Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis.

Abstract

BACKGROUND:

The once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan.

METHODS:

CERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks. The primary efficacy endpoint was non-inferiority of G/P compared to OBV/PTV/r by assessing SVR at post-treatment week 12 (SVR12) among non-cirrhotic patients without the NS5A Y93H polymorphism.

RESULTS:

SVR12 was achieved by 128/129 (99.2%; one patient lost to follow-up) non-cirrhotic patients in the 8-week G/P Arm (including 23/23 patients with the NS5A Y93H polymorphism) and 52/52 (100%) patients in the 12-week OBV/PTV/r Arm. No patients from the G/P Arm prematurely discontinued the study drug or experienced a treatment-emergent serious adverse event (TESAE). Three patients from the OBV/PTV/r Arm experienced five TESAEs and one of these patients discontinued the study drug due to TESAEs. All 38 (100%) patients with compensated cirrhosis achieved SVR12; in this group, no TESAEs were reported and one patient discontinued treatment due to an AE.

CONCLUSIONS:

CERTAIN-1 study results demonstrate high efficacy and favorable tolerability of G/P in GT1-infected Japanese patients including those with the NS5A Y93H polymorphism, with no virologic failures observed.

• Authors: Kazuaki Chayama, Fumitaka Suzuki, Yoshiyasu Karino, Yoshiiku Kawakami, Ken Sato, Tomofumi Atarashi, Atsushi Naganuma, Tsunamasa Watanabe, Yuichiro Eguchi, Hitoshi Yoshiji, Masataka Seike, Yoshiyuki Takei, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David L Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 53 Issue 4 Pg. 557-565 (Apr 2018) ISSN: 1435-5922 [Electronic] Japan
• PMID: 28948366 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Aminoisobutyric Acids
• Anilides
• Antiviral Agents
• Benzimidazoles
• Carbamates
• Cyclopropanes
• Drug Combinations
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Pyrrolidines
• Quinoxalines
• RNA, Viral
• Sulfonamides
• Viral Nonstructural Proteins
• ombitasvir
• pibrentasvir
• Proline
• NS-5 protein, hepatitis C virus
• Leucine
• Valine
• glecaprevir
• Ritonavir
• paritaprevir

Topics

• Adult
• Age Distribution
• Aged
• Aged, 80 and over
• Aminoisobutyric Acids
• Anilides (therapeutic use)
• Antiviral Agents (adverse effects, blood, therapeutic use)
• Benzimidazoles (adverse effects, blood, therapeutic use)
• Carbamates (therapeutic use)
• Cyclopropanes
• Drug Administration Schedule
• Drug Combinations
• Drug Therapy, Combination
• Female
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (blood, complications, drug therapy, virology)
• Humans
• Lactams, Macrocyclic
• Leucine (analogs & derivatives)
• Liver Cirrhosis (blood, drug therapy, virology)
• Macrocyclic Compounds (therapeutic use)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Pyrrolidines
• Quinoxalines (adverse effects, blood, therapeutic use)
• RNA, Viral (blood)
• Ritonavir (therapeutic use)
• Sulfonamides (adverse effects, blood, therapeutic use)
• Sustained Virologic Response
• Valine
• Viral Nonstructural Proteins (genetics)