A Dose-Ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with a Common Cold Infection.

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2014-001785-95-CZ
• Date of registration: 31/12/2014
• Prospective Registration: Yes
• Primary sponsor: Biota Pharmaceuticals, Inc.
• Public title: A Dose-Ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with a Common Cold Infection.
• Scientific title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Dose-ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with Symptomatic Human Rhinovirus Infection. - Phase 2 Asthma
• Date of first enrolment: 16/03/2015
• Target sample size: 480
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001785-95
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Georgia, Poland, United States

Contacts

• Name: VP, Clinical Development
• Affiliation: Biota Pharmaceuticals, Inc.

• Name: VP, Clinical Development
• Affiliation: Biota Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects, aged 18-75 years inclusive, with an established clinical history of asthma for at least one year in accordance with the definitions described by the GINA guidelines (GINA 20121 or the National Asthma Education and Prevention NAEP Diagnosis Guidelines 20072);
2. History within the previous 14 months (prior to screening) of asthma worsening or exacerbation due to presumed viral respiratory infection which required asthma rescue medication treatment;
3. Subject has moderate or severe asthma defined by their current medication regimen of taking at least a medium-dose or high-dose inhaled corticosteroid (ICS) defined as fluticasone at a dosage of at least >264 mcg daily (or equivalent dose for other inhaled ICS). The subject’s asthma medication regimen has been stable for at least 4 weeks prior to screening and for at least 2 weeks prior to Study Day 1;
4. Subject has at screening, or within the prior year, documented variable airway obstruction as indicated by an increase in FEV1 (> 12%) to short-acting bronchodilator, or positive methacholine challenge, or positive histamine challenge (PC20 <8mg/ml). For subjects without appropriate documentation at screening, or within the prior year, the procedure to document the increase in FEV1 may be performed within 3 days following the Screening visit;
5. Capable of giving written informed consent that includes compliance with the requirements and restrictions listed in the consent form. Note: signed informed consent must be on file prior to screening procedures;
6. Subject is able to understand and comply with the protocol requirements, instructions and restrictions and complete the study questionnaires in a written language they understand;
7. Female subjects who are not postmenopausal for at least 2 years or surgically sterile with complete hysterectomy or bilateral oophorectomy and male subjects, who are not surgically sterile via vasectomy, must agree to use a double barrier method of birth control, such as, a condom plus spermicidal agent (foam/gel/film/cream/suppository) from the time of randomization until 30 days after completion of study drug dosing. This includes female subjects who are using hormonal contraception. Male subjects cannot donate sperm during the study starting at day 1 and for 90 days after completion of study drug dosing.
8. Female subjects must not be breastfeeding or pregnant.
Subjects must continue to meet the previous criteria and additionally meet the following criteria at Study Day 1 in order to be eligible for randomization and study treatment:
1. Subject presents to clinic reporting symptoms of a cold (e.g., answers yes to the question, “Do you have a cold today?”) with onset such that they can be randomized and dosed preferably within 24 hours but up to a 48 hour interval from symptom onset to study treatment;
2. Subject is qualified for presumptive human rhinovirus infection by clinical exam, and the presence of each of the following Day 1 WURSS-21 symptoms at a severity of 2 or greater: runny nose, sore throat, scratchy throat, as well as a minimum WURSS-21 total symptom score on day 1 of at least 20 points;

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 456
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
1. Positive result for influenza rapid-antigen test performed on Study Day 1;
2. A fever on Day 1 of 100.4°F (38°C) or greater;
3. Subject presents at clinic on Study Day 1 with severe asthma exacerbation defined as requiring immediate treatment with systemic corticosteroids or increased doses of inhaled corticosteroids;
4. Use of systemic steroids within 30 days before Study Day 1;
5. Current use of theophylline at Screening or within 4 days of Study Day 1 and any use throughout the duration of the study;
6. Subjects with evidence of a lower respiratory infection at Study Day 1, and/or a history or current evidence of chronic obstructive airways disease, cystic fibrosis, or chronic sinusitis;
7. A medical history or current clinical evidence of significant hematological, gastrointestinal, renal, hepatic, cerebrovascular, immunologic, psychiatric or cardiovascular disease or event (including uncontrolled hypertension as determined by the Investigator), or any clinical condition, that may in the opinion of the Investigator or Medical Monitor, impact on the subject’s ability to participate in the study, the subject’s safety, or on the study results;
8. History of adverse reaction or hypersensitivity to capsid binders, or history of significant seasonal allergy within the last 3 years that in the opinion of the investigator would significantly interfere with the evaluation of asthma control or diagnosis of presumptive HRV infection;
9. Clinical laboratory values at screening for neutrophils which reflect grade 2 or higher reductions from normal range, or AST or ALT results which reflect grade 2 or higher elevations per the Common Terminology Criteria for Adverse Events (CTCAE). Screening hemoglobin value reductions of >2 gm/dL below Lower Limit of Normal (LLN). Subjects with other clinical laboratory abnormalities outside normal reference ranges will be considered for inclusion, if in the opinion of the investigator or Medical Monitor the abnormalities are not clinically significant, and will not jeopardize the safety of the subject or the validity of the study;
10. Use of cold preparations, nasal lavage preparations or sprays, or prescription or over-the-counter nasal decongestants within the 24 hours preceding completion of the Day 1 WURSS-21 and randomization and during the study. Episodic use of over-the-counter anti-cholinergics is excluded within the 24 hours preceding completion of the Day 1 WURSS-21 and randomization and during the study. Use of nasal anti-histamines is excluded for 3 days prior to randomization and during the study. Use of the anti-histamines acrivastine, brompheniramine, chorpheniramine, dimenhydrinate, and doxylamine are excluded prior to randomization on Day 1 (short-acting for 1 week and long-acting for 2 weeks) and during the study. Note: The use of new generation antihistamines, e.g. loratadine, cetirizine, desloratadine, fexofenadine, and levocetirizine, and nasal steroid preparations is allowed, if use is stable for 7 days prior to Study Day 1 and continues in a stable regimen throughout the study. Acetaminophen and NSAID use is allowed.
11. Current (at screening and Study Day 1) abuse of alcohol or any use of illicit drugs, or history of alcohol or illicit drug abuse within the preceding 2 years. Any use of marijuana within 48 hours of Day 1 and at any time during the study, unless being used for a prescribed medical reason where the medical reason itself is not exclusionary;
12. A positive p

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Asthma control following presumptive human rhinovirus (HRV) infection in moderate and severe asthma subjects, as measured by the Asthma Control Questionnaire (ACQ-6).

Intervention(s)

Product Name: Vapendavir 132 mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Vapendavir
CAS Number: 439085-51-5
Current Sponsor code: BTA798
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 132-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 14.

Primary end point(s): Change from baseline to Study Day 14 in ACQ-6 total score.

Main Objective: To evaluate the effect of vapendavir on asthma control following HRV infection, as measured by the Asthma Control Questionnaire (ACQ-6).

Secondary Objective: - To assess the safety and tolerability of vapendavir
- To assess the effect of vapendavir on symptoms of human rhinovirus infection as measured by the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), prevention of asthma exacerbations, virology outcomes including resistance monitoring, and lung function tests.
Exploratory Objective:
- To compare bilateral nasopharyngeal sampling to total blown mucus sampling for HRV detection by PCR and RVP testing methodologies.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) Study Days 1-14.
2) Study Days 1-14.
3) Study Days 7, 21 and 28
4) Study Days 1-28.
5) Study Days 1-28.
6) Post-day 1.
7) Study Day 1 to 14.
8) Study Day 1 to 14.
9) Study Days 1 to 14.
10) Study Days 1 to 14.
11) Peak infection days 2-4, 3-5, and 2-7
12) Time to alleviation (hours).
13) Study Days 1-14.
14) Study Days 1-14.
15) Study Days 1-14.
16) Study Days 1-14 and 1-28.
17) Study Days 1-14 and 1-28.
18) Study Days 1-14 and 1-28.
19) Study Days 1-14 and 1-28.

Secondary end point(s): 1) Proportion of subjects with a moderate or severe asthma exacerbation during the interval of Study Days 1-14
2) Proportion of subjects with a severe asthma exacerbation during the interval of Study Days 1-14
3) Change from baseline (Day 1) to Study Day 7, to Study Day 21, or to Study Day 28 in ACQ-6 total score
4) Proportion of subjects with at least a 0.5 point reduction in ACQ-6 score from baseline (Day 1) over the 28 days of the study
5) Proportion of subjects with at least a 0.5 point increase in ACQ-6 score from baseline (Day 1) over the 28 days of the study
6) Proportion of subjects with a post-day 1 ACQ-6 score of < 1.5
7) Daily ß2-agonist use over Study Days 1-14
8) Reliever free days over Study Days 1-14
9) Maximum fall in forced expiratory volume in 1 second (FEV1) during days 1-14 as a percent of day 1 level
10) Maximum increase in forced expiratory volume in 1 second (FEV1) during days 1-14 as a percent of day 1 level
11) WURSS-21 daily change severity score averaged over the peak infection days 2-4, 3-5, and 2-7
12) Time to alleviation (hours) of WURSS-21 cold symptoms
13) Maximum fall in peak expiratory flow (PEF) during the days 1-14 as a percent of day 1 level
14) Maximum absolute fall in peak expiratory (PEF) during days 1-14 from day 1 SABA level
15) Maximum fall in Forced Vital Capacity (FVC) during the Days 1-14, as a percent of Day 1 level
16) Proportion of patients with a % FVC decline of > 10% from Day 1 level at any time during Days 1-14, and during Days 1-28
17) Proportion of patients with a % FVC decline of > 10% from Day 1 level at any time during Days 1-14 and during Days 1-28
18) Proportion of patients with a % FEV1 decline of > 10% from Day 1 level at any time during Days 1-14, and during Days 1-28
19) Proportion of patients with a % FEV1 decline of > 10% from Day 1 level at any time during Days 1-14 and during Days 1-28

Secondary ID(s)

BTA798-203

Source(s) of Monetary Support

Biota Pharmaceuticals, Inc.