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A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection (CERTAIN-1)

Primary Purpose

Chronic Hepatitis C Virus, Hepatitis C Virus

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

ABT-493/ABT-530

OBV/PTV/r

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Virus focused on measuring Compensated cirrhosis, Non-cirrhotic, Renal impairment, Hepatitis C virus (HCV), Hepatitis C, Chronic Hepatitis C, Hepatitis C Genotype 1, Hepatitis C Genotype 2, Hepatitis C Genotype 3, Hepatitis C Genotype 4, Hepatitis C Genotype 5, Hepatitis C Genotype 6, DAA-experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Females were postmenopausal for at least 2 years; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug.
Screening central laboratory result indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype.
Chronic HCV infection is defined as one of the following:
- Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening.
- A liver biopsy consistent with chronic HCV infection.
Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures.
Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements.
Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI).

Exclusion Criteria:

Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was pregnant or planning to become pregnant during the study.
Participants co-infected with hepatitis B virus or human immunodeficiency virus.
Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug.
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.
Any cause of liver disease other than chronic HCV infection.
Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease.
Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm D

Arm Description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) once daily (QD) for 8 weeks in HCV genotype(GT)1 -infected, DAA treatment-naïve participants without cirrhosis.

Ombitasvir (25 mg)/paritaprevir (150 mg)/ritonavir (100mg) (OBV/PTV/r) QD for 12 weeks in HCV GT1 infected, DAA treatment-naïve participants without cirrhosis.

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120mg) QD for 12 weeks in HCV GT1- or GT2-infected participants with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected participants (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected participants who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), and HCV GT1- or GT2-infected participants with severe renal impairment and compensated cirrhosis.

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in GT1- or GT2-infected participants with severe renal impairment and without cirrhosis.

Outcomes

Primary Outcome Measures

Percentage of Participants in Arms A and B 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]) 12 weeks after the last dose of study drug.

Secondary Outcome Measures

Percentage of Participants in Arm A 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]) 12 weeks after the last dose of study drug. 95% CI was calculated using the normal approximation to the binomial distribution.

Percentage of Participants for Each Sub-Population in Arms C and D 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]) 12 weeks after the last dose of study drug. Subpopulations defined as Genotype 1 and 2 infected cirrhotic participants, prior direct acting antiviral agent (DAA) treatment experienced (T-exp) participants, Genotype 3, 4, 5 or 6-infected participants, and participants with severe renal impairment (RI). 95% CI was calculated using the Wilson score method.

Percentage of Participants With On-treatment Virologic Failure

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. 95% CI was calculated using the Wilson score method.

Percentage of Participants With Post-Treatment Relapse

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 with HCV RNA levels < LLOQ at the end of treatment, excluding participants who were been shown to be re-infected. The confidence interval was calculated using the Wilson score method.

Full Information

NCT ID

NCT02707952

First Posted

March 9, 2016

Last Updated

July 14, 2021

Sponsor

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02707952

Brief Title

A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection

Acronym

CERTAIN-1

Official Title

A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection (CERTAIN-1)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

February 22, 2016 (Actual)

Primary Completion Date

November 14, 2016 (Actual)

Study Completion Date

February 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this phase 3, multicenter study is to evaluate the efficacy and safety of ABT-493/ABT-530 in Japanese adults with chronic Hepatitis C Virus (HCV)-infected, HCV direct-acting antiviral agent (DAA) treatment-naïve, and DAA treatment-experienced Japanese adult subjects.

Detailed Description

The study consisted of two sub-studies that enrolled in parallel. Substudy 1 was randomized, open-label, and active-controlled, wherein HCV treatment-naïve or interferon (IFN)-experienced (i.e., DAA treatment-naïve), genotype (GT)1-infected participants without cirrhosis were enrolled. Substudy 2 was non-randomized, open label, and enrolled special populations of HCV-infected participants [GT1- or GT2-infected subjects with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected subjects (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected subjects who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), HCV GT1- or GT2-infected subjects with severe renal impairment (with compensated cirrhosis or without cirrhosis)].

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C Virus, Hepatitis C Virus

Keywords

Compensated cirrhosis, Non-cirrhotic, Renal impairment, Hepatitis C virus (HCV), Hepatitis C, Chronic Hepatitis C, Hepatitis C Genotype 1, Hepatitis C Genotype 2, Hepatitis C Genotype 3, Hepatitis C Genotype 4, Hepatitis C Genotype 5, Hepatitis C Genotype 6, DAA-experienced

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

295 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) once daily (QD) for 8 weeks in HCV genotype(GT)1 -infected, DAA treatment-naïve participants without cirrhosis.

Arm Title

Arm B

Arm Type

Active Comparator

Arm Description

Ombitasvir (25 mg)/paritaprevir (150 mg)/ritonavir (100mg) (OBV/PTV/r) QD for 12 weeks in HCV GT1 infected, DAA treatment-naïve participants without cirrhosis.

Arm Title

Arm C

Arm Type

Experimental

Arm Description

Arm Title

Arm D

Arm Type

Experimental

Arm Description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in GT1- or GT2-infected participants with severe renal impairment and without cirrhosis.

Intervention Type

Drug

Intervention Name(s)

ABT-493/ABT-530

Other Intervention Name(s)

Glecaprevir/Pibrentasvir, glecaprevir (ABT-493), pibrentasvir (ABT-530)

Intervention Description

Co-formulated tablet

Intervention Type

Drug

Intervention Name(s)

OBV/PTV/r

Other Intervention Name(s)

Ombitasvir/paritaprevir/ritonavir, ombitasvir (ABT-267), paritaprevir (ABT-450), norvir (ritonavir)

Intervention Description

Co-formulated tablet

Primary Outcome Measure Information:

Title

Percentage of Participants in Arms A and B 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

Secondary Outcome Measure Information:

Title

Percentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Description

Time Frame

12 weeks after the last actual dose of study drug

Title

Percentage of Participants for Each Sub-Population in Arms C and D With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Description

Time Frame

12 weeks after the last actual dose of study drug

Title

Percentage of Participants With On-treatment Virologic Failure

Description

Time Frame

Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment

Title

Percentage of Participants With Post-Treatment Relapse

Description

Time Frame

From the end of treatment through 12 weeks after the last dose of study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Females were postmenopausal for at least 2 years; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug. Screening central laboratory result indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype. Chronic HCV infection is defined as one of the following: Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening. A liver biopsy consistent with chronic HCV infection. Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures. Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements. Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). Exclusion Criteria: Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was pregnant or planning to become pregnant during the study. Participants co-infected with hepatitis B virus or human immunodeficiency virus. Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug. 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. Any cause of liver disease other than chronic HCV infection. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease. Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

AbbVie Inc.

Organizational Affiliation

AbbVie

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

28948366

Citation

Chayama K, Suzuki F, Karino Y, Kawakami Y, Sato K, Atarashi T, Naganuma A, Watanabe T, Eguchi Y, Yoshiji H, Seike M, Takei Y, Kato K, Alves K, Burroughs M, Redman R, Pugatch DL, Pilot-Matias TJ, Krishnan P, Oberoi RK, Xie W, Kumada H. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis. J Gastroenterol. 2018 Apr;53(4):557-565. doi: 10.1007/s00535-017-1391-5. Epub 2017 Sep 25.

Results Reference

background

PubMed Identifier

35174470

Citation

Brown RS Jr, Collins MA, Strasser SI, Emmett A, Topp AS, Burroughs M, Ferreira R, Feld JJ. Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension. Infect Dis Ther. 2022 Apr;11(2):913-924. doi: 10.1007/s40121-022-00599-8. Epub 2022 Feb 17.

Results Reference

derived

PubMed Identifier

30868245

Citation

Naganuma A, Chayama K, Notsumata K, Gane E, Foster GR, Wyles D, Kwo P, Crown E, Bhagat A, Mensa FJ, Otani T, Larsen L, Burroughs M, Kumada H. Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection. J Gastroenterol. 2019 Aug;54(8):752-761. doi: 10.1007/s00535-019-01569-7. Epub 2019 Mar 13.

Results Reference

derived

PubMed Identifier

29180522

Citation

Krishnan P, Schnell G, Tripathi R, Beyer J, Reisch T, Dekhtyar T, Irvin M, Xie W, Fu B, Burroughs M, Redman R, Kumada H, Chayama K, Collins C, Pilot-Matias T. Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan. Antimicrob Agents Chemother. 2018 Jan 25;62(2):e02217-17. doi: 10.1128/AAC.02217-17. Print 2018 Feb.

Results Reference

derived

PubMed Identifier

28941361

Citation

Yartel AK, Rein DB, Brown KA, Krauskopf K, Massoud OI, Jordan C, Kil N, Federman AD, Nerenz DR, Brady JE, Kruger DL, Smith BD. Hepatitis C virus testing for case identification in persons born during 1945-1965: Results from three randomized controlled trials. Hepatology. 2018 Feb;67(2):524-533. doi: 10.1002/hep.29548. Epub 2018 Jan 2.

Results Reference

derived

PubMed Identifier

28865152

Citation

Toyoda H, Chayama K, Suzuki F, Sato K, Atarashi T, Watanabe T, Atsukawa M, Naganuma A, Notsumata K, Osaki Y, Nakamuta M, Takaguchi K, Saito S, Kato K, Pugatch D, Burroughs M, Redman R, Alves K, Pilot-Matias TJ, Oberoi RK, Fu B, Kumada H. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection. Hepatology. 2018 Feb;67(2):505-513. doi: 10.1002/hep.29510. Epub 2017 Nov 24.

Results Reference

derived

Links:

URL

http://www.rxabbvie.com/

Description

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A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection

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