Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619001062112
Ethics application status
Approved
Date submitted
12/07/2019
Date registered
30/07/2019
Date last updated
4/08/2020
Date data sharing statement initially provided
30/07/2019
Date results information initially provided
4/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the biosimilarity of SBS6002 to Neulasta when administered to healthy participants
Scientific title
A Phase 1, Bioequivalence Trial Evaluating the Pharmacokinetic and Pharmacodynamic Biosimilarity of SBS6002 Versus Neulasta® Following Subcutaneous Administration to Healthy Volunteers
Secondary ID [1] 296879 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neutropenia 310811 0
Condition category
Condition code
Inflammatory and Immune System 309483 309483 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomized to one of two possible sequences:
Sequence 1: Single dose of 6 mg of SBS6002 (0.6 mL of 10 mg/mL pegfilgrastim solution, based on protein content only) via subcutaneous injection administered on the abdomen, followed by a washout period (of at least 42 days since dose of SBS6002), and a single dose of 6 mg of comparator via subcutaneous injection administered on the abdomen.
Sequence 2: Single dose of 6 mg of comparator via subcutaneous injection administered on the abdomen, followed by a washout period (of at least 42 days since dose of comparator), and a single dose of 6 mg of SBS6002 (0.6 mL of 10 mg/mL pegfilgrastim solution, based on protein content only) via subcutaneous injection administered on the abdomen.
Intervention code [1] 313155 0
Treatment: Drugs
Comparator / control treatment
6 mg of Neulasta (0.6 mL of 10 mg/mL pegfilgrastim solution, based on protein content only) administered via subcutaneous injection
Control group
Active

Outcomes
Primary outcome [1] 308443 0
To determine PK parameters after a single 6 mg dose of SBS6002 is administered to healthy volunteer subjects. PK parameters determined are to include C(max), AUC(0-t), AUC(0-inf), Residual area, T(max), T(1/2 el), K(el), CL/F, and V(d)/F.
Timepoint [1] 308443 0
18 blood samples will be drawn for PK analysis during the treatment period at: pre-dose, 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), and 336 (Day 15) hours post-dose.
Primary outcome [2] 308444 0
To assess PD parameters for Absolute Neutrophil Count (ANC) determination after a single 6 mg dose of SBS6002 is administered to healthy volunteer subjects. PD parameters for ANC determination are to include AUEC(0-t), E(max) and T(max,E).
Timepoint [2] 308444 0
15 blood samples will be drawn for ANC determination at: pre-dose, 4, 8, 16, 24, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), and 336 (Day 15), 504 (Day 22), and 672 (Day 29) hours post-dose.
Primary outcome [3] 308445 0
To assess PD parameters for CD34+ determination after a single 6 mg dose of SBS6002 is administered to healthy volunteer subjects. PD parameters for CD34+ determination are to include AUEC(0-t), E(max) and T(max,E).
Timepoint [3] 308445 0
12 blood samples will be drawn for CD34+ determination at: pre-dose, 24, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), 336 (Day 15), 504 (Day 22), and 672 (Day 29) hours post-dose.
Secondary outcome [1] 354977 0
Primary outcome [4]
To assess the safety and tolerability after a single 6 mg dose of SBS6002 is administered to healthy volunteer subjects. Safety and tolerability will be assessed by observation of the incidence, severity, causality and seriousness of adverse events (related side effects may include fever, diarrhea, shortness of breath, rash, hair loss, numbness, nosebleeds, headache, and pain); vital signs (blood pressure, heart rate, and oral temperature); laboratory tests (drug and alcohol screening, hematology and coagulation, and biochemistry); injection site evaluation; and medical surveillance by clinical site staff.
Timepoint [1] 354977 0
Primary timepoint [4]
Safety and tolerability information will be recorded from the first date of admission to the study unit for a period of 42 days following administration of the last study drug in the assigned sequence. Participant assessments will be taken at the screening visit, as well as during participant confinement to the clinical site (Day -1 to Day 3), and on follow-up visits on Days 4, 5, 6, 8, 10, 12, 15, 22 and 29.
Secondary outcome [2] 354978 0
Primary outcome [5]
To assess immunogenicity via anti-drug antibody (ADA) titre in blood test after a single 6 mg dose of SBS6002 is administered to healthy volunteer subjects.
Timepoint [2] 354978 0
Primary timepoint [5]
3 blood samples will be drawn for anti-drug antibody (ADA) detection at: pre-dose, Day 8, and Day 29 post-dose.
Secondary outcome [3] 372745 0
To determine PK parameters after a single 6 mg dose of Neulasta® is administered to healthy volunteer subjects. PK parameters determined are to include C(max), AUC(0-t), AUC(0-inf), Residual area, T(max), T(1/2 el), K(el), CL/F, and V(d)/F.
Timepoint [3] 372745 0
18 blood samples will be drawn for PK analysis during the treatment period at: pre-dose, 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), and 336 (Day 15) hours post-dose.
Secondary outcome [4] 372746 0
To assess PD parameters for Absolute Neutrophil Count (ANC) determination after a single 6 mg dose of Neulasta® is administered to healthy volunteer subjects. PD parameters for ANC determination are to include AUEC(0-t), E(max) and T(max,E).
Timepoint [4] 372746 0
15 blood samples will be drawn for ANC determination at: pre-dose, 4, 8, 16, 24, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), and 336 (Day 15), 504 (Day 22), and 672 (Day 29) hours post-dose.
Secondary outcome [5] 372747 0
To assess PD parameters for CD34+ determination after a single 6 mg dose of Neulasta® is administered to healthy volunteer subjects. PD parameters for CD34+ determination are to include AUEC(0-t), E(max) and T(max,E).
Timepoint [5] 372747 0
12 blood samples will be drawn for CD34+ determination at: pre-dose, 24, 48, 72 (Day 4), 96 (Day 5), 120 (Day 6), 168 (Day 8), 216 (Day 10), 264 (Day 12), 336 (Day 15), 504 (Day 22), and 672 (Day 29) hours post-dose.
Secondary outcome [6] 372748 0
To assess the safety and tolerability after a single 6 mg dose of Neulasta® is administered to healthy volunteer subjects. Safety and tolerability will be assessed by observation of the incidence, severity, causality and seriousness of adverse events (related side effects may include fever, diarrhea, shortness of breath, rash, hair loss, numbness, nosebleeds, headache, and pain); vital signs (blood pressure, heart rate, and oral temperature); laboratory tests (drug and alcohol screening, hematology and coagulation, and biochemistry); injection site evaluation; and medical surveillance by clinical site staff.
Timepoint [6] 372748 0
Safety and tolerability information will be recorded from the first date of admission to the study unit for a period of 42 days following administration of the last study drug in the assigned sequence. Participant assessments will be taken at the screening visit, as well as during participant confinement to the clinical site (Day -1 to Day 3), and on follow-up visits on Days 4, 5, 6, 8, 10, 12, 15, 22 and 29.
Secondary outcome [7] 372749 0
To assess immunogenicity via anti-drug antibody (ADA) after a single 6 mg dose of Neulasta® is administered to healthy volunteer subjects.
Timepoint [7] 372749 0
3 blood samples will be drawn for anti-drug antibody (ADA) detection at: pre-dose, Day 8, and Day 29 post-dose.

Eligibility
Key inclusion criteria
Subjects enrolled in this study will be members of the community at large. The recruitment advertisements may use various media types. Subjects must meet all of the following criteria to be included in the study:
1) Male, non-smoker or social smoker.
2) Healthy as defined by:
a) the absence of clinically significant illness and surgery within 4 weeks prior to dosing. Inclusion pre-dosing is at the discretion of the Investigator.
b) the absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
c) absence of febrile or infectious illness within 1 week prior to dosing.
3) Provide signed written informed consent prior to the initiation of any study-specific procedures.
4) Willing and able to comply with the requirements of the protocol and be available for the planned duration of the trial.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects to whom any of the following applies will be excluded from the study:
1) Any clinically significant abnormality at physical examination at screening or on Day -1 of Period 1
2) Any clinically significant abnormal hematology, biochemistry and other laboratory test results found at screening.
3) Positive test for hepatitis B, hepatitis C, or HIV at screening.
4) Positive urine drug screen at screening or on Day -1 of Period 1.
5) History of allergic reactions or hypersensitivity to pegfilgrastim, filgrastim, E. coli-derived proteins, PEGylated proteins, or to any excipients of the study drug.
6) Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.
7) Clinically significant ECG abnormalities or vital sign abnormalities at screening.
8) History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening or positive alcohol test at screening or on Day -1 of Period 1.
9) History of significant drug abuse within one year prior to screening or use of soft drugs within 3 months prior to the screening visit or hard drugs within 1 year prior to screening.
10) Participation in any other investigational clinical study in which administration of an investigational study drug occurred within 30 days or 5 half-lives of the product (whichever is the longest) prior to screening.
11) Use of medication, other than topical products without significant systemic absorption.
12) Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
13) Any past exposure to recombinant human G-CSF products and/or a known history of prior treatment with blood-cell colony stimulating factors, interleukins or interferons.
14) History of sickle cell trait or sickle cell disease.
15) History of pulmonary infiltrate or pneumonia within 6 months before the screening visit.
16) Signs or symptoms of chronic obstructive pulmonary disease.
17) Splenomegaly at screening or prior to Day 1.
18) Hereditary fructose intolerance.
19) Tattoos covering the potential study drug injection site.

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)
Allocation involves contacting the holder of the allocation schedule who is the onsite pharmacist with no contact to participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e. computerized sequence generation)
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
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
Statistical Analysis will be performed using mixed procedures in SAS v9.3 (SAS Institute, Cary, USA), ANOVA. Statistical analysis will be performed in reference to each individual receiving treatment, and may be used to make comparisons between doses of study drug and comparator. Demographic parameters will be summarized descriptively. Safety, tolerability and immunogenicity data will be reported using descriptive statistics (arithmetic mean, SD, CV%, Min, Max, and median).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/11/2019
Actual
9/10/2019
Date of last participant enrolment
Anticipated
Actual
18/03/2020
Date of last data collection
Anticipated
Actual
15/04/2020
Sample size
Target
150
Accrual to date
Final
150
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14034 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 26824 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 301450 0
University
Name [1] 301450 0
Mahidol University
Country [1] 301450 0
Thailand
Primary sponsor type
Commercial sector/Industry
Name
INC Research Australia Pty Ltd
Address
159 Port Road, Hindmarsh
SA 5007, Adelaide
Country
Australia
Secondary sponsor category [1] 301140 0
None
Name [1] 301140 0
Address [1] 301140 0
Country [1] 301140 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302183 0
Bellberry Limited HREC (EC00372)
Ethics committee address [1] 302183 0
129 Glen Osmond Road,
Eastwood SA 5063
Ethics committee country [1] 302183 0
Australia
Date submitted for ethics approval [1] 302183 0
24/07/2019
Approval date [1] 302183 0
02/09/2019
Ethics approval number [1] 302183 0

Summary
Brief summary
This research project is being conducted to evaluate the bioequivalence and biosimilarity of SBS6002 to Neulasta when administered to healthy participants by comparing PK, PD, safety and tolerability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89402 0
Dr Kristi Mclendon
Address 89402 0
Q-Pharm
300c Herston Road
Herston QLD 4006
Country 89402 0
Australia
Phone 89402 0
+61 7 3707 2700
Fax 89402 0
+61 7 3845 3637
Email 89402 0
[email protected]
Contact person for public queries
Name 89403 0
Ms Vicki Rossi
Address 89403 0
Q-Pharm
300c Herston Road
Herston QLD 4006
Country 89403 0
Australia
Phone 89403 0
+61 7 3845 3637
Fax 89403 0
Email 89403 0
[email protected]
Contact person for scientific queries
Name 89404 0
Dr Kristi Mclendon
Address 89404 0
Q-Pharm
300c Herston Road
Herston QLD 4006
Country 89404 0
Australia
Phone 89404 0
+61 7 3707 2700
Fax 89404 0
+61 7 3845 3637
Email 89404 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is a Phase 1 study, only aggregate data may be posted/published


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.