Clinical Trials Register

Summary
EudraCT Number:	2012-000442-35
Sponsor's Protocol Code Number:	CS-BM32-003
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-21
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

Germany - PEI

A.2

EudraCT number

2012-000442-35

A.3

Full title of the trial

PHASE II STUDY ON THE SAFETY AND EFFICACY OF BM32,
A RECOMBINANT HYPOALLERGENIC VACCINE FOR IMMUNOTHERAPY OF GRASS POLLEN ALLERGY

A.3.1

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

STUDY ON THE SAFETY AND EFFICACY OF BM32,
A VACCINE FOR IMMUNOTHERAPY OF GRASS POLLEN ALLERGY

A.4.1

Sponsor's protocol code number

CS-BM32-003

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	Biomay AG
B.1.3.4	Country	Austria
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	Biomay AG
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Biomay AG
B.5.2	Functional name of contact point	Head of Product Development
B.5.3	Address:
B.5.3.1	Street Address	Lazarettgasse 19
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	004317966296101
B.5.5	Fax number	004317966296222
B.5.6	E-mail	a.neubauer@biomay.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	BM32 (4 API components)
D.3.2	Product code	BM32/S2
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM321
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM322
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM325
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM326
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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.IMP: 2
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	BM32 (4 API components)
D.3.2	Product code	BM32/S3
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM321
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM322
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM325
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BM326
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Suspension for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Grass pollen allergy

E.1.1.1

Medical condition in easily understood language

Grass pollen allergy

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10048908
E.1.2	Term	Seasonal allergy
E.1.2	System Organ Class	10021428 - Immune system disorders

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 assess the sustained clinical effect of BM32 during 2 consecutive treatment years compared to placebo. The clinical effect of 2 different dose levels of BM32 is evaluated by a combined Symptom-Medication-Score (SMS) which is recorded during the peak of the grass pollen season of each treatment year.

E.2.2

Secondary objectives of the trial

•Clinical effect of BM32 as evaluated by SMS recorded during the whole grass pollen season
• effect of BM32 on level of allergy symptoms (SS) and medication needed (MS) during the peak &the whole grass pollen season
•Effect of BM32 on individual allergy symptoms by comparing scores (BM32-treated vs. placebo)
•Effect of treatment with BM32 on the “Well-being” of subjects during the grass pollen season by VAS.
•Number of “bad days” and Number of “symptom-free” days during the pollen season
•Effect of treatment with BM32 vs. placebo on the skin reactivity to a commercially available grass pollen extrac, as measured by titrated SPT
•effect of treatment with BM32 via a Rhinoconjunctivitis-Quality-of-Life-Questionnaire (RQLQ)
•potential effect of treatment with BM32 on asthma symptoms
•Development of Immunological parameters (specific IgG and IgE) during treatment
•effects of subcutaneous administration of BM32 on parameters of vital signs and safety laboratory parameters

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

In(1). Positive history of grass pollen allergy, positive skin prick test reaction to grass pollen extract, grass pollen allergen-specific IgE and rPhl p 1/rPhl p 5-specific IgE (at least 3.5 kUA/L) at the at the screening visit or within 12 months prior to the screening visit.
In(2). Moderate to severe symptoms of grass pollen allergy during pollen peak in the baseline period (exact definition of this criterion is specified in the study reference manual (SRM))
In(3). Age between 18 and 60 years (m/f)
In(4). Subjects must have a standard health care insurance
In(5). Subject must appear capable to understand and comply with all relevant aspects of the study protocol
In(6). Subject must be available during the study period to complete all treatments and assessments

E.4

Principal exclusion criteria

Ex(1). symptomatic perennial allergies or symptomatic seasonal co-allergies during the grass pollen season
Ex(2). atopic dermatitis
Ex(3). pregnancy or breast feeding
Ex(4). women with childbearing potential who are not using a medically accepted birth control method
Ex(5). autoimmune diseases, immune defects including immuno- suppression, immune-complex-induced immunopathies
Ex(6). contra-indication for adrenaline
Ex(7). severe general maladies, malignant diseases
Ex(8). patients under long-term treatment with systemic corticosteroids, immuno-suppressive drugs, tranquilizers or psychoactive drugs
Ex(9). contra-indications for skin prick testing such as: skin inflammation in the test area, urticaria facticia.
Ex(10). asthma not controlled by low dose inhaled corticosteroids. This means that Patients with a history of concomitant asthma should have a FEV1 > 70% at inclusion. Patients without a history of asthma should have FEV1 >70% or a PEF > 80% at inclusion
Ex(11). Chronic use of beta-blockers
Ex(12). participation in another clinical trial within one month prior to the study; however, participation during the previous month solely in the form of blood donation and/or without other interventions will be acceptable
Ex(13). patients who participated in a pollen SIT trial or received marketed pollen SIT in 2 years prior to study
Ex(14). patients who had a previous grass pollen SIT or have participated in a clinical trial of grass pollen SIT
Ex(15). risk of non-compliance with the study procedure and restrictions (e.g. with alcohol, drug or medication abuse within the past year)
Ex(16). Use of prohibited medication prior to Screening (Visit 1) and throughout the study:
o Depot corticosteroids – 12 weeks prior to V1
o Oral corticosteroids – 8 weeks prior to V1
o High –dose inhaled corticosteroids – 4 weeks prior to V1
Ex(17). Use of anti-histamines three days prior to V1 or V2
Ex (18). patients with nasal polyposis
EX (19). patients sensitized to phl p 7 (specific IgE to Phl p 7 and/or Bet v 4 > 0.35 kUA/L

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint
There will be two main efficacy endpoints tested simultaneously:
• The mean daily combined symptom-medication-score (SMS) in patients receiving BM32 during the grass pollen peak measured in treatment year 1. • The mean daily combined symptom-medication-score (SMS) in patients receiving BM32 during the grass pollen peak measured in treatment year 2.

Primary Safety Endpoint
• Frequency of AEs concerning occurrence, seriousness, intensity and relationship to study drug.
• Frequency and grading of local reactions (injection site reactions) and systemic reactions.

E.5.1.1

Timepoint(s) of evaluation of this end point

primary efficacy:
peak of the grass pollen season in treatment year 1 and treatment year 2
(peak period will be determined on actual pollen count data for each year for each center retrospectively)

primary safety: evaluated during the whole trial

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoint(s)
• The mean daily SMS during the whole grass pollen season measured in treatment years 1 and 2 comparing the two BM32 verum doses with placebo.
• The mean daily Symptom-Score (SS), and Medication-Score (MS) during the peak of the pollen season measured each in treatment years 1 and 2 comparing the two BM32 verum doses with placebo.
• The mean daily SS and MS during the whole pollen season measured in treatment years 1 and 2 each comparing the two BM32 verum doses with placebo.
• Mean of each individual symptom of the SS measured in treatment years 1 and 2:
o BM32-treated patients compared to placebo
o during pollen peak and the whole pollen season

• Mean level of “well-being” during the grass pollen season of patients receiving BM32 compared to placebo based on daily records on a visual analogue score (VAS) measured in treatment years 1 and 2.
• Number of “bad days” (i.e. days with at least one symptom categorized as “severe” ) during the whole grass pollen season and during the grass pollen peak measured each in treatment year 1 and 2 comparing the two BM32 verum doses with placebo.
• Number of symptom-free days (i.e. days with no symptoms of disease (SS=0)) of patients receiving BM32 compared to placebo during the whole grass pollen season and during grass pollen peak measured in treatment years 1 and 2 each.
• Change in skin reactivity to a commercially available grass pollen extract as determined by titrated SPT (dose titration of grass pollen extract) in patients receiving BM32 compared to placebo by
o comparing treatment year 1 and 2 each to baseline
o comparing skin reactivity as measured at different time points during the study (Visits 2,3,5,8,9,12,15, and 16).
• Mean Quality of Life score as measured via RQLQ in patients receiving BM32 compared to placebo in treatment years 1 and 2 each.
The RQLQ will be included in the electronic diary and measured in treatment years 1 and 2
• Mean asthma score measured during treatment years 1 and 2 (grouped by whole grass pollen season and grass pollen peak period) comparing BM32 treated patients with placebo treated patients.

Secondary Safety and Immunogenicity Endpoint(s)
Vital signs and physical examination
• Blood pressure, pulse rate, body temperature, and breathing frequency, and findings of physical examination at screening (V1), medication phase (V5-7, V10, V12-14) and at the follow-up examination (V17)
Safety Laboratory
• Hematology, blood biochemistry, and urine analysis at screening (V1), before IMP administration at V5 and V12 and at the follow-up examination (V17).
Immunogenicity
• Mean allergen-specific and PreS-specific antibodies (IgG and IgE) as measured at different time points during the study (Visits 2,3,5,8,9,10,11,12,15,16, and 17) compared between verum treated and placebo treated patients.

E.5.2.1

Timepoint(s) of evaluation of this end point

•mean daily SMS: during whole grass pollen season (GPS) in treatment years 1&2
•mean SS, and MS and indiv.SS symptoms: during peak&whole GPS in treatment years 1&2
•Mean level of “well-being” by VAS: during GPS in treatment years 1&2
•No.“bad days”, No.“symptom free days”: during the whole GPS and grass pollen peak in treatment year 1&2
•Change in skin reactivity: comparing treatment year 1&2 each to baseline, and comparing skin reactivity measured at Visits 2,3,5,8,9,12,15, and 16.
•Mean Quality of Life via RQLQ: in treatment years 1&2
•Mean asthma score: measured during treatment years 1&2
•Vital signs and Physical examination: Visits1, 5-7, 10, 12-14,17
•Safety Lab: Visits 1, 5, 12,17
•(IgG&IgE) Visits 2,3,5,8,9,10,11,12,15,16,17

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

end of trial is defined as "data base 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:

180

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

180

F.4.2.2

In the whole clinical trial

180

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All subjects who end their participation in the trial will continue to be monitored by their respective physicians, using standard medical care. No special procedures or extra medical care is needed after the trial that would not be otherwise used in patients who have not participated in the trial.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-18

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