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TerminatedNCT03029000GRANIXUpdated Dec 13, 2022Results posted

Study of the Effect of a 5-Day Regimen of Study Drug on Peripheral Stem Cell Mobilization in Healthy Participants

A Phase 3 interventional study of Tbo-filgrastim in Healthy Participants, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Terminated at 9 sites in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-12-13.

Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 3, Interventional, and Treatment

Why this study was terminated
Study was terminated due to low enrollment
Phase
Phase 3
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
18 Years to 60 Years
Sex
All
01

Study summary

A multi-center, open-label, single-arm clinical study to assess effects of a 5-day regimen of 10 micrograms per kilogram (mcg/kg) of tbo-filgrastim administered subcutaneously daily on the mobilization of cluster of differentiation 34+ (CD34+) cells in at least 60 healthy male and female participants. The pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity of tbo-filgrastim will be assessed.

02

Conditions studied

  • Healthy Participants
03

In context

Lead sponsor

Teva Branded Pharmaceutical Products R&D, Inc. is the lead sponsor of 205 studies on the registry; none are open to participants now.

Of its 49 completed or terminated interventional studies of FDA-regulated products, 47 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Written informed consent is obtained from the participant
  • The participant has a body weight of at least 50 kilograms (kg)
  • The participant has a body mass index (BMI) of more than 18.5 and less than 35.0 kilograms per square meter (kg/m\^2)
  • The participant is in good health as determined by medical and psychiatric history, physical examination, electrocardiogram (ECG) recordings, serum chemistry, hematology, coagulation, urinalysis, and serology
  • Women may be included only if they have a negative beta human chorionic gonadotropin (beta-hCG) test at baseline, are sterile (defined as documented hysterectomy, bilateral oophorectomy or bilateral salpingectomy, or congenitally sterile), or postmenopausal (defined as no menses for 12 months without alternative medical cause and increased follicle stimulating hormone [FSH] of above 35 units per liter [U/L] in women not using hormonal contraception or hormonal replacement therapy). Women of childbearing potential whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study and for 30 days after the last tbo-filgrastim administration
  • The participant has a negative alcohol urine test and a negative urine drug screen
  • The participant must be willing and able to comply with study restrictions
  • The participant is human leukocyte antigen (HLA) -matched or haploidentical-related to the recipient

Exclusion criteria

Exclusion Criteria:

  • The participant currently has or had a history of any clinically relevant gastrointestinal, hematologic, respiratory, psychiatric, renal, hepatic, cardiac, metabolic (such as, fructose intolerance), neurological, or any other disease or condition which may influence the physiological metabolic turnover (such as, severe endocrine diseases, febrile condition, severe infections), which may interfere with the study objectives, or which could expose the participant to undue risk through the participation in the clinical study
  • The participant has had: (1) a trauma or surgery in the past 2 months; (2) a clinically relevant illness within 4 weeks before the first dose of tbo-filgrastim; (3) any acute illness within 1 week before the first dose of tbo-filgrastim; or (4) symptoms of any clinically relevant or acute illness at baseline
  • The participant has existence or recent history of persistent pulmonary infiltrates, recent pneumonia, recent bronchitis, recurrent lung infections, or history or evidence of any lung disease including asthma, or current symptoms of upper respiratory tract infection. In the case of pneumonia, participant may be screened 12 weeks after cessation of antibiotic treatment
  • The participant has findings of splenomegaly on sonography at screening, defined by length of spleen more than 12.3 centimeters (cm) and clinical judgment
  • The participant has a history of malignancy, including hematologic malignancy, except for appropriately treated non-melanoma skin carcinoma in the last 5 years
  • The participant has a clinically significant deviation from normal in ECG recordings or physical examination findings, as determined by the investigator
  • The participant is pregnant or lactating, or was pregnant in the previous 6 months, or intends to get pregnant during the study or within 30 days after the last dose of study drug
  • The participant has habitually consumed, within the last 2 years, more than 21 units of alcohol per week, or has a history or evidence of alcohol, narcotic, or any other substance abuse as defined by the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-V, American Psychiatric Association 2013). Note: A unit of alcohol is equal to 1 ounce (29.6 milliliters [mL]) of hard liquor, 5 ounces (148 mL) of wine, or 8 ounces (236.8 mL) of beer
  • The participant has taken any of the following investigational medicinal products (IMPs), medicinal products, or substances:

    1. Any IMP within 30 days or 5 half-lives (whichever is longer) before the first dose of tbo-filgrastim, or in the case of a new chemical entity, 3 months or 5 half-lives (whichever is longer) before the first dose of tbo-filgrastim
    2. Known history of treatment with blood-cell colony-stimulating factors
    3. Current or recent (within 4 weeks) treatment with lithium
  • The participant has donated plasma within 7 days before screening or has donated blood within 56 days before screening
  • The participant has a documented or self-reported history of tuberculosis or recent travel to countries of endemic disease (last 8 weeks)
  • The participant has 1 or more clinical laboratory test value(s) outside the range specified below, or any other clinically significant laboratory abnormality as determined by the investigator or medical monitor:

    1. Hemoglobin less than or equal to (\<=) 12.5 grams per deciliter (g/dL) (women) and hemoglobin \<=13.5 g/dL (men)
    2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values of greater than (>) 3 * the upper limit of the normal range (ULN)
    3. Total bilirubin of >2 * ULN
    4. Findings of cholestasis (eg, abnormal values of alkaline phosphatase)
  • The participant has a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen, antibodies to hepatitis C virus, immunoglobulin M (IgM) antibodies to cytomegalovirus, human T-lymphotropic virus, West Nile virus, malaria, or syphilis
  • The participant has a documented or self-reported history of tuberculosis or recent travel to countries of endemic disease (last 8 weeks)
  • The participant has, after resting for 5 minutes, increased blood pressure (BP) (defined as systolic BP in seated position of more than 145 millimeters of mercury [mm Hg] or diastolic BP in seated position of more than 95 mm Hg), or low BP (defined as systolic BP in seated position of less than 90 mm Hg or diastolic BP in seated position of less than 45 mm Hg) (Only 2 rechecks of the participant's BP are permitted for eligibility purposes)
  • The participant has, after resting for 5 minutes, a pulse in seated position of less than 45 or more than 90 beats per minute (Only 2 rechecks of the participant's pulse are permitted for eligibility purposes)
  • The participant is unwilling to refrain from vigorous exercise (eg, strenuous or unaccustomed weight lifting, running, bicycling) from 72 hours before Day 1 until Day 15
  • The participant is unlikely to comply with the study protocol or is unsuitable for any other reasons, as judged by the investigator
  • The participant has a history of autoimmune disease, including rheumatic diseases and thyroid disorders
  • The participant has a history of deep vein thrombosis or pulmonary embolism
  • The participant has thrombocytopenia defined as platelet count \<150 * 109 cells per liter (cells/L) at screening or at baseline
  • The participant has a history of bleeding problems (eg, hemophilia, thrombocytopenia, idiopathic thrombocytopenic purpura, clotting factor deficiencies or disorders)
  • The participant has positive hemoglobin-solubility test
  • The participant has a history of iritis or episcleritis
  • The participant has a history of significant hypersensitivity, intolerance, or allergy to tbo-filgrastim or any other E. coli derived product or excipient, or other medicinal product, food, or substance, unless approved by the investigator
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Tbo-filgrastim (GRANIX)

    Participants will receive tbo-filgrastim 10 mcg/kg of body weight, subcutaneously on the morning of Days 1 to 5. The actual dose of tbo-filgrastim administered to each, individual participant will be calculated at baseline according to his or her body weight and that specific dose (10 mcg/kg of body weight) for each, individual participant will remain the same for all consecutive daily doses. If the collection goal will not meet after the first apheresis on Day 5, tbo-filgrastim 10 mcg/kg of body weight will be administered subcutaneously for up to 3 additional days (Days 6 to 8) followed by daily apheresis to reach the cumulative collection goal.

    Drug: Tbo-filgrastim

Interventions

  • DrugTbo-filgrastim

    solution for subcutaneous injection

    Also known as: XM02

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With at Least 2*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) of Recipient Body Weight Collected in the First Apheresis on Day 5

    The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

    Time frame: Day 5

Secondary outcomes

  1. Percentage of Participants With at Least 2*10^6 CD34+ Cells/kg of Donor Baseline Body Weight Collected After the First Apheresis on Day 5

    The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

    Time frame: Day 5

  2. Percentage of Participants With at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight Collected After the First Apheresis on Day 5

    The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

    Time frame: Day 5

  3. Number of Aphereses Necessary to Collect at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight

    The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

    Time frame: Days 5 to 8

  4. Percentage of Participants With Adverse Events (AEs)

    A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs presented here included both SAEs and non-serious AEs.

    Time frame: From first administration of study drug (Day 1) up to early termination/end of study (up to approximately 3 months)

  5. Percentage of Participants With Anti-Drug Antibodies (ADA)

    Blood samples (5 milliliters \[mL\]) for analysis of ADA were obtained for all participants at timepoints described.

    Time frame: Baseline (Day -3) up to early termination/end of study (up to approximately 3 months)

  6. Maximum Observed Serum Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor (r-metHuG-CSF) Concentration (Cmax)

    Blood samples were drawn for all participants for the determination of serum r-metHuG-CSF concentrations on Day 4. Pharmacokinetic (PK) parameter was calculated from concentration-time data using non compartmental methods, when possible.

    Time frame: Day 4 (8 hours post-dose)

  7. Maximum Observed Peripheral CD34+ Cell Count (CD34+Cmax)

    Serial blood samples for the determination of CD34+ cell count were drawn.

    Time frame: Between Day 1 (pre-dose) and before the first apheresis on Day 5

07

Results

Posted Dec 14, 2018
Limitations and caveats
The study was terminated early due to operational feasibility. The decision to terminate the study was not related to any new or emerging safety concerns.

Participant flow

Participant flow — Overall Study
MilestoneTbo-Filgrastim (GRANIX)
Started1
Completed1
Not completed0

Outcome measures

PrimaryPercentage of Participants With at Least 2*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) of Recipient Body Weight Collected in the First Apheresis on Day 5

The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

Time frame:
Day 5
Reported as:
Number · percentage of participants
Percentage of Participants With at Least 2*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) of Recipient Body Weight Collected in the First Apheresis on Day 5
percentage of participantsTbo-Filgrastim (GRANIX)
Percentage of Participants With at Least 2*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) of Recipient Body Weight Collected in the First Apheresis on Day 5100
SecondaryPercentage of Participants With at Least 2*10^6 CD34+ Cells/kg of Donor Baseline Body Weight Collected After the First Apheresis on Day 5

The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

Time frame:
Day 5
Reported as:
Number · percentage of participants
Percentage of Participants With at Least 2*10^6 CD34+ Cells/kg of Donor Baseline Body Weight Collected After the First Apheresis on Day 5
percentage of participantsTbo-Filgrastim (GRANIX)
Percentage of Participants With at Least 2*10^6 CD34+ Cells/kg of Donor Baseline Body Weight Collected After the First Apheresis on Day 5100
SecondaryPercentage of Participants With at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight Collected After the First Apheresis on Day 5

The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

Time frame:
Day 5
Reported as:
Number · percentage of participants
Percentage of Participants With at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight Collected After the First Apheresis on Day 5
percentage of participantsTbo-Filgrastim (GRANIX)
Percentage of Participants With at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight Collected After the First Apheresis on Day 5100
SecondaryNumber of Aphereses Necessary to Collect at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight

The measurement of CD34+ cells in the apheresis product was performed by the local laboratory according to institutional guidelines.

Time frame:
Days 5 to 8
Reported as:
Number · aphereses
Number of Aphereses Necessary to Collect at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight
apheresesTbo-Filgrastim (GRANIX)
Number of Aphereses Necessary to Collect at Least 5*10^6 CD34+ Cells/kg of Recipient Body Weight1
SecondaryPercentage of Participants With Adverse Events (AEs)

A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs presented here included both SAEs and non-serious AEs.

Time frame:
From first administration of study drug (Day 1) up to early termination/end of study (up to approximately 3 months)
Reported as:
Number · percentage of particicpants
Percentage of Participants With Adverse Events (AEs)
percentage of particicpantsTbo-Filgrastim (GRANIX)
Percentage of Participants With Adverse Events (AEs)100
SecondaryPercentage of Participants With Anti-Drug Antibodies (ADA)

Blood samples (5 milliliters \[mL\]) for analysis of ADA were obtained for all participants at timepoints described.

Time frame:
Baseline (Day -3) up to early termination/end of study (up to approximately 3 months)
Reported as:
Number · percentage of participants
Percentage of Participants With Anti-Drug Antibodies (ADA)
percentage of participantsTbo-Filgrastim (GRANIX)
Percentage of Participants With Anti-Drug Antibodies (ADA)0
SecondaryMaximum Observed Serum Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor (r-metHuG-CSF) Concentration (Cmax)

Blood samples were drawn for all participants for the determination of serum r-metHuG-CSF concentrations on Day 4. Pharmacokinetic (PK) parameter was calculated from concentration-time data using non compartmental methods, when possible.

Time frame:
Day 4 (8 hours post-dose)
Reported as:
Mean · picograms per milliliter (pg/mL)
Maximum Observed Serum Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor (r-metHuG-CSF) Concentration (Cmax)
picograms per milliliter (pg/mL)Tbo-Filgrastim (GRANIX)
Maximum Observed Serum Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor (r-metHuG-CSF) Concentration (Cmax)19912.8
SecondaryMaximum Observed Peripheral CD34+ Cell Count (CD34+Cmax)

Serial blood samples for the determination of CD34+ cell count were drawn.

Time frame:
Between Day 1 (pre-dose) and before the first apheresis on Day 5
Reported as:
Number · cells per microliter (cells/mcL)
Maximum Observed Peripheral CD34+ Cell Count (CD34+Cmax)
cells per microliter (cells/mcL)Tbo-Filgrastim (GRANIX)
Maximum Observed Peripheral CD34+ Cell Count (CD34+Cmax)144

Adverse events

Collected over From first administration of study drug (Day 1) up to early termination/end of study (up to approximately 3 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tbo-Filgrastim (GRANIX)0/1 (0%)0/1 (0%)1/1 (100%)
Most frequent other events
Most frequent other events
EventTbo-Filgrastim (GRANIX)
PainGeneral disorders1/1
Bone painMusculoskeletal and connective tissue disorders1/1
NasopharyngitisInfections and infestations1/1
HeadacheNervous system disorders1/1
NauseaGastrointestinal disorders1/1
DysuriaRenal and urinary disorders1/1
Urinary tract infectionInfections and infestations1/1

Baseline characteristics

All enrolled donor participants, regardless of whether or not a participant was administered tbo-filgrastim.

Age, Categorical
Age, Categorical(Participants)Tbo-Filgrastim (GRANIX)
<=18 years0
Between 18 and 65 years1
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Tbo-Filgrastim (GRANIX)
Female1
Male0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Tbo-Filgrastim (GRANIX)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White1
More than one race0
Unknown or Not Reported0
08

Study locations

9 sites
  • Teva Investigational Site 14029
    Duarte, California 91010, United States
  • Teva Investigational Site 14025
    La Jolla, California 92037-1027, United States
  • Teva Investigational Site 14023
    Beech Grove, Indiana 46107, United States
  • Teva Investigational Site 14026
    Detroit, Michigan 48201, United States
  • Teva Investigational Site 14027
    Chapel Hill, North Carolina 27514, United States
  • Teva Investigational Site 14030
    Cincinnati, Ohio 45242, United States
  • Teva Investigational Site 14033
    Greenville, South Carolina 29615, United States
  • Teva Investigational Site 14035
    Memphis, Tennessee 38120, United States
  • Teva Investigational Site 14024
    San Antonio, Texas 78229, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · May 12, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 13, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03029000
Lead sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Responsible party
Sponsor
First posted
Jan 23, 2017
Start date
Aug 2, 2017
Primary completion
Oct 30, 2017
Completion
Oct 30, 2017
Results posted
Dec 14, 2018
Last update
Dec 13, 2022

Study contacts

Teva Medical Expert, MD
study director · Teva Branded Pharmaceutical Products R&D, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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