HIV-1 status No HIV-1	22 Participants n=93 Participants
Injection drug use Former	12 Participants n=93 Participants
Injection drug use Never	33 Participants n=93 Participants

PRIMARY outcome

Timeframe: Week 16 (12 weeks post study treatment)

Population: All eligible participants who initiated study treatment

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment Discontinuation (SVR12)	84.4 percentage of participants Interval 73.6 to 91.3

PRIMARY outcome

Timeframe: From study entry to Week 8 (4 weeks post study treatment)

Population: All eligible participants who initiated study treatment

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 serious AE (SAE) or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) were used.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Percentage of Participants Who Experienced Adverse Events (AEs)	60.0 percentage of participants Interval 45.5 to 73.0

PRIMARY outcome

Timeframe: From study entry to Week 4

Population: All eligible participants who initiated study treatment

Number of participants who completed 4 weeks of treatment without discontinuation due to AEs

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Number of Participants Who Completed 4 Weeks of Treatment Without Discontinuation Due to AEs	45 Participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 4, 8, 12, 28

Population: All eligible participants who initiated study treatment with HCV RNA data available at the given visit. The study conduct overlapped with the COVID-19 pandemic. At the beginning of the COVID-19 pandemic, Week 16 visit was prioritized; other study visits may have occurred remotely without HCV RNA collection, due to COVID-related restrictions at the sites.

Percentage of participants with HCV RNA less than LLOQ (TD or TND). Given the substantial amount of missing data due to the SARS-CoV-2 pandemic, the planned analysis of 90% confidence intervals for the percentage of participants with HCV RNA \<LLOQ at study visits could not be conducted in a meaningful way.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Percentage of Participants With HCV RNA Less Than LLOQ Week 1 HCV RNA <LLOQ	51.4 percentage of participants
Percentage of Participants With HCV RNA Less Than LLOQ Week 2 HCV RNA <LLOQ	70.7 percentage of participants
Percentage of Participants With HCV RNA Less Than LLOQ Week 4 HCV RNA <LLOQ	97.6 percentage of participants
Percentage of Participants With HCV RNA Less Than LLOQ Week 8 HCV RNA <LLOQ	97.2 percentage of participants
Percentage of Participants With HCV RNA Less Than LLOQ Week 12 HCV RNA <LLOQ	88.2 percentage of participants
Percentage of Participants With HCV RNA Less Than LLOQ Week 28 HCV RNA <LLOQ	81.0 percentage of participants

SECONDARY outcome

Timeframe: From Week 1 to Week 16

Population: All eligible participants who initiated study treatment

Virologic failure defined as failure to achieve unquantifiable HCV RNA or confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Number of Participants With HCV Virologic Failure	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Step 2 entry (median time of Step 2 entry was at 21 weeks after study entry.

Population: All participants who entered Step 2 for HCV re-treatment.

Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia in Step 1 were offered to enter Step 2 for re-treatment. HCV re-treatment regimens may have included various regimens including study-provided G/P and alternate regimens through clinical care. This outcome measure is used to report the re-treatment regimens observed in Step 2.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir (G/P) n=4 Participants G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).
Number of Participants by HCV Re-Treatment Regimen in Step 2 Glecaprevir/pibrentasvir	3 Participants
Number of Participants by HCV Re-Treatment Regimen in Step 2 Sofosbuvir/velpatasvir/voxilaprevir	1 Participants

Adverse Events

Glecaprevir/Pibrentasvir (G/P)

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

HCV Re-Treatment Regimens

Serious events: 1 serious events

Other events: 4 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Glecaprevir/Pibrentasvir (G/P) n=45 participants at risk G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1).	HCV Re-Treatment Regimens n=4 participants at risk Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia in Step 1 were offered to enter Step 2 for re-treatment. HCV re-treatment regimens may have included G/P FDC tablets orally once daily for 8-16 weeks, or alternate regimens through clinical care.
Injury, poisoning and procedural complications Overdose	2.2% 1/45 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.	0.00% 0/4 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.
Nervous system disorders Carotid artery disease	2.2% 1/45 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.	0.00% 0/4 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.
Psychiatric disorders Anxiety	2.2% 1/45 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.	0.00% 0/4 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.
Psychiatric disorders Mental status changes	2.2% 1/45 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.	0.00% 0/4 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.
Renal and urinary disorders Haematuria	0.00% 0/45 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.	25.0% 1/4 • Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks). New diagnoses, signs/symptoms and laboratory values that were Grade ≥2, led to a change in study treatment regardless of grade or met SAE definition or EAE reporting requirements, regardless of attribution to study treatment. DAIDS AE Grading Table (V2.1) and EAE Manual (V1.0) were used. All eligible participants who initiated study treatment are included. For the subset who continued to Step 2 for HCV re-treatment, the AEs that occurred in Step 2 are shown in a separate column.

Other adverse events

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

Phone: (301) 628-3348

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER