A single-centre, randomised, double-blind, placebo-controlled, cross-over study to assess the efficacy of a 5-day, once daily 10-mg PBF-680 oral administration course to attenuate allergen bronchoprovocation-induced late asthmatic responses (LAR) in asthmatic patients controlled on low-to-medium dose inhaled corticosteroid maintenance monotherapy and inhaled short-acting beta-2 agonist as rescue bronchodilator.

• Register: EUCTR
• Last refreshed on: 26 April 2021
• Main ID: EUCTR2015-001957-34-ES
• Date of registration: 05/10/2015
• Prospective Registration: No
• Primary sponsor: Palobiofarma S.L.
• Public title: A single-centre, randomised, double-blind, placebo-controlled, cross-over study to assess the efficacy of a 5-day, once daily 10-mg PBF-680 oral administration course to attenuate allergen bronchoprovocation-induced late asthmatic responses (LAR) in asthmatic patients controlled on low-to-medium dose inhaled corticosteroid maintenance monotherapy and inhaled short-acting beta-2 agonist as rescue bronchodilator.
• Scientific title: A single-centre, randomised, double-blind, placebo-controlled, cross-over study to assess the efficacy of a 5-day, once daily 10-mg PBF-680 oral administration course to attenuate allergen bronchoprovocation-induced late asthmatic responses (LAR) in asthmatic patients controlled on low-to-medium dose inhaled corticosteroid maintenance monotherapy and inhaled short-acting beta-2 agonist as rescue bronchodilator - Single-centre, randomised, double-blind, placebo-controlled, cross-over efficacy study of PBF-680
• Date of first enrolment: 14/09/2015
• Target sample size: 16
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001957-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Clinical Trials Information
• Affiliation: Palobiofarma S.L.

• Name: Clinical Trials Information
• Affiliation: Palobiofarma S.L.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for inclusion into the screening period and to perform the visits V1 and V2 test-based selection procedures must fulfill all of the following criteria:
1. Male and female adults aged >=18, who have signed the informed consent form prior to initiation of any study procedures.
2. Subjects who have controlled asthma, diagnosed and determined as such as per the GINA guidelines, with low-to-medium dose ICS as maintenance monotherapy and inhaled, short-acting ?2-agonist bronchodilator as rescue medication, for a minimum 4-week period before screening visit V1. Controlled asthma under the stated therapy can be the current, stable condition presented at visits V0 and V1 or can be achieved through GINA guideline-based clinical practice through one or more discretionary V0b visits.
3. Subjects must have a body mass index between 18 and 35 kg/m².
4. Subjects must be able to perform acceptable spirometry in accordance with ATS/ERS criteria for acceptability and repeatability.
5. Subjects must have a baseline FEV1>=70% of predicted normal, and greater than 1 L in absolute value, on visit V1.
6. Subjects meeting criterion 1 must have a positive skin prick allergy test to at least one tested aeroallergen, defined as causing a >=2 mm wheal, on visit V1.
7. Subjects meeting criteria 1 and 2 must show airway hyperresponsiveness to AMP, defined as per an AMP PC20<=200 mg/mL, on visit V1.
8. On visit V2, subjects meeting criteria 1, 2 and 3 must develop a LAR following bronchoprovocation with the chosen allergen, defined as a FEV1 drop >=15% from post-diluent FEV1, in at least three time points between 4 and 10 hours post-bronchoprovocation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects eligible for inclusion into the screening period and randomization must not meet any of the following criteria:
1. Current smokers, smokers within six months prior to Visit V1, or subjects with a smoking history greater than 10 packs-years.
2. Asthmatics classed as "intermittent asthma" managed in GINA-1 therapeutic step or asthmatics that need any maintenance controller medication beyond low-to-medium ICS.
3. Patients under any immunosuppressive medication whether asthma-related or indicated for any concomitant morbidities.
4. Subjects with a history of life-threatening asthma attacks (i.e. requiring ICU admission, orotracheal intubation).
5. Subjects with a history of a respiratory tract infection or an asthma exacerbation requiring the use of antibiotics and/or systemic corticosteroids within 4 weeks prior to visit V1, or who develop a respiratory tract infection or asthma exacerbation during the screening period. In the latter case, the subjects can be re-screened 4 weeks after the last dose of systemic corticosteroid or antibiotic.
6. Subjects that received bronchial thermoplasty treatment.
7. Subjects with a concomitant pulmonary or thoracic disease other than asthma that may compromise safety or interfere with efficacy outcomes as per site investigator assessment. This includes, but is not limited to, COPD attributable to tobacco or alpha-1-antitrypsin deficiency, cystic fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, active pulmonary tuberculosis, or any prior condition that led to pulmonary resection surgery or lung transplantation. Non-cystic fibrosis bronchiectasis without clinically significant morbidity, moderate alpha-1-antitrypsin deficiency without evidence of emphysema or related COPD, or past pulmonary tuberculosis that received proper medical treatment, are acceptable provided that the condition is not expected to interfere with pulmonary function testing as per site investigator assessment.
8. Subjects with any skin condition such as demographism that may prevent correct interpretation of skin prick allergy tests.
9. Subjects with symptoms of angina pectoris or with a history of confirmed coronary disease or cardiomyopathy.
10. Subjects with A-V block in any degree, sinus bradycardia, tachyarrhythmia, unstable atrial fibrillation, long QT syndrome, QTc(F) interval greater than 450 ms at screening EKG on visit V1, or any other EKG abnormality deemed clinically significant by the investigator.
11. Subjects who have a clinically significant laboratory abnormality at screening blood analysis on visit V2+24h.
12. Subjects with current uncontrolled arterial hypertension.
13. Women of child-bearing potential, unless they are surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), are at least 2 years postmenopausal, practice abstinence, or agree to employ effective contraception from Visit 1 through visit VFU. Acceptable contraception procedures are oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, or use of a condom with spermicide by the sexual partner.
14. Women supplying lactation.
15. Receipt of any investigational drug or biological therapy within 3 months before randomization in this study, or within 5 half-lives of the investigational agent, whichever is longer. Subjects ever treated with omalizumab or other biological therapies for asthma are not eligible

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Treatment for asthma.
MedDRA version: 18.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: PBF-680
Pharmaceutical Form: Capsule
INN or Proposed INN: PBF-680
Current Sponsor code: PBF-680
Other descriptive name: PBF680
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Measured from 4-10 hour post-allergen bronchoprovocation.

Main Objective: To demonstrate the effect of a 5-day oral administration course of 10 mg PBF-680, as compared to placebo in a 2-way cross-over fashion, in terms of LAR attenuation as determined by the 4-to-10 hour FEV1 AUC post-allergen bronchoprovocation.

Secondary Objective: To demonstrate the effect of a 5-day oral administration course of 10 mg PBF-680, as compared to placebo in a 2-way cross-over fashion, on:
- The EAR, measured as the maximum FEV1 fall from the postdiluent value within 1 hour post-allergen bronchoprovocation.
- The FeNO at 24-hour post-allergen bronchoprovocation (nitric oxide parts-per-billion fraction in exhaled air).
- Airway hyperresponsiveness to AMP at 24-hour post-allergen bronchoprovocation in terms of PC20 increment in response to AMP airway challenge.
- Total leukocytes per mL and leukocyte differential counts in induced sputum at 24-hour post-allergen bronchoprovocation, as percentage and absolute numbers per mL of monocyte/macrophages, eosinophils, neutrophils and lymphocytes.
- To assess safety and tolerability in asthmatics.
- To generate extended data on PBF-680 pharmacokinetics.

Primary end point(s): The primary efficacy variable will be the 4-10 hour post-allergen bronchoprovocation FEV1-fall AUC.

Secondary Outcome(s)

Secondary end point(s): Secondary outcomes will include early asthmatic response (EAR) assessment as per FEV1 drop within 1 hour post-allergen bronchoprovocation, and the determination of FeNO, AMP challenge PC20 and leukocyte differential counts in induced sputum at 24 hours post-allergen bronchoprovocation. Safety assessment will include monitoring of adverse events, physical examination, vital signs, ECGs, spirometry, serum and urine pregnancy tests, and laboratory determinations. Blood sampling at a time-point series will provide pharmacokinetics data.

Timepoint(s) of evaluation of this end point: Early asthmatic response (EAR) assessed within 1 hour post-allergen bronchoprovocation. FeNO, AMP challenge PC20 and leukocyte differential counts in induced sputum will be measured at 24 hours post-allergen bronchoprovocation.

Secondary ID(s)

IIBSP-PBF-2015-34

Source(s) of Monetary Support

Palobiofarma S.L.

Ethics review

Status: Approved
Approval date: 27/05/2015
Contact: