A multicentre, double-blind, placebo-controlled randomized trial of the efficacy, safety and tolerability of 12 months of once daily treatment with 5 mg of RO3300074 in patients with symptomatic emphysema secondary to alpha-1-antitrypsin deficiency

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-001688-23-DK
• Date of registration: 30/05/2006
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A multicentre, double-blind, placebo-controlled randomized trial of the efficacy, safety and tolerability of 12 months of once daily treatment with 5 mg of RO3300074 in patients with symptomatic emphysema secondary to alpha-1-antitrypsin deficiency
• Scientific title: A multicentre, double-blind, placebo-controlled randomized trial of the efficacy, safety and tolerability of 12 months of once daily treatment with 5 mg of RO3300074 in patients with symptomatic emphysema secondary to alpha-1-antitrypsin deficiency
• Date of first enrolment: 05/07/2006
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001688-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Denmark, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men >= 30 years of age with AATD of the Pi Z or Pi Null phenotype.
2. Women >= 30 years of age with AATD of the Pi Z or Pi Null phenotype beyond child-bearing potential defined as women who are more than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy.
3. Non-smokers with clinical diagnosis of emphysema with confirmation by radiographic imaging (ex-smokers must have stopped smoking for ? 6 months prior to enrollment).
4. TLco (KCO ) < 60% of the predicted normal value.
5. Base-line FEV1 <= 70 % of the predicted normal value for gender, age, and height and measured before administration of a bronchodilator.

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. AATD patients on concomitant Prolastin replacement therapy.
2. Psychiatric disorders requiring medication or hospitalization, or with suicide attempt within the last 7 years.
3. More than 3 exacerbations of pulmonary symptoms, requiring treatment with oral steroids, or antibiotics, within 12 months prior to this study.
4. Total score of the depression scale CES-D of >= 60
5. Patients with giant bullous disease.
6. Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient’s ability to perform the study tests.
7. Hypertriglyceridemia >= 300mg/dl with therapy
8. Concomitant medications which are inhibitors or inducers of CYP 450 3A4 activity


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

Health Condition(s) or Problem(s) studied

symptomatic emphysema secondary to alpha-1-antitrypsin deficiency

Intervention(s)

Product Name: Not applicable
Product Code: RO3300074
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: None assigned
Other descriptive name: Retinoic Acid Receptor gamma Agonist
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy measure is the change from baseline in 12 months of the 15th percentile of the lung density adjusted for the lung volume as obtained by computer tomography (spiral CT scanner) using lung density histograms. The CT densitometry measurements will be performed at baseline, after 28 and after 52 weeks of treatment.

Main Objective: This is a phase II proof of concept study to investigate efficacy, safety and tolerability of 5.0 mg of RO3300074 when administered once daily for 12 months (52 weeks) compared with placebo. The primary efficacy measure is the change from baseline in 12 months of the 15th percentile of the lung density adjusted for the lung volume as obtained by computer tomography (spiral CT scanner) using lung density histograms

Secondary Objective: Secondary objectives include assessment of lung function including spirometry, TLco, lung volumes, arterial blood gases, exercise, quality of life, assessments of dyspnea, and plasma biomarkers.

Secondary ID(s)

2004-001688-23-ES

NA17598