Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study

Hepatitis C Virus Infection Clinical Trial

— MAGELLAN-3  

Official title:

An Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Combination With Sofosbuvir and Ribavirin in Chronic Hepatitis C (HCV) Infected Subjects Who Have Experienced Virologic Failure in AbbVie HCV Clinical Studies (MAGELLAN-3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02939989
• Other study ID #: M15-942
• Secondary ID: 2016-002491-26
• Status: Completed
• Phase: Phase 3
• Start date: November 21, 2016
• Est. completion date: July 30, 2021

Study information

• Verified date: April 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the efficacy and safety of co-administration of glecaprevir (ABT-493)/pibrentasvir (ABT 530) plus sofosbuvir (SOF) plus ribavirin (RBV) in hepatitis C virus (HCV) genotype (GT) 1 - 6-infected participants (including non-cirrhotic, or cirrhotic with compensated cirrhosis participants) who had experienced virologic failure in an AbbVie parent clinical study.

Description:

This study enrolled HCV infected adults who had experienced virologic failure following treatment with glecaprevir/pibrentasvir or paritaprevir/ritonavir/ombitasvir + dasabuvir (DSV) (3D) or paritaprevir/ritonavir/ombitasvir (2D) regimens in one of the following AbbVie hepatitis C virus parent studies:

• M13-594 (NCT02640157)

• M13-596 (NCT02692703)

• M14-172 (NCT02642432)

• M14-242 (NCT02493855)

• M14-868 (NCT02243293)

• M15-410 (NCT02446717)

• M15-592 (NCT03222583)

• M16-126 (NCT02966795)

• M16-135 (NCT03089944)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 30, 2021
• Est. primary completion date: May 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 99 Years

Eligibility

Inclusion Criteria:

• Male or female subjects must be adults (18 years of age or older) or adolescents (12 to less than 18 years of age weighing at least 35 kg).

• Subject must have experienced virologic failure during or after treatment with ABT-493/ABT-530 in an AbbVie HCV parent study. Subjects who have experienced virologic failure during or after receiving ombitasvir/paritaprevir/r + dasabuvir (3D), or ombitasvir/paritaprevir/r (2D) in an AbbVie HCV parent study may be enrolled at AbbVie's discretion. Treatment in the parent study must have been completed or discontinued at least 1 month prior to the Screening Visit.

• Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements.

• Cirrhotic subjects must have compensated cirrhosis, (Child-Pugh score of = 6) at Screening and no current or past evidence of Child-Pugh B or C Classification or no clinical history of liver decompensation, including ascites noted on physical exam, hepatic encephalopathy or esophageal variceal bleeding.

• Cirrhotic subjects must have absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound (US), computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or a negative US at Screening.

Exclusion Criteria:

• History of severe, life-threatening or other clinically significant sensitivity to any study drug or drug component.

• Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for 4 months after the last dose of study drug, or as directed per the local RBV label, whichever is more restrictive.

• 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).

• Screening laboratory analyses showing calculated creatinine clearance < 30 mL/min.

• Discontinuation from the AbbVie HCV parent study for reasons other than virologic failure (e.g., non-adherence, lost to follow-up, and/or the occurrence of an adverse event).

• Receipt of any HCV treatment after failing the treatment regimen in the AbbVie HCV parent study.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection

Intervention

Drug:
• Sofosbuvir
Tablet for oral administration
• Glecaprevir/Pibrentasvir
Coformulated tablet for oral administration
• Ribavirin
Tablet for oral administration

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital /ID# 200944	Herston	Queensland
Australia	The Royal Melbourne Hospital /ID# 155727	Parkville	Victoria
Canada	University of Calgary /ID# 155726	Calgary	Alberta
China	Beijing Di Tan Hospital, Capital Medical University /ID# 218496	Beijing
China	West China Hospital, Sichuan University /ID# 217613	Chengdu
China	The First Hospital Affiliated to AMU (Southwest Hospital) /ID# 218494	Chongqing
China	Mengchao Hepatobiliary Hospital of Fujian Medical University /ID# 218495	Fuzhou
Germany	Zentru fur HIV und Heaptogastroenterologie /ID# 155592	Düsseldorf	Nordrhein-Westfalen
Germany	Asklepios Klinik St. Georg /ID# 155733	Hamburg
Korea, Republic of	Samsung Medical Center /ID# 214844	Seoul
New Zealand	Auckland City Hospital /ID# 200945	Grafton	Auckland
New Zealand	Waikato Hospital /ID# 155728	Hamilton	Waikato
New Zealand	Dunedin Hospital /ID# 155591	Otago
Russian Federation	Medical Company Hepatolog /ID# 214314	Samara	Samarskaya Oblast
Spain	Hospital Universitario Puerta de Hierro, Majadahonda /ID# 155734	Majadahonda	Madrid
Sweden	Duplicate_Karolinska Univ Sjukhuset /ID# 155735	Solna
Switzerland	Inselspital, Universitätsspital Bern /ID# 155716	Bern
United Kingdom	Duplicate_Imperial College Healthcare NHS Trust /ID# 155718	London
United States	Digestive Disease Associates - Baltimore /ID# 155713	Baltimore	Maryland
United States	University of Buffalo /ID# 155721	Buffalo	New York
United States	Henry Ford Health System /ID# 155720	Detroit	Michigan
United States	Digestive Health Specialists of the Southeast /ID# 155719	Dothan	Alabama
United States	Gastro One /ID# 155729	Germantown	Tennessee
United States	Ruane Clinical Research Group /ID# 155714	Los Angeles	California
United States	TX Liver Inst, Americ Res Corp /ID# 157881	San Antonio	Texas
United States	Carolinas Center For Liver Dis /ID# 155731	Statesville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Germany,  Korea, Republic of,  New Zealand,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Wyles D, Weiland O, Yao B, Weilert F, Dufour JF, Gordon SC, Stoehr A, Brown A, Mauss S, Zhang Z, Pilot-Matias T, Rodrigues L Jr, Mensa FJ, Poordad F. Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection. J Hepatol. 2019 May;70(5):1019-1023. doi: 10.1016/j.jhep.2019.01.031. Epub 2019 Mar 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug.	12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen.
Secondary	Percentage of Participants With On-treatment Virologic Failure	On-treatment virologic failure was defined as meeting one of the following: confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) at any time point during the treatment period; or; confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA < 15 IU/mL during the treatment period, or; HCV RNA = 15 IU/mL at end of treatment with at least 6 weeks of treatment.	12 or 16 weeks depending on the treatment regimen
Secondary	Percentage of Participants With Post-treatment Relapse	Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment 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.	From the end of treatment (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen).