The Safety and Efficacy of Sequential Treatment of Ropeginterferon Alfa-2b (P1101) and Anti-PD1 in Interferon-Naive Adults With Chronic Hepatitis B or D Infection

NCT04638439 | Completed Phase 1 DMC

• 1 other identifier: A20-101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

Primary objective: To evaluate the safety and tolerability of sequential administration of P1101 and anti-PD1 in patient with chronic hepatitis B or D infection Secondary objectives:

1. 1.To explore HBsAg loss and kinetics during the study period
2. 2.To assess the anti-viral effect during the study period
3. 3.To evaluate the rate of ALT normalization

Conditions

Chronic Hepatitis B Infection; Chronic Hepatitis D Infection

Keywords

P1101; Anti-PD1; HBV; HDV

Outcome Measures

Primary Outcomes (2)

• Safety: AE/SAE

  Number of patients with adverse events, including SAEs

  Through study Follow-up Week 24 (up to 330 days)

• Safety: clinically significant abnormalities

  Number of patients with clinically significant abnormalities, including vital sign, physical examination, electrocardiogram (ECG) and laboratory data

  Through study Follow-up Week 24 (up to 330 days)

Secondary Outcomes (7)

• Subjects with HBsAg loss

  Treatment Week 12, Treatment Week 23, Follow-up Week 12 and Follow-up Week 24

• Subjects with HBsAg reduction from baseline

  Treatment Week 12, Treatment Week 23, Follow-up Week 12 and Follow-up Week 24

• Subjects with HBsAg seroconversion

  Treatment Week 12, Treatment Week 23, Follow-up Week 12 and Follow-up Week 24

• Subjects with undetectable HBV DNA

  Treatment Week 12, Treatment Week 23, Follow-up Week 12 and Follow-up Week 24

• Subjects with ≥ 2 log10 decline from baseline in HDV RNA

  Treatment Week 12, Treatment Week 23, Follow-up Week 12 and Follow-up Week 24

Study Arms (1)

P1101 + Nivolumab + Entecavir

EXPERIMENTAL

Drug: P1101 + Nivolumab + Entecavir

Interventions

P1101 + Nivolumab + Entecavir DRUG

P1101 (Ropeginterferon alfa-2b) 450 µg subcutaneously (SC) Q2W for 6 doses (12 weeks), followed by 0.3 mg/kg Nivolumab for 6 doses (12 weeks), with a follow up of 24 weeks. All patients will also receive Entecavir 0.5 mg QD from Day 1 to Follow-up 24.

Also known as: P1101 (Ropeginterferon alfa-2b) + Nivolumab + Entecavir

P1101 + Nivolumab + Entecavir

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Positive for HBsAg for at least 6 months, either HBeAg (+) or HBeAg (-), and ALT ≤ 10X ULN at screening;
• Interferon naïve;
• Quantitative HBsAg Level \< 5,000 IU/mL at screening; HBV DNA \< 2,000 IU/mL (patients are either under NUC treatment or not);
• Adults ≥20 years of age; patients who are over 70 years of age must be in generally good health depending upon the Investigator's judgment;
• Laboratory test results before study entry: WBC ≥ 3,000/mm3; ANC ≥ 1,500/mm3; Platelet ≥ 90,000/mm3; Hemoglobin ≥ 10g/dL; e-GFR ≥ 60mL/min;
• ECG without clinically significant abnormalities before study entry;
• Be able to attend all scheduled visits and to comply with all study procedures;
• Patients with anti-HDV (+) can be enrolled;
• Patients with fibrosis stage \< F3 can be enrolled;
• Willing to provide written informed consent;

You may not qualify if:

• Clinically significant illness or surgery that might interfere with study participation;
• Clinically significant vital sign abnormalities or fever \[body temperature \>38℃\]);
• History of significant alcohol or drug abuse within 6 months prior to the screening visit (alcohol consumption of more than 14 units of alcohol per week \[1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]) or refusal to abstain from alcohol or illicit drugs throughout the study;
• Any history or presence of poorly controlled or clinically significant medical conditions that are not suitable to receive interferon-based treatment, at the discretion of the investigator: major psychiatric (including but not limited to those with severe depression, severe bi-polar disorder, schizophrenia, suicidal ideation or history of suicidal attempt), neurological, cardiovascular (i.e. uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction), pulmonary, hematologic, immunologic, autoimmune diseases, thyroid or other endocrine diseases, metabolic (e.g. diabetes mellitus with HbA1C \> 8.0%) or other uncontrolled systemic disease, coagulation disorders or blood dyscrasias;
• Pregnant patient, female patient or the spouse of male patient, with child-bearing potential who is unwilling or unable to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicides, or birth control pills, or intrauterine devices throughout the study;
• History of severe allergic or hypersensitivity reactions, e.g. hypersensitivity to the active substance or to any of the excipients of Ropeginterferon alfa-2b (P1101), bronchospasm, angioedema, asthma, or anaphylaxis;
• Therapy with any systemic anti-viral treatment, anti-neoplastic, or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 1 month (3 months for those with long elimination half-lives) prior to the first dose of study drug;
• 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 or taking immunosuppressant;
• Use investigational drug of other clinical trials within 4 weeks prior to the first dose of the study drug;
• History of malignancy diagnosed or treated within 5 years prior to screening (except for localized treatment of squamous or non-invasive basal cell skin cancers; cervical carcinoma in situ);
• History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia);
• Serious localized infection (e.g., cellulitis, abscess) or systemic and life-threatening infection (e.g., septicemia) within 3 months prior to screening;
• Clinically significant medical conditions known to interfere absorption, distribution, metabolism or excretion of the study drugs;
• Decompensated liver disease, which includes but not limited to the following: total bilirubin≥2 mg/dL (except in Gilbert syndrome), direct bilirubin ≥2X ULN, albumin level \< 3.5 g/dL, INR ≥1.5; clinical evidence of ascites, liver decompensation, hepatic encephalopathy, oesophageal varices or cirrhosis as identified by ultrasound or any other examination before study entry;

Sponsors & Collaborators

• PharmaEssentia: lead

Study Sites (5)

Chia-Yi Christian Hospital

Chiayi City, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Nivolumab; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 20, 2020
• Study Start: August 17, 2022
• Primary Completion: May 14, 2025
• Study Completion: May 14, 2025
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (5)