LeucocytosisPhase 1NCT02762799

Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® Compared to Neupogen®

A Phase 1 study testing Leucostim® and Neupogen® in people with Leucocytosis, run by Biocad.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

BCD-002-1 is 1 phase clinical trial to evaluate pharmacokinetics, pharmacodynamics and safety of single-injection of Leucostim® to healthy volunteers compared to Neupogen® Read more about this study

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Leucocytosis
What is being tested?: Leucostim® and Neupogen®
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: No sites listed yet
Study dates: 18 Jul 2016to 11 Nov 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Written informed consent.
Male gender.
Age between 18 and 45 years.
Normal body mass index.
Verified diagnosis "healthy", established according to the anamnesis, physical examination and laboratory findings.
Absence of alcohol or drug abuse.

Who cannot join

History of use of filgrastim.
Allergy to any components of study drugs.
Acute hemorrhage, donation of blood / plasma or blood transfusions during last 2 months prior to enrollment in the study, history of chronic bleeding.
Surgical interventions during last 30 days prior to screening or planed surgical intervention during the study.
Any diseases that could interfere with pharmacokinetics of filgrastim, including chronic liver, liver or blood diseases, diseases of cardiovascular, lung and neuroendocrine systems.
Fever with body temperature higher than 40°С.

About this study

Official title: Single-center Open Randomized Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® (JSC "BIOCAD", Russia) Compared to Neupogen® (F. Hoffman-La Roche Ltd., Switzerland)

BCD-002-1 is 1 phase clinical trial to evaluate pharmacokinetics, pharmacodynamics and safety of single-injection of Leucostim® to healthy volunteers compared to Neupogen®

Conditions: Leucocytosis
Being tested: Leucostim®, Neupogen®
Keywords: neutrophil count, filgrastim, granulocyte colony-stimulating factor
Medical subject headings: Leukocytosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Leucostim®Biological
Also called filgrastim
Leucostim® is filgrastim biosimilar.
Neupogen®Biological
Also called filgrastim

Study groups in NCT02762799
Study group	Role	What they receive
Leucostim® --> Neupogen®, subcutaneous injections	Experimental	Healthy volunteers in this group will receive single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Receives: Biological: Leucostim®; Biological: Neupogen®
Neupogen® --> Leucostim®, subcutaneous injections	Experimental	Healthy volunteers in this group will receive single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Receives: Biological: Leucostim®; Biological: Neupogen®
Leucostim® --> Neupogen®, intravenous injections	Experimental	Healthy volunteers in this group will receive single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29. Receives: Biological: Leucostim®; Biological: Neupogen®
Neupogen® --> Leucostim®, intravenous injections	Experimental	Healthy volunteers in this group will receive single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29. Receives: Biological: Leucostim®; Biological: Neupogen®

What is being measured

The primary outcome is the main question the study is designed to answer.

AUC (0-48 Hours)
Area Under Curve (AUC) "concentration - time" from the moment of filgrastim injection to 48 hours
Measured: 0 to 48 hours post-dose
Cmax After Subcutaneous Injection
Maximal concentration of filgrastim after subcutaneous injection of filgrastim
Measured: 0 to 48 hours post-dose

Secondary outcomes (15)

Cmax After Intravenous Injection
Maximal concentration of filgrastim after intravenous injection of filgrastim
Measured: 0 to 48 hours post-dose
Tmax After Injection
Time after single injection to reach maximal concentration of filgrastim
Measured: 0 to 48 hours post-dose
Т½
Half-life of filgrastim after single injection of filgrastim
Measured: 0 to 48 hours post-dose
Kel
The elimination rate constant after single injection of filgrastim
Measured: 0 to 48 hours post-dose
Clearance
Clearance of filgrastim after single injection
Measured: 0 to 48 hours post-dose
ANC-AUEC (0-336 Hours)
Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on absolute neutrophil count (ANC)
Measured: 0 to 336 hours post-dose
ANC-Emax
Maximal absolute neutrophil count after single filgrastim injection
Measured: 0 to 336 hours post-dose
CD34-AUEC (0-336 Hours)
Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on CD-34 cells count (CD34)
Measured: 0 to 336 hours post-dose
CD34-Emax
Maximal absolute count of CD34-cells after single filgrastim injection
Measured: 0 to 336 hours post-dose
Overall Frequency of Serious Adverse Events (SAE)
Measured: 0 to 336 hours post-dose
Overall Frequency of Adverse Events (AE)
Measured: 0 to 336 hours post-dose
Frequency of Local Reactions
Measured: 0 to 336 hours post-dose
Frequency of AE/SAE 3-4 Grade CTCAE 4.03
Grading scale of CTCAE 4.03
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE:
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (activities of daily living).
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: 0 to 336 hours post-dose
Frequency of Preliminary Withdrawal Due to AE/SAE
Measured: 0 to 336 hours post-dose
Proportion of Patients With Binding or Neutralizing Antibodies to Filgrastim
Proportion of patients who had developed binding or neutralizing antibodies to filgrastim after single injection.
Measured: 0 to 336 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jul 201611 Nov 2016

First posted5 May 2016 (estimated)
Study start18 Jul 2016
Primary completion11 Nov 2016
Study completion11 Nov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for LeucocytosisStudies of the same condition, open and under way.
More trials run by BiocadThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02762799
Sponsor's protocol ID: BCD-002-1
Status last verified: Dec 2018
First submitted: 1 Apr 2016
Last updated: 19 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Undecided

Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single-center Open Randomized Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® (JSC "BIOCAD", Russia) Compared to Neupogen® (F. Hoffman-La Roche Ltd., Switzerland)
ClinicalTrials.gov ID: NCT02762799
Acronym / sponsor ID: BCD-002-1
Conditions: Leucocytosis
Keywords: neutrophil count, filgrastim, granulocyte colony-stimulating factor
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: BiocadIndustry (pharma, biotech, devices)
Study start: 18 Jul 2016 (actual)
Primary completion: 11 Nov 2016 (actual)
Study completion: 11 Nov 2016 (actual)
First posted: 5 May 2016 (estimated)
Results: Posted 19 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

BCD-002-1 is 1 phase clinical trial to evaluate pharmacokinetics, pharmacodynamics and safety of single-injection of Leucostim® to healthy volunteers compared to Neupogen®

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Leucostim® --> Neupogen®, subcutaneous injections	Experimental	Biological: Leucostim®, Biological: Neupogen®Healthy volunteers in this group will receive single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, subcutaneous injections	Experimental	Biological: Leucostim®, Biological: Neupogen®Healthy volunteers in this group will receive single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Leucostim® --> Neupogen®, intravenous injections	Experimental	Biological: Leucostim®, Biological: Neupogen®Healthy volunteers in this group will receive single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, intravenous injections	Experimental	Biological: Leucostim®, Biological: Neupogen®Healthy volunteers in this group will receive single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29.

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Written informed consent.
Male gender.
Age between 18 and 45 years.
Normal body mass index.
Verified diagnosis "healthy", established according to the anamnesis, physical examination and laboratory findings.

Key exclusion criteria (6 listed)

History of use of filgrastim.
Allergy to any components of study drugs.
Acute hemorrhage, donation of blood / plasma or blood transfusions during last 2 months prior to enrollment in the study, history of chronic bleeding.
Surgical interventions during last 30 days prior to screening or planed surgical intervention during the study.
Any diseases that could interfere with pharmacokinetics of filgrastim, including chronic liver, liver or blood diseases, diseases of cardiovascular, lung and neuroendocrine systems.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Leucostim®Also: filgrastimLeucostim® is filgrastim biosimilar.	Biological	Leucostim® --> Neupogen®, intravenous injections, Leucostim® --> Neupogen®, subcutaneous injections, Neupogen® --> Leucostim®, intravenous injections, Neupogen® --> Leucostim®, subcutaneous injections
Neupogen®Also: filgrastim	Biological	Leucostim® --> Neupogen®, intravenous injections, Leucostim® --> Neupogen®, subcutaneous injections, Neupogen® --> Leucostim®, intravenous injections, Neupogen® --> Leucostim®, subcutaneous injections

Primary outcome

AUC (0-48 Hours)
Time frame: 0 to 48 hours post-dose
Area Under Curve (AUC) "concentration - time" from the moment of filgrastim injection to 48 hours
Cmax After Subcutaneous Injection
Time frame: 0 to 48 hours post-dose
Maximal concentration of filgrastim after subcutaneous injection of filgrastim

15 secondary outcomes

Cmax After Intravenous Injection
Time frame: 0 to 48 hours post-dose
Tmax After Injection
Time frame: 0 to 48 hours post-dose
Т½
Time frame: 0 to 48 hours post-dose
Kel
Time frame: 0 to 48 hours post-dose
Clearance
Time frame: 0 to 48 hours post-dose
ANC-AUEC (0-336 Hours)
Time frame: 0 to 336 hours post-dose
ANC-Emax
Time frame: 0 to 336 hours post-dose
CD34-AUEC (0-336 Hours)
Time frame: 0 to 336 hours post-dose
CD34-Emax
Time frame: 0 to 336 hours post-dose
Overall Frequency of Serious Adverse Events (SAE)
Time frame: 0 to 336 hours post-dose
Overall Frequency of Adverse Events (AE)
Time frame: 0 to 336 hours post-dose
Frequency of Local Reactions
Time frame: 0 to 336 hours post-dose
Frequency of AE/SAE 3-4 Grade CTCAE 4.03
Time frame: 0 to 336 hours post-dose
Frequency of Preliminary Withdrawal Due to AE/SAE
Time frame: 0 to 336 hours post-dose
Proportion of Patients With Binding or Neutralizing Antibodies to Filgrastim
Time frame: 0 to 336 hours post-dose

Results and safety

Results posted to the registry on 19 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Leucostim® --> Neupogen®, Subcutaneous Injections	18	18
Neupogen® --> Leucostim®, Subcutaneous Injections	18	18
Leucostim® --> Neupogen®, Intravenous Injections	12	11
Neupogen® --> Leucostim®, Intravenous Injections	12	12

Primary outcome: AUC (0-48 Hours)

Time frame: 0 to 48 hours post-dose. Geometric mean (Standard Deviation). Unit: picogram per ml / hour

Measure	Leucostim® Subcutaneous Injections n = 36	Neupogen® Subcutaneous Injections n = 36	Leucostim® Intravenous Injections n = 24	Neupogen® Intravenous Injections n = 24
Value	168603.588 (47721.48)	181152 (54706.439)	411826.811 (204285.095)	427355.99 (170878.6)

Primary outcome: Cmax After Subcutaneous Injection

Time frame: 0 to 48 hours post-dose. Geometric mean (Standard Deviation). Unit: picogram per ml

Measure	Leucostim® Subcutaneous Injections n = 36	Neupogen® Subcutaneous Injections n = 36
Value	21605.163 (5247.467)	23389.559 (7549.536)

15 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Leucostim®, Subcutaneous Injections	0 of 36 (0%)	36 of 36 (100%)	0 of 36
Neupogen® Subcutaneous Injections	0 of 36 (0%)	35 of 36 (97.2%)	0 of 36
Leucostim®, Intravenous Injections	0 of 24 (0%)	22 of 24 (91.7%)	0 of 24
Neupogen®, Intravenous Injections	0 of 23 (0%)	22 of 23 (95.7%)	0 of 23

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roman Ivanov, PhD study chair

JCS BIOCAD

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Leucostim® and Neupogen® in people with Leucocytosis, run by Biocad.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC (0-48 Hours) (time frame: 0 to 48 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02762799.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.