Safety, Tolerability, Pharmacokinetics & Pharmacodynamics Study of Ropeginterferon Alfa-2b in Healthy Japanese and Caucasian Subjects

NCT03546465 | Completed Phase 1 FDA Drug

• 1 other identifier: A17-102
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 single center, parallel group study to assess and compare the safety, tolerability, PK and PD of 4 single ascending doses of P1101 (100, 200, 300, and 450 μg) following subcutaneous administration in healthy Japanese and Caucasian subjects.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (12)

• Adverse events after single dose

  Frequency and severity of all adverse events among subjects, including frequency and severity of drug-related adverse events.

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration \[AUC(0-last)\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Area under the plasma concentration-time curve from time zero extrapolated to infinity \[AUC(0-inf)\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Observed maximum plasma concentration \[Cmax\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Time to reach Cmax \[tmax\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  apparent terminal rate constant

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Apparent terminal half-life \[t½\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Apparent systemic clearance \[CL/F\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  apparent volume of distribution during the terminal phase \[Vz/F\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  dose normalized AUC(0-last) \[AUC(0-last)/Dose\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  dose normalized AUC(0-inf) \[AUC(0-inf)/Dose\]

  Through study Day 35

• Pharmacokinetics of ropeginterferon alfa-2b after single dose

  Dose normalized Cmax \[Cmax/Dose\]

  Through study Day 35

Secondary Outcomes (6)

• Pharmacodynamics of ropeginterferon alfa-2b after single dose

  Through study Day 35

• Pharmacodynamics of ropeginterferon alfa-2b after single dose

  Through study Day 35

• Pharmacodynamics of ropeginterferon alfa-2b after single dose

  Through study Day 35

• Pharmacodynamics of ropeginterferon alfa-2b after single dose

  Through study Day 35

• Pharmacodynamics of ropeginterferon alfa-2b after single dose

  Through study Day 35

Study Arms (8)

Cohorts 1C (Caucasian subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 100 μg

Drug: ropeginterferon alfa-2b

Cohorts 1J (Japanese subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 100 μg

Drug: ropeginterferon alfa-2b

Cohorts 2C (Caucasian subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 200 μg

Drug: ropeginterferon alfa-2b

Cohorts 2J (Japanese subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 200 μg

Drug: ropeginterferon alfa-2b

Cohorts 3C (Caucasian subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 300 μg

Drug: ropeginterferon alfa-2b

Cohorts 3J (Japanese subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 300 μg

Drug: ropeginterferon alfa-2b

Cohorts 4C (Caucasian subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 450 μg

Drug: ropeginterferon alfa-2b

Cohorts 4J (Japanese subjects)

EXPERIMENTAL

ropeginterferon alfa-2b: single dose of 450 μg

Drug: ropeginterferon alfa-2b

Interventions

ropeginterferon alfa-2b DRUG

6 subjects in each cohort will receive a single dose by subcutaneous injection

Also known as: P1101

Cohorts 1C (Caucasian subjects); Cohorts 1J (Japanese subjects); Cohorts 2C (Caucasian subjects); Cohorts 2J (Japanese subjects); Cohorts 3C (Caucasian subjects); Cohorts 3J (Japanese subjects); Cohorts 4C (Caucasian subjects); Cohorts 4J (Japanese subjects)

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects are eligible to be included in the study only if all of the following criteria apply:
• Adult Japanese and Caucasian males aged 21 to 50 years inclusive and body mass index (BMI) between 19 and 30 kg/m2.
• Japanese subjects must be first generation (born in Japan) with parents and grandparents born in Japan, lived for \< 10 years outside of Japan, and have no significant change in life style since leaving Japan.
• Caucasian subjects must have both parents of Caucasian descent; Caucasian subjects are defined as descendants of the original peoples of Europe.
• Individual Caucasian subjects should be selected to match body weight (± 20%) and height (± 15%) of corresponding Japanese subjects.
• Subjects must be willing to use effective methods of contraception during the entire study period and for 12 weeks after dosing on Day 1.
• Subjects who are healthy as determined by pre-study medical history, physical examination, and 12-lead ECG.
• Subjects whose clinical laboratory test results are within the reference ranges for hematological parameters and liver function tests at Screening and Day -1. For results outside the reference range at Screening and considered not clinically significant by the Investigator a repeat test is allowed once during the Screening period. Note: subjects with an absolute neutrophil count below 2.0 × 109/L will be excluded. All other clinical laboratory test results must be within the reference range or judged not to be clinically significant and acceptable to the Investigator.
• Subjects whose thyroid function tests are within the study reference range.
• Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb) and human immunodeficiency virus (HIV) I and II tests at Screening.
• Subjects who are negative for drugs of abuse and alcohol tests at Screening. Alcohol will be measured using breathalyzer test. If the tests are negative at Screening, and if they meet other eligibility criteria, the subject may be included. A repeat test for suspected false positive at Screening (with documented rationale) may be performed at the discretion of the Investigator. However, if the tests are subsequently positive on Admission, the subject should be withdrawn from the study. Repeat tests are not allowed at Admission.
• Subjects who are non-smokers for at least 6 months preceding Screening.
• Subjects who are able and willing to give a valid written informed consent.

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply:
• Female subjects.
• Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, coagulation, endocrine, lymphatic, neurological, cardiovascular, psychiatric, ophthalmological, musculoskeletal, genitourinary, immunological, autoimmune, dermatological, and connective tissue diseases or disorders.
• Subjects who have a first degree relative with autoimmune disease (e.g. thyroiditis, lupus, rheumatoid arthritis, etc.) or other clinically relevant medical history which in the opinion of the Investigator poses a risk to the subject.
• Subjects with a history of latent or active tuberculosis or exposure to endemic areas.
• Subjects with a positive result in the QuantiFERON-TB Gold test and/or clinically significant abnormality on chest X-ray.
• Subjects who have a clinically relevant surgical history and history of any prior malignancy.
• Subjects who, in the opinion of the Investigator, have clinically relevant medical history in their immediate family (first degree relative).
• Subjects with current symptoms of eczema or hay fever, or subjects with a history of hay fever requiring medication when their hay fever season starts within the expected duration of the study.
• Subjects who have a history of severe allergy and severe drug reaction (e.g., anaphylaxis, or other drug reaction requiring hospitalization to beta lactam antibiotics OR any other relevant drug hypersensitivity).
• Subjects who have a history of alcoholism.
• Subjects who consume more than the recommended number of 14 units of alcohol per week. (1 unit = 1 glass of wine \[125 mL\] = 1 measure of spirits = ½ pint of beer).
• Subjects who have a history of drug abuse.
• Subjects who have abnormal vital signs, after 10 minutes supine rest (measurements may be repeated after 15 minutes at the discretion of the Investigator where they suspect that the initial values are not representative of the usual values due to some factors e.g., anxiety), defined as any of the following at Screening:
• Systolic blood pressure \< 90 mmHg or ≥ 140 mmHg;

Sponsors & Collaborators

• PharmaEssentia Japan K.K.: lead
• PharmaEssentia: collaborator

Study Sites (1)

Nucleus Network Limited

Melbourne, Victoria, 3004, Australia

Location

Related Publications (2)

• Qin A, Shimoda K, Suo S, Fu R, Kirito K, Wu D, Liao J, Chen H, Wu L, Su X, Gao Y, Sato T, Li Y, Zhang J, Shen W, Wang W, Zhang L, Jin J, Komatsu N. Population Pharmacokinetics-Pharmacodynamics and Exposure-Response of Ropeginterferon Alfa-2b in Chinese and Japanese Patients With Polycythemia Vera. Pharmacol Res Perspect. 2025 Jun;13(3):e70109. doi: 10.1002/prp2.70109.

  PMID: 40313042 DERIVED

• Miyachi N, Zagrijtschuk O, Kang L, Yonezu K, Qin A. Pharmacokinetics and Pharmacodynamics of Ropeginterferon Alfa-2b in Healthy Japanese and Caucasian Subjects After Single Subcutaneous Administration. Clin Drug Investig. 2021 Apr;41(4):391-404. doi: 10.1007/s40261-021-01026-5. Epub 2021 Mar 16.

  PMID: 33725322 DERIVED

Study Officials

• Jason Lickliter, MD

  Nucleus Network Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2018
• First Posted: June 6, 2018
• Study Start: May 7, 2018
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: November 26, 2019

Record last verified: 2019-11

Locations

AU (1)