Clinical Trials Register

Summary
EudraCT Number:	2014-001785-95
Sponsor's Protocol Code Number:	BTA798-203
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-31
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2014-001785-95

A.3

Full title of the trial

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.

Multicentrická, randomizovaná, dvojitě zaslepená, placebem kontrolovaná klinická studii fáze 2 s různými dávkami Vapendaviru u dospělých se středním až těžkým astmatem s příznaky rinovirové infekce.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Klinická studie s různými dávkami Vapendaviru u dospělých se středním až těžkým astmatem s infekčním nachlazením.

A.3.2

Name or abbreviated title of the trial where available

Phase 2 Asthma

A.4.1

Sponsor's protocol code number

BTA798-203

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Biota Pharmaceuticals, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Biota Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Biota Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	VP, Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	2500 Northwinds Parkway, Suite 100
B.5.3.2	Town/ city	Alpharetta, GA
B.5.3.3	Post code	30009
B.5.3.4	Country	United States
B.5.4	Telephone number	+16782213343
B.5.6	E-mail	a.barry@biotapharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vapendavir 132 mg capsules
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vapendavir
D.3.9.1	CAS number	439085-51-5
D.3.9.2	Current sponsor code	BTA798
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	132
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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

E.1.1.1

Medical condition in easily understood language

Asthma control following common cold infection in moderate and severe asthma subjects.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

- 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.

E.2.3

Trial contains a sub-study

E.3

Principal 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;

E.4

Principal 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 pregnancy test at screen;
13. Received an investigational drug or investigational vaccine within 30 days or 5 half-lives (whichever is longer), received vapendavir at any time, or use of an investigational medical device within 30 days prior to the screening visit or in the interval between screening and Study Day 1;
14. Subjects who have used any drugs or substances known to be moderate or severe inhibitors, inducers, or sensitive substrates with a narrow therapeutic range of the CYP2C19 and CYP3A4 enzymes may not be used within 5 half-lives prior to Study Day 1 or throughout the study (e.g. verapamil, erythromycin, omeprazole, fluconazole, clarithromycin, itraconazole, ketoconazole, nefazodone, fluvoxamine, carbamazepine, grapefruit juice). Reference protocol section 7.10.1 for a more extensive list of medications to be excluded.
Note: Subjects will be asked to additionally refrain during the 7-day dosing period of the study from any food or drink/beverage containing grapefruit or grapefruit juice.

15. Subjects who have a BMI >40 at Day 1.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to Study Day 14 in ACQ-6 total score.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 14.

E.5.2

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

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Georgia

United States

E.8.7

Trial has a data monitoring committee

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

Database lock.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception