Clinical trial NCT01991990: A Pharmacodynamic Study to Evaluate Neutrophil Distribution Kinetics and Function Following Single-Dose RoActemra/Actemra (Tocilizumab) in Healthy Volunteers
Official title: A Single Blind Phase IV Pharmacodynamic Study to Evaluate Neutrophil Distribution Kinetics and Function Following Single-Dose Tocilizumab Treatment in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This Phase IV, single-blind , randomized, two-arm study will explore the pharmacodynamics effects of RoActemra/Actemra (tocilizumab) on neutrophil redistribution, function and survival in healthy subjects. Subjects will receive either a single dose of intravenous (IV) RoActemra/Actemra at a dose of 8 mg/kg over one hour on study Day 0 or placebo. Neutrophil kinetics data will be collected for all subjects up to Day 10 of the study. Following the last study visit on Day 10, all subjects will attend two further safety follow-up visits on Day 28 and Day 56.


Eligibility criteria: Inclusion Criteria:

* Male aged between 18 and 65 years inclusive
* Healthy as determined by screening assessments
* Body mass index (BMI) 18 to 30 kg/m2 inclusive
* Non-smoker
* Must agree to use a barrier method of contraception supplemented with spermicide during the treatment period and for at least 150 days after the last dose of study drug

Exclusion Criteria:

* Participation in a clinical study with an investigational drug within 3 months or at least 5 half-lives (whichever is longer) prior to dosing
* Current or past history of smoking within 6 months
* Previous exposure to therapeutic monoclonal antibodies in the past 6 months prior to screening
* Current or clinically significant history of any condition that, in the opinion of the investigator, would: place the subject at undue risk; invalidate the giving of informed consent; interfere with PK or PD data; or interfere with the ability of the subject to complete the study
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* Any recurrent infections; infection requiring antibiotic treatment in the 6 weeks prior to dosing; mononucleosis in the 6 months prior to dosing; known HIV, Hepatitis B, or Hepatitis C; or active infection at the time of screening
* Active tuberculosis (TB) requiring treatment within the previous 3 years.
* Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years
* Primary or secondary immunodeficiency
* Autoimmune disease
* Use or dependence on substance of abuse
* Alcohol abuse or average weekly intake greater than 2 units per day
* Screening or baseline resting heart rate \< 45 or \>90 beats per minute
* Major surgery within 8 weeks prior to screening
* Major illness in the 3 months prior to dosing
* Biliary obstruction
* Current or past history of diverticulitis

Primary outcomes:
measure: Neutrophil Redistribution Analysis on Day 4 (Neutrophil Nadir)
timeFrame: Day 4
measure: Neutrophil Redistribution Analysis on Day 5
timeFrame: Day 5
measure: Neutrophil Redistribution Analysis on Day 10
timeFrame: Day 10
measure: Neutrophil Phagocytosis: Change From Baseline to Nadir (Day 4) in the Percentage of eFluor670-Positive (eFluoro670+) Neutrophils
timeFrame: Baseline, Day 4
measure: Neutrophil Phagocytosis: Change From Baseline to Nadir (Day 4) in Median Fluorescence Intensity (MFI) of eFluor670+ Neutrophils
timeFrame: Baseline, Day 4
measure: Neutrophil Respiratory Burst: Change From Baseline to Nadir (Day 4) in the Production of Reactive Oxygen Species as Measured by Chemiluminescence (Relative Light Units - Absolute)
timeFrame: Baseline, Day 4
measure: Neutrophil Survival: Change From Baseline to the Nadir (Day 4) in the Percentage of Apoptotic Neutrophils as Measured by Microscopic Morphology
timeFrame: Baseline, Day 4
measure: Neutrophil Survival: Change From Baseline to the Nadir in the Percentage of Apoptotic Neutrophils as Measured by Flow Cytometry
timeFrame: Baseline, Day 4
measure: Neutrophil Morphology: Change From Baseline to Nadir in the Number of Neutrophils With Shape Change Measured Using Flow Cytometry
timeFrame: Baseline, Day 4
measure: Neutrophil Morphology: Change From Baseline to the Nadir (Day 4) in the Percentage of Neutrophils With Shape Change Measured by Flow Cytometry (FSC-High Cells)
timeFrame: Baseline, Day 4
measure: Neutrophil Morphology: Change From Baseline to the Nadir (Day 4) in the Percentage of Neutrophils With Shape Change Measured by Microscopic Morphology
timeFrame: Baseline, Day 4
measure: Absolute Median Fluorescence Intensities of Neutrophil Adhesion Molecules
timeFrame: Day 4
Secondary outcomes:
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: