Clinical Trials Register

Summary
EudraCT Number:	2009-013429-40
Sponsor's Protocol Code Number:	CVAK694A2205
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-09-11
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

UK - MHRA

A.2

EudraCT number

2009-013429-40

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled trial to determine the capacity of VAK694 to elicit long term immune tolerance when combined with subcutaneous allergen immunotherapy for the treatment of seasonal allergic rhinitis

A.4.1

Sponsor's protocol code number

CVAK694A2205

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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.3.2	Product code	VAK694
D.3.4	Pharmaceutical form	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	VAK694
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	150
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	Anti-IL 4 antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Alutard Avanz Treatment Initiation Package
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK Abello S/A
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Alutard Avanz
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	0
D.3.9.3	Other descriptive name	PHLEUM PRATENSE L.
D.3.10	Strength
D.3.10.1	Concentration unit	SQU/ml Standardised Quality Unit(s)/millilitre (Deprecated)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1,000 to 100,000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Powder and solvent for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution 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

Seasonal allergic rhinitis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10001723
E.1.2	Term	Allergic rhinitis

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 induction of sustained tolerance to allergen when VAK694 with a dosing regimen given every 4 weeks for a total of 4 doses is combined with subcutaneous immunotherapy for the treatment of moderate to severe grass-pollen allergy as measured by the Late Phase Response.

• To assess the safety and tolerability of VAK694 when administered in the context of SCIT

E.2.2

Secondary objectives of the trial

• To evaluate the immunomodulatory activity of VAK694 as evidenced by induction of regulatory T cells, down regulation of Th2 cells, decrease in the seasonal rise in allergen-specific IgE, induction of specific antigen-binding neutralizing antibodies (IgG4), and inhibition of facilitated antigen binding (FAB)
• To assess the effects of VAK694 combined with SCIT on the symptoms of seasonal allergic rhinitis, measured by the mini-Respiratory Quality of Life Questionnaire (RQLQm) and visual analogue scale (VAS)
• To preliminarily assess the ability of VAK694 to reduce the side-effects of SCIT
• To preliminarily assess the effects of VAK694 on sustained antibody responses to immunization

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects must have a history of atopy, defined as a history of seasonal allergic rhinitis for at least 2 years (in relation to the grass pollen allergy season), and evidence of atopy, defined as a positive skin prick test (wheal difference allergen – negative control at least 3 mm) to grass pollen allergen at screening.
2. Male or female subjects aged between 18 and 60 years (inclusive) and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram and laboratory tests.
3. Female subjects must be of non-childbearing potential (women who are postmenopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Last menstrual bleeding or surgical sterilization procedures (clinical documentation required) must be noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
4. Male subjects must be using two highly effective methods of contraception, (e.g. a barrier method condom or occlusive cap plus spermicide) plus ensure use by the female partner of a second method of contraception. These measures should be in place and males should refrain from fathering a child in the three (3) months following he last study drug administration.
5. Subjects must weigh at least 50 kg with a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).
6. Able to communicate well with the investigator, to understand and comply with the requirements of the study.
7. Subjects must have provided written informed consent prior to study participation.

E.4

Principal exclusion criteria

1. Treatment with intranasal corticosteroids within 28 days prior to the first dose.
2. History of asthma with treatment with inhaled or systemic corticosteroids within 6 months of the first dose. Intermittent treatment with inhaled beta2-agonist therapy permitted.
3. History of chronic obstructive pulmonary disease (COPD).
4. Smokers with a smoking history of > 10 pack/years or anything other than casual smoking during the past year. Urine cotinine levels will be measured during screening and at baseline for all subjects. Active smokers will be defined as any subject who reports regular tobacco use and/or who has a urine cotinine considered positive according to local lab ranges.
5. Use of prescription drugs such as inhaled or oral corticosteroids and leukotriene antagonists within four (4) weeks prior to dosing, and during the study i.e. from screening to end-of-season-1 visit in Season 1 and from baseline through end-of-study visit in Season 2. Use of paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. Subjects will be allowed to use antihistamine eye drops, antihistamines, inhaled beta2 agonist therapy, and nasal steroids only as rescue medications during the season, as per section 6.6.3, and must not use these treatments on a regular basis during the study. The use of other prescription drugs during the study could be considered and should be discussed between the investigator and Novartis.
6. Participation in any clinical investigation within 4 weeks prior to first dose, or longer in the case of treatment with a drug with a longer half-life.
7. Any exposure to human monoclonal or polyclonal antibodies.
8. Any allergy immunotherapy within 3 year prior to screening.
9. Any prior grass pollen allergy immunotherapy.
10. Donation or loss of 400 mL or more of blood within 12 weeks prior to first dose.
11. Significant illness within two weeks prior to first dose.
12. Recent febrile illness within four weeks prior to first dose.
13. Symptoms of moderate to severe perennial allergic rhinitis.
14. FEV1 < 70% of predicted at screening or baseline.
15. A history of clinically significant ECG or cardiac abnormalities.
16. History of clinically significant drug allergy. A known hypersensitivity to the study drug or drugs similar to the study drug such as monoclonal antibodies.
17. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
18. History of autoimmune disease.
19. Prior history of tuberculosis or a positive test for tuberculosis at screening (differentiated from previous BCG immunization)
20. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) test result.
21. History of drug or alcohol abuse within the 12 months prior to first dose or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
22. Any active or chronic bacterial, viral, fungal, or parasitic infections
23. History of cancer, other than basal cell carcinoma of the skin
24. Concurrent administration of live vaccines should be avoided for three months prior to administration of first dose and up to three months after administration of the last dose of VAK694/placebo.

E.5 End points

E.5.1

Primary end point(s)

Primary end point is the ability of VAK694 to provide sustained suppression of the late phase cutaneous response to allergen as a reflection of long term specific immune tolerance to allergen.

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

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

Information not present in EudraCT

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

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	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	39
F.4.2	For a multinational trial
F.4.2.1	In the EEA	39
F.4.2.2	In the whole clinical trial	39

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

2009-10-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-10-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-10-20

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