A Study to Evaluate the Safety and Efficacy of ABT-493/ABT-530 in Adult Post-Liver or Post-Renal Transplant Recipients With Chronic Hepatitis C Virus (MAGELLAN-2)

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02692703
• Collaborator: (none)
• Enrollment: 100
• Arm: 1
• Actual Duration (Months): 14.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of 12 weeks of treatment of ABT-493/ABT-530 (glecaprevir/pibrentasvir) in adults who are post primary orthotopic liver or renal transplant with chronic hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C; HCV; Hepatitis C Virus	Drug: glecaprevir/pibrentasvir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of ABT-493/ABT-530 in Adult Post-Liver or Post-Renal Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 - 6 Infection (MAGELLAN-2)
• Actual Study Start Date: Apr 22, 2016
• Actual Primary Completion Date: Apr 13, 2017
• Actual Study Completion Date: Jun 29, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last dose of study drug (up to 24 weeks)]

   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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 compared with the historical SVR12 rate for the current standard of care regimens (sofosbuvir [SOF]/ledipasvir [LDV] + ribavirin [RBV] OR SOF + daclatasvir [DCV] + RBV). Participants with missing data after backward imputation were counted as non-responders.

Secondary Outcome Measures

1. Percentage of Participants With On-treatment Virologic Failure [Up to 12 weeks]

   On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in 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 (up to 12 weeks)]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female, at least 18 years of age at time of screening.

• Screening laboratory result indicating hepatitis C virus (HCV) genotype 1-6 (GT1-6) infection.

• Subject is a recipient of a cadaveric or living donor liver transplant which was a consequence of HCV infection at least 3 months prior to screening Or subject received a cadaveric or living donor kidney at least 3 months before screening.

• Subjects must be documented as non-cirrhotic.

• Subject is currently taking a stable immunosuppression regimen based on tacrolimus, sirolimus, everolimus, mycophenolate mofetil (MMF), mycophenolic acid, azathioprine, and/or cyclosporine.

Exclusion Criteria:

• Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug.

• Clinical history of fibrosing cholestatic hepatitis post-transplant.

• Re-transplantation of the liver or kidney.

• Steroid resistant rejection of the transplanted liver or kidney, or a history of rejection treated with high dose steroid within 3 months of screening.

• History of post-transplant complications related to hepatic or renal vasculature.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Susan Rhee, MD, AbbVie

Study Documents (Full-Text)

• Study Protocol - Jun 21, 2016
• Statistical Analysis Plan - Oct 27, 2016

More Information

Additional Information:

• Related Info

Publications

• Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, Gane E, Kao JH, Mantry PS, Mutimer D, Reddy KR, Tran TT, Hu YB, Gulati A, Krishnan P, Dumas EO, Porcalla A, Shulman NS, Liu W, Samanta S, Trinh R, Forns X. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection. Hepatology. 2018 Oct;68(4):1298-1307. doi: 10.1002/hep.30046. Epub 2018 Jul 25.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02692703
• Other Study ID Numbers: M13-596; 2015-005616-14
• First Posted: Feb 26, 2016
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by AbbVie: HCV Treatment Experienced; Hepatitis C; HCV Genotype 3; Without cirrhosis; Non-cirrhotic; HCV Genotype 2; Renal Transplant; HCV Treatment Naive; Post transplant; HCV Genotype 6; Liver Transplant; HCV Genotype 5; HCV Genotype 4; Kidney Transplant; HCV Genotype 1
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic

Study Results

Participant Flow

Pre-assignment Detail	The study included a 36-day screening period.

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Period Title: Overall Study
STARTED	100
COMPLETED	98
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Overall Participants	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.19 (7.68)
Sex: Female, Male (Count of Participants)
Female	25 25%
Male	75 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 17%
Not Hispanic or Latino	83 83%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	10 10%
Native Hawaiian or Other Pacific Islander	3 3%
Black or African American	8 8%
White	78 78%
More than one race	1 1%
Unknown or Not Reported	0 0%

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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 compared with the historical SVR12 rate for the current standard of care regimens (sofosbuvir [SOF]/ledipasvir [LDV] + ribavirin [RBV] OR SOF + daclatasvir [DCV] + RBV). Participants with missing data after backward imputation were counted as non-responders.
Time Frame	12 weeks after the last dose of study drug (up to 24 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all participants who received at least 1 dose of study drug.

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	100
Number (95% Confidence Interval) [percentage of participants]	98 98%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glecaprevir/Pibrentasvir
	Comments	Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96%, 90 participants provides >90% power to demonstrate noninferiority of the regimen to the historical rate for current standard of care regimens (SOF/LDV + RBV OR SOF + DCV + RBV) (94%) (based on the normal approximation of a single binomial proportion in 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 as compared with the historical rate for the current standard of care regimens (SOF/LDV + RBV or SOF + DCV + RBV) 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 86% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	98
	Confidence Interval	(2-Sided) 95%; 95.3 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 in 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 12 weeks

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	100
Number [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.
Time Frame	From the end of treatment through 12 weeks after the last dose of study drug (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Measure Participants	99
Number [percentage of participants]	1 1%

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 (up to 16 weeks).
Adverse Event Reporting Description	TEAEs and SAEs are defined as any AE or SAE that begins or worsens in severity after initiation of study drug until 30 days after the last dose of study drug.
Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
All Cause Mortality
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	0/100 (0%)
Serious Adverse Events
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	8/100 (8%)
Blood and lymphatic system disorders
Neutropenia	1/100 (1%)	1
Congenital, familial and genetic disorders
Arteriovenous malformation	1/100 (1%)	1
Infections and infestations
Groin infection	1/100 (1%)	1
Hepatitis E	1/100 (1%)	1
Pneumonia	1/100 (1%)	1
Pyelonephritis	1/100 (1%)	2
Respiratory tract infection	1/100 (1%)	1
Sepsis	2/100 (2%)	3
Sinusitis	1/100 (1%)	1
Urinary tract infection	1/100 (1%)	2
Injury, poisoning and procedural complications
Vascular pseudoaneurysm ruptured	1/100 (1%)	1
Investigations
Immunosuppressant drug level increased	1/100 (1%)	1
Liver function test increased	1/100 (1%)	1
Nervous system disorders
Cerebrovascular accident	1/100 (1%)	1
Renal and urinary disorders
Renal failure	1/100 (1%)	1
Renal impairment	2/100 (2%)	2
Other (Not Including Serious) Adverse Events
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	67/100 (67%)
Gastrointestinal disorders
Abdominal pain upper	5/100 (5%)	5
Diarrhoea	10/100 (10%)	11
Nausea	12/100 (12%)	13
Vomiting	5/100 (5%)	8
General disorders
Fatigue	22/100 (22%)	26
Infections and infestations
Upper respiratory tract infection	8/100 (8%)	10
Urinary tract infection	5/100 (5%)	6
Viral upper respiratory tract infection	8/100 (8%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	7/100 (7%)	7
Pain in extremity	5/100 (5%)	7
Nervous system disorders
Dizziness	6/100 (6%)	7
Headache	22/100 (22%)	26
Psychiatric disorders
Insomnia	6/100 (6%)	6
Respiratory, thoracic and mediastinal disorders
Cough	9/100 (9%)	9
Skin and subcutaneous tissue disorders
Pruritus	12/100 (12%)	13

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.