A clinical trial to evaluate the efficacy and safety of PT027 compared to PT007 in asthma patients 4 years of age or older (MANDALA).

Phase 1

• Conditions: Moderate to severe asthma; MedDRA version: 21.1Level: LLTClassification code 10015575Term: Exacerbation of asthmaSystem Organ Class: 100000004855; MedDRA version: 21.0Level: LLTClassification code 10003561Term: Asthma, unspecifiedSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2018-003673-10-DE
• Lead Sponsor: Bond Avillion 2 Development LP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-27
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 3100

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 re

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified