Ropeginterferon Alfa-2b (P1101) Phase 3 Study in Interferon Treatment-Naive Subjects With HCV Genotype 2 Infection

Sponsor

PharmaEssentia (Industry)

Overall Status

Completed

CT.gov ID

NCT04382937

Collaborator

(none)

222

Enrollment

Locations

Arms

54.1

Actual Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary objective:

To demonstrate non-inferiority in sustained virologic response (SVR, undetectable HCV RNA at Follow up week 12) between PEG-Intron 1.5 µg per kg SC Q1W + Ribavirin 800-1400 mg PO daily and P1101 400 µg SC Q2W + Ribavirin 800-1400 mg PO daily for the treatment of chronic HCV genotype 2 infection

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus Infection	Drug: P1101 + Ribavirin Drug: PEG-Intron + Ribavirin	Phase 3

Detailed Description

Secondary objective:

To determine and compare the efficacy, safety, tolerability and immunogenicity of PEG-Intron 1.5 µg per kg SC Q1W + Ribavirin 800-1400 mg PO daily and P1101 400 µg SC Q2W + Ribavirin 800-1400 mg PO daily

Study Design

Study Type:

Interventional

Actual Enrollment :

222 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Randomized, Active Control Study to Demonstrate Non-Inferiority in Efficacy, and to Compare Safety and Tolerability of P1101 + Ribavirin to PEG-Intron + Ribavirin in Interferon Treatment-Naïve Subjects With Chronic HCV Genotype 2 Infection

Actual Study Start Date :

Jan 12, 2016

Actual Primary Completion Date :

Jul 15, 2020

Actual Study Completion Date :

Jul 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: P1101 + Ribavirin P1101 400 µg SC Q2W	Drug: P1101 + Ribavirin P1101 400 µg SC Q2W + Ribavirin 800-1400 mg PO daily Other Names: Ropeginterferon alfa-2b
Active Comparator: PEG-Intron + Ribavirin PEG-Intron 1.5 µg per kg SC Q1W	Drug: PEG-Intron + Ribavirin PEG-Intron 1.5 µg per kg SC Q1W + Ribavirin 800-1400 mg PO daily Other Names: Peginterferon alfa-2b

Arm

Intervention/Treatment

Experimental: P1101 + Ribavirin

P1101 400 µg SC Q2W

Drug: P1101 + Ribavirin

P1101 400 µg SC Q2W + Ribavirin 800-1400 mg PO daily

Other Names:

Ropeginterferon alfa-2b

Active Comparator: PEG-Intron + Ribavirin

PEG-Intron 1.5 µg per kg SC Q1W

Drug: PEG-Intron + Ribavirin

PEG-Intron 1.5 µg per kg SC Q1W + Ribavirin 800-1400 mg PO daily

Other Names:

Peginterferon alfa-2b

Outcome Measures

Primary Outcome Measures

Subjects with undetectable serum HCV RNA at follow up week 12 [Follow Week 12]
Percentage of subjects with SVR12 (undetectable serum HCV RNA, i.e. <12 IU/mL, at follow up week 12) in each treatment group

Secondary Outcome Measures

Subjects with undetectable serum HCV RNA [Treatment Week 4, 8, 12, 24 and Follow Week 24]
Percentage of subjects with undetectable serum HCV RNA at treatment week 4, 8, 12, 24 (end of treatment) and follow up week 24 in each treatment group
Number of subjects with adverse events [Through study Follow Week 24]
Number of subjects with adverse events in each treatment group
Number of subjects with clinically significant laboratory abnormalities [Through study Follow Week 24]
Number of subjects with clinically significant laboratory abnormalities in each treatment group
Subjects with anti-drug antibodies [Follow Week 12 and 24]
Percentage of subjects with positive anti-drug antibodies (the anti-peginterferon and the anti-Peg) at follow up week 12 and 24
Subjects with neutralizing antibody [Follow Week 12 and 24]
Percentage of subjects with positive neutralizing antibody at follow up week 12 and 24

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults ≥18 years of age (or other age required by local regulations); subjects who are over 70 years of age must be in generally good health.
Confirmed diagnosis of chronic hepatitis with HCV genotype 2 infection. Chronicity is defined as having proven clinical evidence of chronic hepatitis, e.g. a duration of disease longer than 24 weeks before dosing, OR positive for anti-HCV antibody and HCV RNA at screening with biopsy-proven chronic hepatitis C, OR fibrosis.
Compensated liver disease defined by normal or elevated ALT ≤10 x ULN, total bilirubin level <2 mg/dL (except in Gilbert's syndrome), normal albumin, normal INR (INR ≤1.5)
Interferon treatment naïve: never received any interferon.
No other known form of chronic liver disease apart from chronic hepatitis C infection. But mild and moderate fatty liver diseases can be included.
Hemoglobin ≥12 g/dL in men or ≥11 g/dL in women, WBC count ≥3,000/mm3, ANC ≥1,500/mm3, platelet count ≥90,000/mm3; and estimated glomerular filtration rate >60 mL/min.
Female and male subjects, and their partners of reproductive potential using effective means of contraception during the whole trial period.
Be able to attend all scheduled visits and to comply with all study procedures;
Be able to provide written informed consent.

Exclusion Criteria:

Any of the following is cause for exclusion from the study:

Decompensated liver disease, including overt clinical symptom and sign of complications related to portal hypertension.
Clinically significant illness or surgery within 4 weeks prior to dosing.
Any reason which, in the opinion of the investigator, would prevent the subject from participating in the study.
Positive test for hepatitis B surface antigen or human immunodeficiency virus at screening.
Clinically significant abnormal vital signs at screening.
Evidence of severe retinopathy by fundoscopy except age-related macular degeneration at screening.
Significant alcohol or illicit drug abuse within one year prior to the screening visit or refusal to abstain from excessive alcohol consumption as defined above or illicit drugs throughout the study.
Pregnant or breast feeding female subjects.
Therapy with any systemic anti-viral, anti-neoplastic, and immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 4 weeks prior to the first dose of study drug.
Use of an investigational drug or participation in an investigational drug trial within 4 weeks from the first dose.
Known clinically significant presence of any gastrointestinal pathology, clinically significant unresolved gastrointestinal symptoms, clinically significant liver (other than CHC) or clinically significant kidney disease (including but not limited to those with chronic renal failure on dialysis), or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug.
Hospital Anxiety and Depression Scale (HADS) score >10 on depression scale at screening that indicates clinically significant presence of depression determined by investigators.
Clinically significant presence of severe neurological disorders, e.g. uncontrolled seizure disorders.
Clinically significant presence of severe cardiovascular conditions and severe pulmonary conditions (including but not limited to pulmonary infiltrates, pneumonia, pneumonitis, chronic obstructive lung disease), uncontrolled immunologic, uncontrolled autoimmune, uncontrolled endocrine, uncontrolled metabolic, haematological, severe coagulation disorders or severe blood dyscrasias or other severe uncontrolled systemic disease.
A depot injection or an implant of any drug within 3 months prior to administration of study medication, other than contraception or hyaluronic acid injections in joints for osteoarthritis;
Body organ transplant and are taking immunosuppressants;
History of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured, and carcinoma in situ of cervix); However, subjects who are cancer survivors not on maintenance therapy and who had no malignant diseases history within the past 5 years could be recruited.
History of or ongoing opportunistic infection.
Serious local infection or systemic infection within the 3 months prior to screening.

Contacts and Locations

Locations

	Site	City	Country
1	Beijing Ditan Hospital Capital Medical University	Beijing	China
2	Gansu Wuwei Tumour Hospital	Gansu	China
3	The First Hospital of Lanzhou University	Gansu	China
4	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	China
5	Henan Provincial People's Hospital	Henan	China
6	Luoyang Central Hospital	Henan	China
7	The First Hospital of Jilin University	Jilin	China
8	Peace Hospital Affiliated to Changzhi Medical College	Shanxi	China
9	The Sixth People's Hospital of Shenyang	Shenyang	China
10	Tangdu Hospital, Fourth Military Medical University	Xi'an	China
11	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	China
12	Xijing Hospital, Fourth Military Medical University	Xi'an	China
13	Soonchunhyang University Seoul Hospital	Asan	Korea, Republic of
14	Pusan National University Hospital	Busan	Korea, Republic of
15	Kyungpook National University Hospital	Daegu	Korea, Republic of
16	Inha University Medical Center	Incheon	Korea, Republic of
17	Hanyang University Seoul Hospital	Seoul	Korea, Republic of
18	Seoul Metropolitan Government - Seoul National University Boramae Medical Center	Seoul	Korea, Republic of
19	Yonsei University Gangnam Severance Hospital	Seoul	Korea, Republic of
20	Saint Vincent Catholic Hospital	Suwon	Korea, Republic of
21	Changhua Christian Hospital	Changhua City	Taiwan
22	Chang Gung Memorial Hospital, Chiayi Branch	Chiayi City	Taiwan
23	Chia-Yi Christian Hospital	Chiayi City	Taiwan
24	Dalin Tzu Chi Hospital	Chiayi City	Taiwan
25	St. Martin De Porres Hospital	Chiayi City	Taiwan
26	Hualien Tzu Chi Hospital	Hualien City	Taiwan
27	Chang Gung Memorial Hospital, Kaohsiung Branch	Kaohsiung City	Taiwan
28	E-Da Hospital	Kaohsiung City	Taiwan
29	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City	Taiwan
30	Chang Gung Memorial Hospital, Keelung Branch	Keelung	Taiwan
31	Chang Gung Memorial Hospital, Linkou	New Taipei City	Taiwan
32	Taichung Veterans General Hospital	Taichung City	Taiwan
33	China Medical University Hospital	Taichung	Taiwan
34	Chi Mei Hospital, Liouying	Tainan City	Taiwan
35	Chi Mei Medical Center	Tainan City	Taiwan
36	National Cheng Kung University Hospital	Tainan City	Taiwan
37	National Taiwan University Hospital	Taipei City	Taiwan
38	Taitung MacKay Memorial Hospital	Taitung	Taiwan
39	National Taiwan University Hospital Yun-Lin Branch	Yuanlin	Taiwan