Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Ropeginterferon Alfa-2b in Healthy Chinese Subjects

Huang, Yi‐Wen; Tsai, Chan Yen; Tsai, Chung Wei; Wang, William Yang; Zhang, Jingjing; Qin, Albert; Teng, Ching‐Leou; Song, Bo; Wang, Mei Xia

doi:10.1007/s12325-021-01863-y

Cited by 18 publications

(26 citation statements)

References 22 publications

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“…Similar results were also observed in a similar phase I trial of Japanese and Caucasian healthy subjects who received a single subcutaneous injection of ropeginterferon alfa‐2b at the doses of 100, 200 or 300 μg 37 where a dose‐dependent induction of beta‐2 microglobulin (β2M)/neopterin was seen. Furthermore, another similar phase I study conducted in healthy Chinese adult subjects who received a single subcutaneous injection of pegylated IFN alfa‐2a at the dose of 180 μg or ropeginterferon alfa‐2b at the doses of 90, 180 or 270 μg reported a similar dose‐dependent increase of the drug exposure ( C max , AUC 0‐ t , AUC 0‐∞ ) 38 …”

Section: Discussionmentioning

confidence: 71%

“…In this first‐in‐human study, ropeginterferon alfa‐2b showed a similar safety profile to pegylated IFN alfa‐2b. To further evaluate the safety and PK/PD profiles of ropeginterferon alfa‐2b among different ethnic and racial groups, we also conducted studies in Japanese/Caucasian and Chinese populations 37,38 . These studies indicated that ropeginterferon alfa‐2b up to 270 μg was safe and well tolerated.…”

Section: Discussionmentioning

confidence: 99%

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Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

Huang

Qin²,

Fang

et al. 2021

Brit J Clinical Pharma

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We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).Methods: Thirty-six subjects received single subcutaneous injection of ropeginterferon alfa-2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa-2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa-2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa-2a.Results: Adverse events in ropeginterferon alfa-2b and pegylated IFN alfa-2a groups were similar, and most of them were mild or moderate. Mean C max increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa-2b groups and was 12.95 ng/mL for pegylated IFN alfa-2a. At 180 μg, ropeginterferon alfa-2b showed statistically significant C max geometric mean ratio (1.76; P = .0275).Mean T max ranged from 74.52 to 115.69 h for ropeginterferon alfa-2b groups, and was 84.25 h for pegylated IFN alfa-2a. Mean AUC 0-t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa-2b groups, while for pegylated IFN alfa-2a it was found to be 2706 ng•h/mL in pegylated IFN alfa-2a.For neopterin and 2 0 ,5 0 -oligoadenylate synthase, mean E max , T max and AUC 0-t of ropeginterferon alfa-2b were similar to those of pegylated IFNα-2a at 180 μg. Conclusion:Ropeginterferon alfa-2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa-2b showed increase in dose-response. Ropeginterferon alfa-2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa-2a at the same dose level.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

Huang

Qin²,

Fang

et al. 2021

Brit J Clinical Pharma

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“…It exists as one major form as opposed to the 8–14 isomers of other pegylated IFN alfa products. It has improved pharmacokinetic parameters and exhibited favorable safety profiles [ 15 – 17 , 24 ]. It was approved in 2019 for the treatment of polycythemia vera by the European commission in Europe and is now approved or under consideration for approval in the treatment of polycythemia vera in more countries.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, the safety of ropeginterferon alfa-2b has been well studied in multiple studies in patients with polycythemia vera , chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, and healthy subjects. Ropeginterferon alfa-2b was found to be generally well tolerated in these studies [ 15 – 17 , 19 , 20 ]. In this study, adverse events (AEs) were also examined.…”

Section: Methodsmentioning

confidence: 99%

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Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan

Chen

Lee

Qin³

et al. 2021

Adv Ther

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Introduction This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. Methods We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. Results Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). Conclusions Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01998-y.

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A Phase 3 clinical trial validating the potency and safety of an innovative, extra‐long‐acting interferon in chronic hepatitis C

Chen

Chuang

Qin³

et al. 2022

JGH Open

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Background and Aim Ropeginterferon alfa‐2b is a novel mono‐pegylated, extra‐long‐acting interferon. It is administered infrequently and showed good tolerability and clinical activity for the chronic hepatitis B or C treatment in our previous Phase 2 clinical trials. This study aims to validate the potency and safety of this novel agent in a Phase 3 chronic viral hepatitis setting. Methods Patients with chronic hepatitis C genotype 2 were randomized to receive subcutaneous injections of ropeginterferon alfa‐2b biweekly or the conventional pegylated interferon alfa‐2b weekly for 24 weeks, combined with ribavirin. The primary endpoint was to assess the safety and antiviral potency of ropeginterferon alfa‐2b by the non‐inferiority in sustained virologic response at 12 weeks after treatment. Results A total of 222 patients were enrolled. Ropeginterferon alfa‐2b group showed a favorable safety profile. Side effects that were generally associated with prior interferon therapies, including neutropenia, asthenia, fatigue, alopecia, dizziness, decreased appetite, nausea, flu‐like symptoms including myalgia, pyrexia, and headache, and administration site reactions, were notably less in the ropeginterferon alfa‐2b group. The cumulative incidence of adverse events of special interest was also notably higher in the control group. The primary endpoint was met and ropeginterferon alfa‐2b showed a better SVR12 rate of 79.8% than 71.9% of the control group. Conclusion Ropeginterferon alfa‐2b is efficacious and has a favorable safety profile as compared with the conventional pegylated interferon alfa‐2b. This study together with previous Phase 2 data validated ropeginterferon alfa‐2b to be a new treatment option for chronic hepatitis C genotype 2.

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Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Ropeginterferon Alfa-2b in Healthy Chinese Subjects

Cited by 18 publications

References 22 publications

Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan

A Phase 3 clinical trial validating the potency and safety of an innovative, extra‐long‐acting interferon in chronic hepatitis C

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