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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03546465




Registration number
NCT03546465
Ethics application status
Date submitted
6/05/2018
Date registered
22/05/2018
Date last updated
22/05/2018

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics & Pharmacodynamics Study of Ropeginterferon Alfa-2b in Healthy Japanese and Caucasian Subjects
Scientific title
A Phase 1 Bridging Study to Investigate and Compare the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Four Single Ascending Doses of Ropeginterferon Alfa-2b (P1101) in Healthy Japanese and Healthy Caucasian Subjects
Secondary ID [1] 0 0
A17-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ropeginterferon alfa-2b

Experimental: Cohorts 1C (Caucasian subjects) - ropeginterferon alfa-2b: single dose of 100 µg

Experimental: Cohorts 1J (Japanese subjects) - ropeginterferon alfa-2b: single dose of 100 µg

Experimental: Cohorts 2C (Caucasian subjects) - ropeginterferon alfa-2b: single dose of 200 µg

Experimental: Cohorts 2J (Japanese subjects) - ropeginterferon alfa-2b: single dose of 200 µg

Experimental: Cohorts 3C (Caucasian subjects) - ropeginterferon alfa-2b: single dose of 300 µg

Experimental: Cohorts 3J (Japanese subjects) - ropeginterferon alfa-2b: single dose of 300 µg

Experimental: Cohorts 4C (Caucasian subjects) - ropeginterferon alfa-2b: single dose of 450 µg

Experimental: Cohorts 4J (Japanese subjects) - ropeginterferon alfa-2b: single dose of 450 µg


Treatment: Drugs: ropeginterferon alfa-2b
6 subjects in each cohort will receive a single dose by subcutaneous injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events after single dose - Frequency and severity of all adverse events among subjects, including frequency and severity of drug-related adverse events.
Timepoint [1] 0 0
Through study Day 35
Primary outcome [2] 0 0
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)]
Timepoint [2] 0 0
Through study Day 35
Primary outcome [3] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Area under the plasma concentration-time curve from time zero extrapolated to infinity [AUC(0-inf)]
Timepoint [3] 0 0
Through study Day 35
Primary outcome [4] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Observed maximum plasma concentration [Cmax]
Timepoint [4] 0 0
Through study Day 35
Primary outcome [5] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Time to reach Cmax [tmax]
Timepoint [5] 0 0
Through study Day 35
Primary outcome [6] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - apparent terminal rate constant
Timepoint [6] 0 0
Through study Day 35
Primary outcome [7] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Apparent terminal half-life [t½]
Timepoint [7] 0 0
Through study Day 35
Primary outcome [8] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Apparent systemic clearance [CL/F]
Timepoint [8] 0 0
Through study Day 35
Primary outcome [9] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - apparent volume of distribution during the terminal phase [Vz/F]
Timepoint [9] 0 0
Through study Day 35
Primary outcome [10] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - dose normalized AUC(0-last) [AUC(0-last)/Dose]
Timepoint [10] 0 0
Through study Day 35
Primary outcome [11] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - dose normalized AUC(0-inf) [AUC(0-inf)/Dose]
Timepoint [11] 0 0
Through study Day 35
Primary outcome [12] 0 0
Pharmacokinetics of ropeginterferon alfa-2b after single dose - Dose normalized Cmax [Cmax/Dose]
Timepoint [12] 0 0
Through study Day 35
Secondary outcome [1] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Beta-2 microglobulin: maximum serum biomarker response [Emax]
Timepoint [1] 0 0
Through study Day 35
Secondary outcome [2] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Beta-2 microglobulin: time to Emax [TEmax]
Timepoint [2] 0 0
Through study Day 35
Secondary outcome [3] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Beta-2 microglobulin: area under the serum biomarker effect-time curve [AUEC(0-t)]
Timepoint [3] 0 0
Through study Day 35
Secondary outcome [4] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Neopterin: maximum serum biomarker response [Emax]
Timepoint [4] 0 0
Through study Day 35
Secondary outcome [5] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Neopterin: time to Emax [TEmax]
Timepoint [5] 0 0
Through study Day 35
Secondary outcome [6] 0 0
Pharmacodynamics of ropeginterferon alfa-2b after single dose - Neopterin: area under the serum biomarker effect-time curve [AUEC(0-t)]
Timepoint [6] 0 0
Through study Day 35

Eligibility
Key inclusion criteria
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.
Minimum age
21 Years
Maximum age
50 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects are excluded from the study if any of the following criteria apply:

- Subjects who do not conform to the above inclusion criteria.

- 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:

1. Systolic blood pressure < 90 mmHg or = 140 mmHg;

2. Diastolic blood pressure < 50 mmHg or = 90 mmHg;

3. Pulse rate < 40 or > 100 beats per minute.

- Subjects who have any clinically important abnormalities in rhythm, conduction or
morphology of the resting ECG and any clinically important abnormalities in the
12-lead ECG as considered by the Investigator that may interfere with the
interpretation of QTc interval changes.

- Subjects who have a prolonged QTcF > 450 ms or family history of long QT syndrome.

- Subjects who have a significant infection such as a respiratory infection or known
inflammatory process at Screening or Admission.

- Subjects who have a clinically significant history or evidence of any active or
suspected bacterial, viral, fungal or parasitic infection within the 30 days prior to
Admission (e.g., common cold, viral syndrome, flu-like symptoms, etc).

- Subjects who have acute gastrointestinal symptoms at Screening or Admission (e.g.,
nausea, vomiting, diarrhea, and heartburn).

- Subjects who have used 1 or more prescription drugs within 28 days prior to Day 1.

- Subjects who have used non-prescription drugs or other products (supplements, herbal
preparations, etc) with enzyme inducing properties such as St John's Wort within 28
days prior to the first administration of investigational product.

- Subjects who have used other non-prescription drugs excluding routine vitamins but
including megadose (intake of 20 to 600 times the recommended daily dose) vitamin
therapy within 7 days of first administration of investigational product, unless
agreed as not clinically relevant by the Principal Investigator and Sponsor.

- Subjects who have received any live vaccine in the 6 months prior to Screening.

- Subjects who have previously been exposed to interferon or peginterferon.

- Subjects who have received the last dose of investigational product within the last 3
months or within 5 times the half-life, whichever is longer and those who are on
extended follow-up.

- Subjects who are vegans or have medical dietary restrictions.

- Subjects who have consumed grapefruit, grapefruit juice, Seville oranges, Seville
orange marmalade, or other products containing grapefruit or Seville oranges within 7
days of the first administration of investigational product.

- Subjects who have donated blood/plasma within 3 months of Screening or who have had
any blood loss > 500 mL during the 3 months prior to Screening.

- Subjects who are staff members at the investigational site.

- Subjects who are Contract Research Organization staff members, Sponsor employees, and
affiliates.

- Subjects who cannot understand or communicate reliably with the Investigator.

- Subjects who are unlikely to co-operate with the requirements of the study.

- Subjects who have been shown to have a suicidal tendency following completion of the
C-SSRS.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network Limited - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
PharmaEssentia Japan K.K.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PharmaEssentia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03546465
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason Lickliter, MD
Address 0 0
Nucleus Network Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Narihisa Miyachi
Address 0 0
Country 0 0
Phone 0 0
+81-3-6866-9531
Fax 0 0
Email 0 0
narihisa_miyachi@pharmaessentia.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable