ENDURANCE-2: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus (HCV) Genotype 2 Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02640482
• Collaborator: (none)
• Enrollment: 304
• Arms: 3
• Actual Duration (Months): 15

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ABT-493/ABT-530 in adults with genotype 2 chronic hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus (HCV) Infection	Drug: ABT-493/ABT-530; Drug: Placebo for ABT-493/ABT-530	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 304 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 2 Infection (ENDURANCE-2)
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A DB Active Drug ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)	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
Experimental: Arm B DB Placebo Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period)	Drug: Placebo for ABT-493/ABT-530; tablet
Experimental: Arm B OL Active Drug ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)	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) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis [12 weeks after the last actual dose of active 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 active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).

Secondary Outcome Measures

1. Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis [12 weeks after the last actual dose of active study drug]

   SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care).

2. Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures [Up to Week 12 post baseline]

   On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value of 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.

3. Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures [Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24)]

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

4. Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure [12 weeks after the last actual dose of active study drug]

   SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of active study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Screening laboratory result indicating hepatitis C virus (HCV) Genotype-2 (GT2) infection.

• Chronic HCV infection.

• Subject must be HCV treatment-naïve (subject had never received a single dose of any approved or investigational regimen) or had failed prior interferon (IFN) or pegylated-interferon (pegIFN) ± ribavirin (RBV) or sofosbuvir (SOF) + RBV ± pegIFN therapy.

• Subject must be non-cirrhotic.

Exclusion Criteria:

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

• 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.

• 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.

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

• HCV genotype performed during screening indicating coinfection with more than 1 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: NCT02640482
• Other Study ID Numbers: M15-464; 2015-002348-14
• First Posted: Dec 29, 2015
• Last Update Posted: Jul 16, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie: Treatment-Naive; Hepatitis C Virus Genotype 2; Sofosbuvir (SOF)-Experienced; Treatment-Experienced; Non-cirrhotic
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic

Study Results

Participant Flow

Recruitment Details	Safety population: All participants who received at least one dose of study drug.
Pre-assignment Detail	A total of 304 subjects were randomized and 302 subjects received at least 1 dose of study drug.

Arm/Group Title	Arm A DB Active Drug	Arm B DB Placebo Then OL Active Drug
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)	Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period) followed by ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)
Period Title: Overall Study
STARTED	202	100
COMPLETED	199	100
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Arm A DB Active Drug	Arm B DB Placebo Then OL Active Drug	Total
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)	Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period) followed by ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)	Total of all reporting groups
Overall Participants	202	100	302
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.77 (12.79)	57.60 (12.04)	57.04 (12.53)
Sex: Female, Male (Count of Participants)
Female	104 51.5%	55 55%	159 52.6%
Male	98 48.5%	45 45%	143 47.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis
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 active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.

Arm/Group Title	Arm A DB Active Drug
Arm/Group Description	Arm A DB Active Drug: ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
Measure Participants	196
Number [percentage of participants]	99.5 49.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A DB Active Drug
	Comments	Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96% in the Arm A (180 participants) provides >90% power to demonstrate noninferiority of ABT-493/ABT-530 to the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) (95%) (based on the normal approximation of using a single binomial proportion a one-sample test for superiority).
	Type of Statistical Test	Non-Inferiority
	Comments	The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for Arm A as compared with the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 89% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	99.5
	Confidence Interval	(2-Sided) 95%; 98.5 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis
Description	SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care).
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.

Arm/Group Title	Arm A DB Active Drug
Arm/Group Description	Arm A DB Active Drug: ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
Measure Participants	196
Number [percentage of participants]	99.5 49.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A DB Active Drug
	Comments	Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96% in the Arm A (180 participants) provides >90% power to demonstrate superiority of ABT-493/ABT-530 to the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) (95%) (based on the normal approximation of a single binomial proportion using a one-sample test for superiority).
	Type of Statistical Test	Superiority
	Comments	The superiority of the rate of sustained virologic response at 12 weeks after treatment for Arm A as compared with the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 95% to achieve superiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	99.5
	Confidence Interval	(2-Sided) 95%; 98.5 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
Description	On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value of 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	Up to Week 12 post baseline

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.

Arm/Group Title	Arm A DB Active Drug
Arm/Group Description	Arm A DB Active Drug: ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
Measure Participants	196
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

4. Secondary Outcome

Title	Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
Description	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB treatment and 12 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.
Time Frame	Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug in Arm A DB with HCV RNA < LLOQ at the final treatment visit who completed the DB treatment, excluding participants with prior SOF + RBV ± pegIFN failures.

Arm/Group Title	Arm A DB Active Drug
Arm/Group Description	Arm A DB Active Drug: ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
Measure Participants	195
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

5. Secondary Outcome

Title	Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure
Description	SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of active study drug.
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug in Arm A DB with prior SOF + RBV ± pegIFN failures.

Arm/Group Title	Arm A DB Active Drug
Arm/Group Description	Arm A DB Active Drug: ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
Measure Participants	6
Number [percentage of participants]	100 49.5%

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) for all participants in the double-blind (DB) period; TEAEs and TESAEs were also collected from the time of study drug administration until 30 days after the last dose of study drug (up to 16 weeks) for all participants in the open-label (OL) period.
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any AE or SAE with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug (or until prior to the first dose of open-label active drug for subjects who received DB placebo then OL active study drug) and were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	Arm A DB Active Drug		Arm B DB Placebo		Arm B OL Active Drug
Arm/Group Description	ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)		Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period)		ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)
All Cause Mortality
	Arm A DB Active Drug		Arm B DB Placebo		Arm B OL Active Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A DB Active Drug		Arm B DB Placebo		Arm B OL Active Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/202 (1.5%)		1/100 (1%)		1/100 (1%)
Gastrointestinal disorders
Haemorrhoids	1/202 (0.5%)		0/100 (0%)		0/100 (0%)
Hepatobiliary disorders
Bile duct stone	1/202 (0.5%)		0/100 (0%)		0/100 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/202 (0.5%)		0/100 (0%)		0/100 (0%)
Joint dislocation	1/202 (0.5%)		0/100 (0%)		0/100 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/202 (0%)		1/100 (1%)		1/100 (1%)
Other (Not Including Serious) Adverse Events
	Arm A DB Active Drug		Arm B DB Placebo		Arm B OL Active Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/202 (37.1%)		38/100 (38%)		31/100 (31%)
Gastrointestinal disorders
Diarrhoea	20/202 (9.9%)		3/100 (3%)		5/100 (5%)
Nausea	15/202 (7.4%)		4/100 (4%)		8/100 (8%)
General disorders
Asthenia	19/202 (9.4%)		8/100 (8%)		5/100 (5%)
Fatigue	23/202 (11.4%)		10/100 (10%)		5/100 (5%)
Nervous system disorders
Dizziness	6/202 (3%)		5/100 (5%)		1/100 (1%)
Headache	24/202 (11.9%)		12/100 (12%)		8/100 (8%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	4/202 (2%)		5/100 (5%)		1/100 (1%)
Skin and subcutaneous tissue disorders
Pruritus	12/202 (5.9%)		6/100 (6%)		5/100 (5%)
Vascular disorders
Hypertension	2/202 (1%)		5/100 (5%)		2/100 (2%)

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.