| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe asthma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015575 |
| E.1.2 | Term | Exacerbation of asthma |
| E.1.2 | System Organ Class | 100000004855 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003561 |
| E.1.2 | Term | Asthma, unspecified |
| E.1.2 | System Organ Class | 100000004855 |
|
| 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 the efficacy of budesonide/albuterol metered-dose inhaler 80/180 μg and 160/180 μg administered prn in response to symptoms compared to albuterol metered-dose inhaler 180 μg. |
|
| E.2.2 | Secondary objectives of the trial |
| To characterize the effect of budesonide/albuterol metered-dose inhaler 80/180 μg and 160/180 μg administered prn in response to symptoms compared to albuterol metered-dose inhaler 180 μg. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study, subjects must fulfill the following criteria within the screening period:
1 Able and willing to provide written informed consent or sign age-appropriate forms, subjects below legal age of consent must have parent(s) or guardian sign the ICF before participation;
2 Female or male aged ≥4 years at the time of informed consent in all countries with the exception of the following: in Serbia only subjects ≥12 years old will be enrolled; in Germany, Slovakia, and Ukraine, only subjects ≥18 years old will be enrolled;
3 Diagnosis of asthma as defined by GINA criteria at least 1 year before Visit 1;
4 Receiving 1 of the following scheduled asthma maintenance therapies for 3 months with stable dosing for at least the last 4 weeks before Visit 1;
(a) Medium-to-high-dose ICS;
(b) Medium-to-high-dose ICS and 1 additional maintenance therapy from the following: LTRA, LAMA, or theophylline;
(c) Low-to-high-dose ICS in combination with LABA with or without 1 additional maintenance therapy from the following: LTRA, LAMA, or theophylline;
5 Prebronchodilator forced expiratory volume in 1 second (FEV1) of ≥40 to <90% predicted normal value for adults, and ≥60 predicted normal value for subjects aged 4 to 17 years after withholding the medications specified in Table 4. If FEV1 values are not within the permitted range at Visit 1, 1 re-test must be performed at Visit 1a before advancing to Visit 2 or confirming screen failure; Note: Subjects 4 to 17 years of age who previously failed inclusion criterion 5 due to the previous upper FEV1 limit will be permitted to re-screen once and will be required to meet all other eligibility criteria upon re-screening.
6 Subjects aged ≥12 years of age must demonstrate reversibility at Visit 1, with an increase in FEV1 ≥12% (and ≥200 mL for subjects aged ≥18 years) relative to baseline after administration of Sponsor provided Ventolin via central spirometry. If reversibility is not demonstrated at Visit 1, 1 re-test for reversibility testing must be done at Visit 1a before advancing to Visit 2 or confirming screen failure. Subjects aged 4 to 11 years of age will perform the reversibility test, but do not require demonstration of reversibility during Visit 1 and may enroll provided documented historical reversibility within 1 year is available. Subjects aged 4 to 11 years who previously failed inclusion criterion 6 will be permitted to rescreen. Each subject may re-screen only once ;
7Demonstrate acceptable spirometry performance; Subjects 4 to 11 years will be eligibile if they provide 2 acceptable/repeatable measurements.
8A documented history of at least 1 severe asthma exacerbation within 12 months before Visit 1;
9Asthma Control Questionnaire-7 (ACQ-7) score ≥1.5 assessed at Visit 1
10ACQ-5 score ≥1.5 assessed at Visit 2;
11Use of Sponsor provided Ventolin prn medication because of asthma symptoms on at least 3 days during the last week of the run-in period before Visit 2;
12Demonstrate acceptable MDI administration technique as assessed by the investigator, use of spaciers prohibited;
13Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator;
14Body mass index <40 kg/m2;
15Willing to remain at the study site as required per protocol and complete all visit assessments;
16Negative pregnancy test (serum at Visit 1) for female subjects of childbearing potential;
17Women of childbearing potential and sexually active in heterosexual relationships must agree to 1 of the following options to prevent pregnancy:
(a)Practice complete abstinence;
(b)If a female of childbearing potential agrees to prevent pregnancy by using 1 of the following methods of birth control from the date the ICF is signed until 2 weeks after the final dose of IP is taken:
i.Hormonal contraception (eg., oral contraceptive, contraceptive implant, or injectable hormonal contraceptive);
ii.Double-barrier birth control (eg. a combination of male condom with either cap, diaphragms, or sponge with spermicide, intrauterine device [IUD] and intrauterine hormone-releasing system [IUS])
iii.Maintenance of a monogamous sexual relationship with a male partner who has been surgically sterilized by vasectomy provided that the male partner is the sole sexual partner of the female (of child bearing potential) participant and that the vasectomized partner has received medical assessment of the surgical success (ie, documented history of medical confirmation of success of vasectomy);
18Male subjects who are sexually active in heterosexual relationships must be surgically sterile or agree to use a double-barrier method of contraception (a combination of male condom with either cap, diaphragms, or sponge with spermicide) from the first dose of randomized IP until 2 weeks after their last dose. Male subjects must not donate sperm during their study participation period.
Please refer to protocol for complete inclusion critieria. |
|
| E.4 | Principal exclusion criteria |
Subjects must not enter the study if any of the following exclusion criteria are fulfilled within the screening period:
1 Chronic obstructive pulmonary disease or other significant lung disease;
2 Oral/SCS use (any dose and any indication) within 6 weeks before Visit 1;
3 Chronic use of oral corticosteroids (OCS, ≥3 weeks use in 3 months prior to Visit 1);
4 Having received any marketed (eg., omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) or investigational biologic within 3 months or 5 half-lives before Visit 1, whichever is longer, or any other prohibited medication;
5 Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and marijuana);
6 Life-threatening asthma defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within 5 years of Visit 1;
7 Completed treatment for lower respiratory infection or asthma exacerbation within 6 weeks of Visit 1;
8 Upper respiratory infection involving antibiotic treatment not resolved within 7 days before Visit 1;
9 Clinically significant laboratory abnormalities, in the opinion of the investigator;
10 Having any of the following results at Visit 1:
(a) an abnormal electrocardiogram (ECG) that is, in the investigator’s opinion, clinically significant;
(b) a QTCF interval >480 ms (subjects aged ≥12 years)/ ≥460 ms (subjects aged 4 to 11 years, based on the Fridericia correction where QTCF=QT/RR0.33);
11 Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular (eg., congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia, coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine (eg., uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison’s disease, Cushing’s syndrome), or gastrointestinal (eg., poorly controlled peptic ulcer, gastroesophageal reflux disease) disorders. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation, or that could affect the efficacy or safety analysis if the disease/condition exacerbated during the study;
12 Cancer not in complete remission for at least 5 years before Visit 1;
13 Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1;
14 History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity;
15 Significant abuse of alcohol or drugs, in the opinion of the investigator;
16 Having a known or suspected hypersensitivity to albuterol/salbutamol, or budesonide and/or their excipients;
17 Having a scheduled/planned hospitalization during the study;
18 Inability to abstain from protocol-defined prohibited medications during the study;
19 Using any herbal products by inhalation or nebulizer within 2 weeks of Visit 1 and not agreeing to stop during the study duration;
20 Having received a live attenuated vaccination within 7 days of Visit 1;
21 Currently pregnant and breastfeeding;
22 Study investigators, subinvestigators, coordinators, and their employees or immediate family members, or employees of the Sponsor;
23 Treatment with any investigational treatment or device in another clinical study within the last 30 days (or 5 half-lives, whichever is longer) of Visit 1;
24 Currently participating in any interventional study;
25 Having previously been randomized in this study or any other PT007 or PT027 clinical study.
26 Subjects who experience >1 asthma exacerbatin during the screening period |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to first severe asthma exacerbation. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Time to first severe asthma exacerbation will be calculated as the time from randomization until the start date of the first severe asthma exacerbation. |
|
| E.5.2 | Secondary end point(s) |
• Severe exacerbation rate (annualized)
• Total systemic corticosteroid exposure over the treatment period
• Asthma Control Questionnaire -5 (ACQ-5) change from baseline and responder analysis at Week 24
• Asthma Quality of Life Questionnaire for 12 years and older/ (AQLQ+12) Pediatric Asthma Quality of Life Questionnaire (PAQLQ) change from baseline and responder analysis at Week 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the study and as defined within the end points. |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 54 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 111 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Chile |
| Serbia |
| South Africa |
| Argentina |
| Austria |
| Canada |
| Czechia |
| Germany |
| Italy |
| Slovakia |
| Spain |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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