A 52-week, randomized, double-blind, double-dummy, placebo- and active- controlled (Roflumilast, Daliresp® 500µg), parallel group, study to evaluate the efficacy and safety of two doses of CHF6001 DPI add-on to maintenance triple therapy in subjects with Chronic Obstructive Pulmonary Disease (COPD) and chronic bronchitis.
- Conditions
- No synonym10006436
- Registration Number
- NL-OMON56320
- Lead Sponsor
- Chiesi Farmaceutici
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 220
Subjects must meet all the following inclusion criteria to be eligible for
enrolment into the study:
1. Males and females aged >= 40 years with written informed consent obtained
prior to any study-related procedure.
2. Females are eligible to enter the study if she is of
a. non- childbearing potential i.e. physiologically incapable of becoming
pregnant (e.g. postmenopausal women defined as being amenorrhoeic for >=12
consecutive months without an alternative medical cause*) or women permanently
sterilized (e.g. bilateral oophorectomy, hysterectomy or bilateral
salpingectomy).
or
b. childbearing potential, they must have a negative pregnancy test at
screening and must agree to use one or more of the following acceptable
contraceptive measures:
i. Placement of an intrauterine device (IUD) or intrauterine hormone-releasing
system (IUS).
ii. Combined (oestrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, transdermal).
iii. Progesterone-only hormonal contraception associated with inhibition of
ovulation (oral, injectable, implantable).
iv. Bilateral tubal occlusion.
v. Vasectomized partner.
vi. Double barrier method: condom and an occlusive cap (diaphragm or cervical/
vault caps) with a vaginal spermicidal agent.
Reliable contraception should be maintained throughout the study. Abstinence is
acceptable where it is in line with the subject*s
preferred and usual lifestyle. Pregnancy tests will be performed at screening
(urine and serum tests) and at randomization (urine test
only) in all women of childbearing potential.
3. Subjects with an established diagnosis of COPD (according to GOLD 2020) at
least 12 months before the screening visit, with
chronic bronchitis (defined as productive cough for at least 3 months in each
of the prior two consecutive years) and/or with chronic productive cough >=12
months prior to screening.
4. Current smokers or ex-smokers who quit smoking at least 6 months prior to
screening visit, with a smoking history of at least 10 pack years [pack-years =
(number of cigarettes per day x number of years)/20] (If the subjects undergo
smoking cessation therapy, it must be completed 3 months prior to the screening
visit). E-cigarettes and pipe smokers are allowed. E-cigarettes cannot be used
to calculate pack-year history.
5. A post-bronchodilator FEV1 <50% of the patient predicted normal value and a
post-bronchodilator FEV1/FVC ratio < 0.7 after 400µg
(4 puffs x 100µg) of salbutamol pMDI. If this criterion is not met at
screening, the test can be repeated once before randomization.
6. A documented history (e.g. medical record verification) of at least one
moderate or severe COPD exacerbation in the previous year.
Documented visits to an emergency department due to COPD exacerbation
associated with prescription of systemic steroids/antibiotics, are considered
acceptable to fulfil this criterion. A stay in emergency room >=24h will be
considered a severe event.
7. Symptomatic subject at screening defined as having a CAT score >=10.
8. Subjects prescribed with maintenance triple therapy (free or fixed
combination of ICS, LABA, LAMA) according to GOLD 2020 recommendations, for at
least 12 months prior to screening and receiving regular maintenance triple
therapy for at
EXCLUSION CRITERIA
The presence of any of the following will exclude a patient from study
enrolment:
1. Subjects with a diagnosis of current asthma. Those with prior history of
asthma in childhood are eligible.
2. Subjects with a moderate or severe COPD exacerbation i.e. resulting in the
use of systemic corticosteroids (oral/IV/IM corticosteroids) and/or antibiotics
or need for hospitalisation or a lower respiratory tract infection 4 weeks
prior to study entry and during run-in period.
3. Pregnant and Lactating women.
4. Subjects requiring long term (at least 15 hours daily) oxygen therapy for
chronic hypoxemia.
5. Subjects with known a-1 antitrypsin deficiency as the underlying cause of
COPD.
6. Subjects with primary diagnosis of emphysema not related to COPD
7. Subjects with clinically significant respiratory disorders other than COPD.
This can include but is not limited to active tuberculosis, significant
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and
interstitial lung disease.
8. Subjects with lung volume reduction surgery.
9. Subjects having lung cancer or a history of lung cancer or lung cancer with
full recovery less than 1 year after completing cancer therapy.
10. Subjects with active cancer or a history of cancer (other than the lung)
with full recovery less than 1 year after completing cancer therapy or any
untreated localized carcinoma.
11. Subjects with a history of allergy or hypersensitivity to anticholinergics,
β2-agonists, corticosteroids, PDE-4 inhibitors or any of the excipients
contained in any of the formulations used in the trial or a medical condition
such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck
obstruction that in the investigator*s opinion would contra-indicate study
participation.
12. Subjects under Roflumilast treatment within 6 months before study entry.
13. Subjects with a diagnosis of depression, generalised anxiety disorder,
suicidal ideation or behaviour that might, according to the investigator
judgement, place the patient at undue risk.
14. Subjects who have clinically significant cardiovascular condition such as,
but not limited to unstable ischemic heart disease, NYHA Class III/IV left
ventricular failure, acute ischemic heart disease within one year prior to
study entry, known history of atrial fibrillation or of sustained and
non-sustained cardiac arrhythmias diagnosed within the last 6 months prior to
study entry, not controlled with a rate and/or rhythm control strategy or with
recurrent episodes in the last 6 months.
15. An abnormal and clinically significant 12-lead ECG finding in relation to
the subject*s medical history that results in active medical problem which may
impact the safety of the patient according to investigator*s judgement. An
abnormal and clinically significant finding that would exclude the subject from
study participation is defined as an ECG tracing that is interpreted as, but
not limited to, any of the following:
• atrial fibrillation with rapid ventricular rate >120 bpm
• sustained or non-sustained ventricular tachycardia
• second degree AV block Mobitz type II and third-degree AV block (unless
pacemaker or defibrillator had been inserted)
• QTcF >=480 msec (at screening visit). Criterion not applicable for subjects
with pacem
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the efficacy of two doses of CHF6001 add-on to maintenance triple<br /><br>therapy (free or fixed combination of ICS, LABA, LAMA) to reduce the rate of<br /><br>moderate and severe exacerbations after 52 weeks of treatment in comparison<br /><br>with maintenance triple therapy (i.e. placebo arm). </p><br>
- Secondary Outcome Measures
Name Time Method <p>Key Secondary: To evaluate the efficacy of the two doses of CHF6001 add-on to<br /><br>maintenance triple therapy on health-related quality of life after 52 weeks of<br /><br>treatment (change in SGRQ total score).<br /><br><br /><br>Secondary:<br /><br>To evaluate<br /><br>- the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy<br /><br>on lung function, health-related quality of life, severe exacerbations in the<br /><br>pooled analysis of CLI-06001AA1-04 and CLI-06001AA1-05 studies and other<br /><br>clinical outcome measures in comparison with maintenance triple therapy<br /><br>- the safety and tolerability of the two doses of CHF6001<br /><br>- the efficacy, safety and tolerability of the two doses of CHF6001 in<br /><br>comparison with Roflumilast. </p><br>