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Trial registered on ANZCTR


Registration number
ACTRN12615000218594
Ethics application status
Approved
Date submitted
23/02/2015
Date registered
5/03/2015
Date last updated
26/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison study of PF530 and Betaferon in healthy subjects
Scientific title
A Phase 1 Double-Blind, Randomised, Two-Treatment Cross-over Study Comparing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PF530 and Betaferon Administered by Subcutaneous Injection in Healthy Adult Volunteers
Secondary ID [1] 286227 0
PF530-101
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 294272 0
Condition category
Condition code
Neurological 294594 294594 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this study, half the participants will be receive PF530 and the other half, Betaferon comparator in Period 1. After a 14 day washout period, participants will swap over so that those who received PF530 will be receive Betaferon comparator and vice versa in Period 2.
PF530/Betaferon comparator is given as a single dose of 0.25mg given as a subcutaneous injection in both study periods.
The study will consist of two parts (Part I and Part II). Twelve participants will be enrolled in Part I, and the results of this part will determine how many participants will be enrolled in Part II.
Intervention code [1] 291245 0
Treatment: Drugs
Comparator / control treatment
Betaferon
Control group
Active

Outcomes
Primary outcome [1] 294365 0
To test the safety and tolerability of PF530 and Betaferon
Safety and tolerability will be assessed through recording and collection of adverse events, looking at any local injection site reactions (e.g. redness, pain, tenderness), changes in laboratory results, measuring vital signs (blood pressure, heart rate) and changes in electrocardiogram (ECG).

Timepoint [1] 294365 0
Safety and tolerability will be assessed from randomisation (Day 1) through to Day 28.
Secondary outcome [1] 313108 0
To assess the pharmacokinetics of PF530 compared to Betaferon
Pharmacokinetics will be assessed through collection of blood samples at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24 and 36 hours post dose
Timepoint [1] 313108 0
Pharmacokinetics blood samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24 and 36 hours post dose
Secondary outcome [2] 313109 0
To assess the pharmacodynamics of PF530 compared to Betaferon. Pharmacodynamics will be assessed through collection of blood samples at pre-dose, 3, 6, 12, 24, 36, 48, 60, 72, 96, 120 and 144 hours post dose.

Timepoint [2] 313109 0
Pharmacodynamic blood samples will be collected at pre-dose, 3, 6, 12, 24, 36, 48, 60, 72, 96, 120 and 144 hours post dose.
Secondary outcome [3] 313110 0
To assess the immunogenicity of PF530 compared to Betaferon
Immunogenicity will be assessed through collection of blood samples on Day -1, 7, 21 and 28
Timepoint [3] 313110 0
Immunogenicity blood samples will be collected on Day -1, 7, 21 and 28

Eligibility
Key inclusion criteria
1. Healthy male or female aged 18-50 years
3. Females of childbearing potential must agree to use two effective methods of birth control, practice complete abstinence, or confirm sterilization of monogamous male partner
5. Males must have had a documented vasectomy, practice complete abstinence or use a condom and refrain from sperm.
6. Body Mass Index (BMI) greater than or equal to 18.0 and less than or equal to 30.0 kg/metres squared at Screening.
7. Participant is free from clinically significant illness or disease as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening and Day -1.
8. Able to understand and sign the written Informed Consent Form
9. Willing to follow the protocol requirements and comply with protocol restrictions.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Female subjects who are pregnant or lactating.
2. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, metabolic, psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator.
3. History of clinically significant serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicaemia) less than or equal to 90 days prior to first dose.
4. History of recurring oral herpes virus (cold sores) or presence of oral herpes during Screening or at dosing.
5. History of chronic fatigue syndrome or fibromyalgia.
6. Fever (defined as body temperature greater than or equal to 38.0 degrees Celsius) or symptomatic viral or bacterial infection (including upper respiratory tract infection) less than or equal to 30 days prior to dosing.
7. Previous treatment with any interferon product, including investigational use.
8. Participants with a history of malignant disease, including solid tumours and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
9. A calculated creatinine clearance of less than or equal to 70 mL/min according to the Cockcroft-Gault equation.
10. Positive screening test for human immunodeficiency virus (HIV).
11. Positive screening test for hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis surface antigen [HBsAg] at Screening). Participants with immunity to hepatitis B (defined as negative HBsAg and positive hepatitis B surface antibody [HBsAb]) are eligible to participate in the study.
12. History of epilepsy, seizure disorder or any unexplained black-outs.
13. History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator).
14. Score of greater than or equal to 8 on either the anxiety or depression sub-scales of the Hospital Anxiety and Depression Scale (HADS) at Screening or Day -1
15. Score of greater than or equal to 9 on the Modified Scale for Suicidal Ideation (MSSI) at Screening or Day -1
16. History of hypersensitivity or intolerance to paracetamol or non-steroidal anti-inflammatory drugs (NSAID) that would preclude the use of at least 1 of these during the study.
17. History of severe allergic or anaphylactic reactions or a known allergy to any component of the interferon beta-1b formulation.
18. History of drug or alcohol abuse less than or equal to 12 months prior to Screening.
19. History of tobacco use less than or equal to 6 months prior to Screening.
20. A positive test for drugs of abuse or alcohol during Screening or prior to dosing.
21. Unwilling or unable to abstain from alcohol from 7 days prior to dosing until end-of-study assessments.
22. Use of any prescription medication, over-the-counter medication, or herbal supplements/products during Screening or throughout study, unless approved by both the Principal Investigator and the Sponsor.
23. Clinically significant abnormal clinical laboratory test values, as determined by the Investigator, or any value of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that is above the upper limit of normal, any value of platelets or haemoglobin that is below the lower limit of normal, or any out-of-range value for total white blood cells, serum sodium or potassium. Tests may be repeated once at the discretion of the Investigator.
24. Clinically significant abnormalities in 12-lead ECG.
25. Prior treatment with any investigational drug less than or equal to 30 days prior to dosing (Day 1), or less than or equal to 5 half-lives of the drug (whichever is longer), or current enrolment in any other study treatment or disease study.
26. Vaccinations less than or equal to 30 days prior to dosing.
27. Donation or loss of greater than or equal to 500 mL of blood or plasma within 30 days prior to dosing.
28. Any other reason for which the Principal Investigator considers it is not in the best interest of the participant to undertake the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will occur on Day 1, after all screening procedures have been performed and eligibility for the clinical trial has been confirmed. After randomization has been approved, the randomization assignment will be obtained by the clinical trial site’s unblinded pharmacist or Investigational Product consignee.
Participants will not be assigned to cohorts in the study. Instead, participants will be randomly assigned to either Sequence A (PF530 followed by Betaferon) or Sequence B (Betaferon followed by PF530).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomized to receive either sequence A (PF530 followed by Betaferon) or sequence B (Betaferon followed by PF520) in a 1:1 ratio using a blocked randomisation approach, with no stratification. The randomisation schedule will be generated using SAS v9.4, covering both parts I and II (n=48).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Statistical summaries will be descriptive in nature (e.g., means, standard deviations, and percentiles). All subjects will be grouped according to treatment actually received. With the exception of subject disposition, safety and efficacy summaries will be limited to subjects receiving at least one dose of study treatment.
The PK parameters will be summarised by treatment received. The individual and mean PK concentrations will also be presented graphically. The comparison of PK parameters will be based on a 90% confidence interval for the ratio of the population geometric means (test/reference), in particular Cmax and AUC.
The PD parameters will be summarized by treatment received and presented graphically as needed. If appropriate, the comparison of PD parameters will be based on a 90% confidence interval for the ratio of the population geometric means (test/reference).
All PK and PD endpoints will be analyzed and compared without a pre-specified hierarchical order.

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
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)
SA
Recruitment hospital [1] 3493 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 9261 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 290789 0
Commercial sector/Industry
Name [1] 290789 0
Pfenex Inc
Address [1] 290789 0
10790 Roselle St.
San Diego, CA 92121
Country [1] 290789 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Pfenex Inc
Address
10790 Roselle St.
San Diego, CA 92121
Country
United States of America
Secondary sponsor category [1] 289472 0
None
Name [1] 289472 0
Address [1] 289472 0
Country [1] 289472 0
Other collaborator category [1] 278361 0
Commercial sector/Industry
Name [1] 278361 0
Novotech (Australia) Pty Ltd
Address [1] 278361 0
Level 3, 235 Pyrmont St, Pyrmont, NSW, 2009
Country [1] 278361 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292419 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 292419 0
129 Glen Osmond Road
Eastwood
South Australia 5063
Ethics committee country [1] 292419 0
Australia
Date submitted for ethics approval [1] 292419 0
04/02/2015
Approval date [1] 292419 0
10/03/2015
Ethics approval number [1] 292419 0

Summary
Brief summary
The purpose of this study is to test the safety and tolerability of new interferon beta-1b product called PF530.

Who is it for?
You may be eligible to join this study if you are aged between 18 to 50 years and are in good general health. Females must not be pregnant or breastfeeding.

Study details
The study will consist of two parts (Part I and Part II). Twelve participants will be enrolled in Part I, and the results of this part will determine how many participants will be enrolled in Part II.

The study is divided into a screening phase lasting about 4 weeks and an on-study phase. The on-study phase will be broken into 2 periods with at least a 14 day gap (called a wash-out) between each period to ensure that the study drug is completely gone from your body before the next period starts. Doses will be administered subcutaneously (under the skin), with participants receiving PF530 in one period and BETAFERON in the other period. The order in which you receive those doses (i.e. in period 1 or period 2) will be random. The chance of receiving PF530 first compared to BETAFERON is 1:1. Which treatment you receive first (PF530 or BETAFERON) will not be known by the study staff or yourself. The study dose will be given to you by a clinical unit staff member. Study doses will be administered in the abdomen.
Initially in Part I, the first 2 participants will receive a randomised dose – one with PF530 and one with BETAFERON - on the morning of Day 1 and will complete 48 hours of monitoring by site staff before the remaining participants receive their dose. This is referred to as a sentinel dosing. Dosing of the remaining participants will depend on safety information obtained from the 2 sentinel participants.
Each of the two study periods will include a confinement period of 5 days and 4 nights, commencing the day before your dosing each period. After leaving the clinical unit on Day 4, you will be required to attend the unit at the same time each morning on Days 5, 6 & 7 for a brief appointment.
Your total involvement in the study will be approximately 8 weeks. It is anticipated that each visit will last from 1-2 hours depending on the procedures required. These will include: blood and urine sampling; physical examination; vital signs; medical history, concomitant medications and adverse events (AE) assessment; completion of questionnaires.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55174 0
Dr Sepehr Shakib
Address 55174 0
Royal Adelaide Hospital
North Terrace, Adelaide,
South Australia 5000

Country 55174 0
Australia
Phone 55174 0
+61 8 8222 2763
Fax 55174 0
Email 55174 0
Sepehr.Shakib@health.sa.gov.au
Contact person for public queries
Name 55175 0
Ms Louise Pirc
Address 55175 0
CMAX, A Division of IDT Australia, Limited
Royal Adelaide Hospital
North Terrace, Adelaide,
South Australia 5000

Country 55175 0
Australia
Phone 55175 0
+61 8 8222 3923
Fax 55175 0
Email 55175 0
louise.pirc@cmax.com.au
Contact person for scientific queries
Name 55176 0
Dr Hubert C. Chen
Address 55176 0
Pfenex Inc.
10790 Roselle St.
San Diego, CA 92121
Country 55176 0
United States of America
Phone 55176 0
+1 858 3524358
Fax 55176 0
Email 55176 0
hchen@pfenex.com

No information has been provided regarding IPD availability
Summary results
No Results