E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
healthy volunteers (intended indication: Rheumatoid Arthritis)
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis (RA) in adults. RA is a long-term disease that leads to inflammation of the joints and surrounding tissues. It can also affect other organs. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
PD objectives:
To characterize the effects of TCZ on the following neutrophil tests in all healthy subjects. Relevant comparisons will be made between TCZ-treated and non-treated subjects and also any differences between TCZ-treated neutropenic (Grade 3/4) and non-neutropenic subjects:
- Neutrophil redistribution following 111Indium labeling
- Neutrophil morphology
- Neutrophil function
- Neutrophil survival
- Expression of neutrophil adhesion molecules
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E.2.2 | Secondary objectives of the trial |
- To monitor safety and tolerability as part of addressing the PD objectives
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male aged between 18 and 65 years inclusive
- Healthy as determined by screening assessments
- Body Mass Index between 18 kg/m2 and 302 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
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Neutrophil redistribution following 111Indium labelling
2) Neutrophil morphology
3) Neutrophil function
4) Neutrophil survival
5) Expression of neutrophil adhesion molecules |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Safety: Incidence of adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date when the last subject, last visit (LSLV) occurs or if the Sponsor decides to discontinue the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 20 |