E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe stage of Chronic Obstructive Pulmonary Disease (COPD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
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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 |
To evaluate efficacy of ofatumumab in decreasing inflammation in COPD assessed by bronchial biopsies.
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of ofatumumab in patients with COPD and to describe changes in inflammatory mediators in induced sputum, serum and BAL (in a sub-population of patients). To describe objective and subjective changes following treatment with ofatumumab.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients must have a diagnosis of COPD previously diagnosed by a physician (typical history, physical examination and spirometry) with persistent airway obstruction with FEV1/FVC < 70% 2) Male and Female 3) Age ≥ 50 years 4) Former smokers since a minimum of 1 year and a maximum of 6 years having smoked ≥ 15 cigarettes per day ≥ 20 years (15 pack-years) 5) GOLD stage 3 (FEV1/FVC < 70%, 30% ≤ FEV1 < 50% predicted) 6) Systemic steroid < 7.5 mg prednisolone daily during the last 4 weeks prior to screening 7) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
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E.4 | Principal exclusion criteria |
1) Patients previously treated with ofatumumab 2) Resting transcutaneous oxygen saturation < 90% 3) Patients reversible on beta2 stimulating treatment (> 400 ml increase in FEV1) 4) Patients in long term home oxygen therapy (LTOT) 5) Exacerbation within the last 4 weeks prior to screening 6) Influenza vaccination within the last 4 weeks prior to screening 7) Patient currently participating in a pulmonary rehabilitation course 8) Past or current malignancy within the past 5 years except adequately treated: - Cervical carcinoma Stage 1B or less - Non-invasive basal cell and squamous cell skin carcinoma - Malignant melanoma with a complete response of a duration of > 10 years - Other cancer diagnoses with a complete response of a duration of > 5 years
9) Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, sinusitis, and tuberculosis
10) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
11) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
12)History of significant cerebrovascular disease 13)Known HIV positive 14)Known hepatitis B or hepatitis C infection or positive titer 15)Screening laboratory values: - WBC < 3.0x109/L - Neutrophils < 1.5 x109/L - Platelets < 75 x109/L - ALAT > 2.5 times the upper limit of normal - ALP > 2.5 times the upper limit of normal - Bilirubin > 1.5 times the upper limit of normal - Creatinine > 1.5 the upper limit of normal.
16) Previous or current atopic disease such as hay fever, asthma, atopic dermatitis 17)Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening)
18) Current participation in any other interventional clinical study 19) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
20) Breast feeding women or women with a positive pregnancy test at Visit 1 21) Women of childbearing potential (Women are considered of childbearing potential unless they have been hysterectomized, have undergone tubal ligation within at least one year prior to Visit 1, or have been postmenopausal for at least one year) not willing to use adequate contraception as hormonal birth control or intrauterine device for the entire trial period during study and one year after last dose of ofatumumab.
22) Allergy to clemastine 23) Allergy to paracetamol 24) Glaucoma (contraindication for clemastine)
25) Problems with urination due to prostatic hyperplasia (contraindication for clemastine)
26) Patients on inhaled steroids and long acting beta2-agonists if not stable dose within 4 weeks prior to screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in inflammation measured as number of inflammatory cells in bronchial biopsies including, but not limited to HE-stain, CD3+, CD19+, CD20+, CD68+, elastase, EG2 (eosinophils) and AA1 (mast cells). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.7.1.3.1 | Other trial type description |
First administration in COPD patients |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
The placebo patients will continue in an open part with active treatment as in the double-blind |
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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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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End of trial is when last patient in the open label period have had visit 12 ( follow-up visit) which is 21 weeks after last treatment. (see flow chart i section 1.7 in the protocol).
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |