The Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 4, 5, or 6 Infection (ENDURANCE-4)

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02636595
• Collaborator: (none)
• Enrollment: 121
• Arm: 1
• Actual Duration (Months): 14

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of response to treatment by evaluating the percentage of subjects achieving a 12-week sustained virologic response (SVR12) after 12 weeks of treatment with ABT-493/ABT-530 and to evaluate the safety of the regimen in participants with chronic hepatitis C virus (HCV) genotype (GT) 4, 5, or 6 infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus	Drug: ABT-493/ABT-530	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 4, 5, or 6 Infection (ENDURANCE-4)
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-493/ABT-530 ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.	Drug: ABT-493/ABT-530; Tablet; ABT-493 coformulated with ABT-530; Other Names: ABT-493 also known as glecaprevir ABT-530 also known as pibrentasvir MAVYRET

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last actual dose of study drug]

   SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.

Secondary Outcome Measures

1. Percentage of Participants With On-treatment Virologic Failure [Treatment weeks 1, 2, 4, 8, and 12 (end of treatment) or premature discontinuation from treatment]

   On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.

2. Percentage of Participants With Post-treatment Relapse [From the end of treatment through 12 weeks after the last dose of study drug]

   Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Screening laboratory result indicating hepatitis C virus (HCV) genotype (GT) 4, 5, or 6 infection.

2. Chronic HCV infection.

3. HCV treatment-naïve or treatment experienced (interferon [IFN] or pegylated interferon [pegIFN] with or without ribavirin [RBV]; sofosbuvir [SOF] plus RBV with or without pegIFN).

4. Non-cirrhotic participants.

Exclusion Criteria:

1. History of severe, life-threatening or other significant sensitivity to any excipient of the study drugs.

2. Female who is pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study.

3. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator.

4. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).

5. Co-infection with more than one HCV genotype.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, Colombo M, Calinas F, Aguilar H, de Ledinghen V, Mantry PS, Hezode C, Marinho RT, Agarwal K, Nevens F, Elkhashab M, Kort J, Liu R, Ng TI, Krishnan P, Lin CW, Mensa FJ. Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis. Clin Gastroenterol Hepatol. 2018 Mar;16(3):417-426. doi: 10.1016/j.cgh.2017.09.027. Epub 2017 Sep 22.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02636595
• Other Study ID Numbers: M13-583; 2015-002349-80
• First Posted: Dec 22, 2015
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie: Hepatitis C Genotype 4; Hepatitis C; Chronic Hepatitis C; Hepatitis C Genotype 6; Hepatitis C Genotype 5
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic

Study Results

Participant Flow

Pre-assignment Detail	This study included a 35-day screening period.

Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Period Title: Overall Study
STARTED	121
COMPLETED	119
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Overall Participants	121
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.66 (10.95)
Sex: Female, Male (Count of Participants)
Female	44 36.4%
Male	77 63.6%

Outcome Measures

1. Primary Outcome

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]) 12 weeks after the last dose of study drug.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were imputed as nonresponders.

Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	121
Number (95% Confidence Interval) [percentage of participants]	99.2 82%

2. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
Time Frame	Treatment weeks 1, 2, 4, 8, and 12 (end of treatment) or premature discontinuation from treatment

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population).

Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	121
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Post-treatment Relapse
Description	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.
Time Frame	From the end of treatment through 12 weeks after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA <LLOQ at the final treatment visit.

Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	118
Number (95% Confidence Interval) [percentage of participants]	0 0%

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 16 weeks).
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any AE or SAE with an onset date after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	ABT-493/ABT-530
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
All Cause Mortality
	ABT-493/ABT-530
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ABT-493/ABT-530
	Affected / at Risk (%)	# Events
Total	1/121 (0.8%)
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK	1/121 (0.8%)
Other (Not Including Serious) Adverse Events
	ABT-493/ABT-530
	Affected / at Risk (%)	# Events
Total	59/121 (48.8%)
Gastrointestinal disorders
DIARRHOEA	8/121 (6.6%)
NAUSEA	12/121 (9.9%)
General disorders
ASTHENIA	11/121 (9.1%)
FATIGUE	21/121 (17.4%)
Nervous system disorders
HEADACHE	25/121 (20.7%)
Skin and subcutaneous tissue disorders
PRURITUS	9/121 (7.4%)

Limitations/Caveats

[Not Specified]

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.