A double-blind, randomized, placebo-controlled, multi-center, Clinical Trial of ofatumumab, a fully human monoclonal anti-CD20 antibody in patients with moderate to severe stage Chronic Obstructive Pulmonary Disease

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-003184-31-GB
• Date of registration: 15/05/2007
• Prospective Registration: Yes
• Primary sponsor: Genmab A/S
• Public title: A double-blind, randomized, placebo-controlled, multi-center, Clinical Trial of ofatumumab, a fully human monoclonal anti-CD20 antibody in patients with moderate to severe stage Chronic Obstructive Pulmonary Disease
• Scientific title: A double-blind, randomized, placebo-controlled, multi-center, Clinical Trial of ofatumumab, a fully human monoclonal anti-CD20 antibody in patients with moderate to severe stage Chronic Obstructive Pulmonary Disease
• Date of first enrolment: 31/05/2007
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003184-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: The placebo patients will continue in an open part with active treatment as in the double-blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, United Kingdom

Key inclusion & exclusion criteria

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 6 months and a maximum of 14 years having smoked = 15 cigarettes per day = 20 years (15 pack-years)
5) GOLD lower part of stage 2 and stage 3 (FEV1/FVC < 70%, 30% = FEV1 < 60% 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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) Positive serology for hepatitis B, defined as a positive test for HBsAg and/or a combination of a positive test for anti-HBs and anti HBc
15)Screening laboratory values:
- WBC < 3.0x10E9/L
- Neutrophils < 1.5 x10E9/L
- Platelets < 75 x10E9/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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe stage of Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 8.1 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Name: ofatumumab
Product Code: HuMax-CD20
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ofatumumab
CAS Number: 679818-59-8
Current Sponsor code: HuMax-CD20
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To evaluate efficacy of ofatumumab in decreasing inflammation in COPD assessed by bronchial biopsies.

Secondary Objective: To evaluate the safety of ofatumumab in patients with COPD and to describe changes in inflammatory mediators in serum and BAL.
To describe objective and subjective changes following treatment with ofatumumab.

Primary end point(s): Change in inflammation measured as number of inflammatory cells in bronchial biopsies including, but not limited to, CD3+, CD4+, CD8+, CD19+, CD20+, CD68+, elastase, EG2 (eosinophils) and AA1 (mast cells)

Secondary ID(s)

Hx-CD20-408