Clinical Trial Page

Summary
EudraCT Number:2022-001476-33
Sponsor's Protocol Code Number:D5985C00003
National Competent Authority:Bulgarian Drug Agency
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-10-28
Trial results
A. Protocol Information
A.1Member State ConcernedBulgarian Drug Agency
A.2EudraCT number2022-001476-33
A.3Full title of the trial
A Randomized, Double-Blind, 12-Week (with an Extension to 52 weeks in a subset of Participants), Multi-Center Study to Assess the Safety of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO Compared to BGF delivered by MDI HFA in Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Study to Assess the Safety of Budesonide/Glycopyrronium/Formoterol Fumarate with the Hydrofluoroolefin Propellant in Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease
A.4.1Sponsor's protocol code numberD5985C00003
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAstraZeneca AB
B.1.3.4CountrySweden
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAstraZeneca AB
B.4.2CountrySweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAstraZeneca AB
B.5.2Functional name of contact pointClinical Study Information Center
B.5.3 Address:
B.5.3.1Street Address1800 Concorde Pike
B.5.3.2Town/ cityWilmington
B.5.3.3Post codeDE 19803
B.5.3.4CountryUnited States
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Trixeo Aerosphere
D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.2Product code BGF MDI HFA
D.3.4Pharmaceutical form Pressurised inhalation, suspension
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPInhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNBudesonide
D.3.9.1CAS number 51333-22-3
D.3.9.3Other descriptive nameBudesonide
D.3.9.4EV Substance CodeSUB05955MIG
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number160
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFormoterol fumarate
D.3.9.1CAS number 183814-30-4
D.3.9.3Other descriptive nameFORMOTEROL FUMARATE DIHYDRATE
D.3.9.4EV Substance CodeSUB25660
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number4,8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGlycopyrronium
D.3.9.1CAS number 51186-83-5
D.3.9.3Other descriptive nameGlycopyrronium Bromide
D.3.9.4EV Substance CodeSUB02381MIG
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number7.2
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameBGF MDI HFO (contains HFO1234ze propellant)
D.3.4Pharmaceutical form Pressurised inhalation, suspension
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPInhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNBudesonide
D.3.9.1CAS number 51333-22-3
D.3.9.3Other descriptive nameBudesonide
D.3.9.4EV Substance CodeSUB05955MIG
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number160
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFormoterol fumarate
D.3.9.1CAS number 183814-30-4
D.3.9.3Other descriptive nameFORMOTEROL FUMARATE DIHYDRATE
D.3.9.4EV Substance CodeSUB25660
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number4,8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGlycopyrronium
D.3.9.1CAS number 51186-83-5
D.3.9.3Other descriptive nameGlycopyrronium bromide
D.3.9.4EV Substance CodeSUB02381MIG
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number7.2
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
E.1.1.1Medical condition in easily understood language
Chronic Obstructive Pulmonary Disease
E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10010952
E.1.2Term COPD
E.1.2System Organ Class 100000004855
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
Safety objectives: To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA over 12 to 52 weeks in participants with moderate to very severe COPD
E.2.2Secondary objectives of the trial
Exploratory objectives:
1. To assess the safety and tolerability of BGF MDI HFO compared to BGF MDI HFA over 12 to 52 weeks in participants with moderate to very severe COPD
2. To explore the effect of BGF MDI HFO compared to BGF MDI HFA over 12 to 52 weeks on respiratory health status
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
Age
1.Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF;
Type of Participant and Disease Characteristics
2.Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004) or by locally applicable guidelines;
3.Participants who have been regularly using dual ICS/LABA, LAMA/LABA, or ICS/LAMA/LABA (open or fixed-dose combinations) inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening;
4.Participants who have pre-bronchodilator FEV1 of < 80% predicted normal at Visit 1;
5.Participants who have post-bronchodilator FEV1/FVC ratio of < 0.70 and post bronchodilator FEV1 of ≥ 25% to < 80% predicted normal at Visit 2;
6.Participants who have CAT score ≥ 10 at Visit 1;
7.Participants who are current/former smokers with a history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked per day for 1 year);
8.Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol;
9.Participants must be able to demonstrate acceptable MDI administration and spirometry technique;
10.Participants who are willing to remain at the study center as required per protocol to complete all visit assessments;
Sex
11.Females must either be not of childbearing potential, or using a form of highly effective birth control as defined below:
oWomen not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:
oWomen < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
oWomen ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of all exogenous hormonal treatment.
12.Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. At enrollment, women of childbearing potential who are sexually active with a non-sterilized male partner should be stable on their chosen method of highly effective birth control, as defined below, and willing to remain on the birth control until at least 14 days after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
oAll women of childbearing potential must have a negative serum pregnancy test result at Visit 1
oWomen <50 years of age with amenorrhea for 12 months without an alternative medical cause must have a serum LH and FSH test (within 21-28 days before Visit 3) for study eligibility
Highly effective birth control methods are listed below:
oSexual abstinence defined as complete abstinence from intercourse when it is the preferred and usual lifestyle of the participant (however, periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception)
oContraceptive subdermal implant
oIntrauterine device or intrauterine system
oOral contraceptive (combined or progesterone only)
oInjectable progestogen
oContraceptive vaginal ring
oPercutaneous contraceptive patches
oMale partner sterilization with documentation of azoospermia prior to the female participant’s entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel’s review of participant’s medical records, medical examination and/or semen analysis or medical history interview provided by her or her partner
oBilateral tubal ligation
Informed Consent
13.Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
E.4Principal exclusion criteria
1.Participants who have a documented history of physician-diagnosed asthma in the opinion of the Investigator based on thorough review of medical history and medical records, within 5 years of Visit 1
2.Participants who have COPD due to α1-Antitrypsin Deficiency
3.Participants with historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary.
4.Sleep apnea that, in the opinion of the Investigator, cannot be controlled
5.Other respiratory disorders including known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis, immune deficiency disorders, severe neurological disorders affecting control of the upper airway, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease
6.Participant with moderate or severe COPD exacerbation or respiratory infection ending within 4 weeks prior to Visit 1 or during the Screening period
7.Participant who has had a SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the Screening Period or that required hospitalization at any time prior to Visit 1 or during the Screening Period
8.Pulmonary resection or lung volume reduction surgery during the 26 weeks (6 months) prior to Visit 1 (ie, lobectomy, bronchoscopy lung volume reduction [endobronchial blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological sealants, and airway implants])
9.Long-term oxygen therapy
10.Imminent life-threatening COPD (eg, need for mechanical ventilation)
11.Participant who has significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator
12.Participant with narrow angle glaucoma not adequately treated and/or change in vision that may be relevant, in the opinion of the Investigator
13.Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant
Note: Participants with trans-urethral resection of prostate or full resection of the prostate within 26 weeks (6 months) prior to Visit 1 are excluded from the study
14.Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1
15.Known history of drug or alcohol abuse within 52 weeks (12 months) of Visit 1
16.Unable to withhold short-acting bronchodilators for 6 hours prior to lung function testing at each applicable study visit
17.Participant is unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods
18.Using any herbal products either by inhalation or nebulizer within 2 weeks of Visit 1 and does not agree to stop for the duration of the study
19.Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI
20.Participation in another clinical study with an intervention administered in the last 30 days or 5 half-lives, whichever is longer
21.Previous randomization in any study using BGF MDI HFO
22.Participants with calculated eGFR ≤ 30 mL/minute/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
23.Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study Note: Participants with ECG QTcF interval (corrected for heart rate using Fridericia’s formula [QTcF]) > 480 msec will be excluded. Participants with high degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker will also be excluded.
24.Planned hospitalization during the study
25.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
26.Study Investigators, sub-Investigators, coordinators, and their employee or immediate family members
27.Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements
28.For women only – currently pregnant (confirmed with positive pregnancy test), breast feeding, or planned pregnancy during the study or women of childbearing potential not using acceptable contraception measures
E.5 End points
E.5.1Primary end point(s)
1. AEs (including SAEs, DAEs, AEOSIs, non-serious AEs)
2. Digital 12-lead Holter electrocardiogram (ECG)
3. 12-lead ECG
4. Clinical laboratory testing
5. Vital signs
E.5.1.1Timepoint(s) of evaluation of this end point
1. Over 16 or 56 Weeks (if attending 56 weeks study)
2. Week 0 and week 12
3. Week 4, 8 and 52 (if attending 56 weeks study)
4. Week 0, 12 and 52 (if attending 56 weeks study)
5. Over 14 or 54 Weeks (if attending 56 weeks study)
E.5.2Secondary end point(s)
1. Change from pre-dose value in FEV1 at 5, 15, 30, and 60 min post dose
2. Change from baseline COPD Assessment Test (CAT) at 12 and 52 weeks
E.5.2.1Timepoint(s) of evaluation of this end point
1. Over 12 or 52 Weeks (if attending 56 weeks study)
2. Week 12 and 52 (if attending 56 weeks study)
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy No
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.3.1Comparator description
BGF MDI HFA
E.8.2.4Number of treatment arms in the trial2
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.8.4.1Number of sites anticipated in Member State concerned6
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA50
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Argentina
Bulgaria
Canada
Germany
Mexico
Poland
Turkey
United Kingdom
United States
E.8.7Trial 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
The study will end when the last remaining participant completes his/her Week 52/Visit 9 (Week 12/Visit 6 for participants contributing only to the 12 weeks safety study) and subsequent 2-week follow-up telephone contact. If study intervention is discontinued prior to the Week 52/Visit 9(Week 12/Visit 6 for participants contributing only to the 12 weeks safety study), then study will end at the completion of the Withdrawal Visit and subsequent 2-week follow-up telephone contact.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months9
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months9
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 361
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 181
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state60
F.4.2 For a multinational trial
F.4.2.1In the EEA 217
F.4.2.2In the whole clinical trial 542
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Participants who complete Week 52/Visit 9/Withdrawal Visit (or Week 12/Visit 6/Withdrawal Visit for those not entering the Extension study) should be given locally available standard-of-care treatment at the discretion of the Investigator.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-11-02
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-09-30
P. End of Trial
P.End of Trial StatusOngoing