A clinical trial to evaluate the efficacy and safety of PT027 compared to PT007 in asthma patients 4 years of age or older (MANDALA).
- Conditions
- Moderate to severe asthmaMedDRA version: 20.0Level: LLTClassification code 10015575Term: Exacerbation of asthmaSystem Organ Class: 100000004855MedDRA version: 20.0Level: LLTClassification code 10003561Term: Asthma, unspecifiedSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-003673-10-ES
- Lead Sponsor
- Bond Avillion 2 Development LP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 3100
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;
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 one 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 adolescents, and =60 to <100% predicted normal value for subjects aged 4 to 11 years after withholding the medications specified in Table 4. One re-test is allowed within the screening period in advance of Visit 2;
6 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. One re-test for reversibility testing is allowed within the screening period in advance of Visit 2;
7 Demonstrate acceptable spirometry performance;
8 A documented history of at least 1 severe asthma exacerbation within 12 months before Visit 1;
9 Asthma Control Questionnaire-7 (ACQ-7) score =1.5 assessed at Visit 1
10 ACQ-5 score =1.5 assessed at Visit 2;
11 Use of Sponsor provided Ventolin prn medication due to asthma symptoms on at least 3 days during the last week of the run-in period before Visit 2;
12 Demonstrate acceptable MDI administration technique as assessed by the investigator;
13 Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator;
14 Body mass index <40 kg/m2;
15 Willing to remain at the study site as required per protocol and complete all visit assessments;
16 Negative pregnancy test (serum at Visit 1) for female subjects of childbearing potential;
17 Women of childbearing potential and sexually active in heterosexual relationships must agree to 1 of the following options to prevent pregnancy:
(a) Practice 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 (e.g., oral contraceptive, contraceptive implant, or injectable hormonal contraceptive);
ii. Double-barrier birth control (e.g., condom plus intrauterine device, diaphragm plus spermicide, condom plus spermicide);
iii. Maintenance of a monogamous sexual relationship with a male partner who has been surgically sterilized by vasectomy;
18 Male subjects who are sexually active in heterosexual relationships must be surgically sterile or agree to use a double-barrier method of contraception (condom 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.
Are the trial subjects under 18? yes
Number of subjects for this age
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 (e.g., omalizumab, mepolizumab, reslizumab, benralizumab) 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 (e.g., congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia, coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine (e.g., uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison’s disease, Cushing’s syndrome), or gastrointestinal (e.g., 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 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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method