Clinical Trials Register

Summary
EudraCT Number:	2011-000117-39
Sponsor's Protocol Code Number:	A2301
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-20
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

Austria - BASG

A.2

EudraCT number

2011-000117-39

A.3

Full title of the trial

A Phase 3 randomized, double-blind, placebo-controlled study of SHB004 (10% topical azithromycin) administered locally twice daily for three consecutive days for the prevention of Borreliosis in subjects bitten by a tick.

A.3.1

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

Prevention of Borrelia infection and prevention of borreliosis through application of a gel, within three days, on the site of the tick bite

A.4.1

Sponsor's protocol code number

A2301

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	Ixodes 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	IXODES AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PAREXEL International GmbH
B.5.2	Functional name of contact point	Anke Rodenberg
B.5.3	Address:
B.5.3.1	Street Address	Waldecker Strasse 10-12
B.5.3.2	Town/ city	Moerfelden
B.5.3.3	Post code	64546
B.5.3.4	Country	Germany
B.5.4	Telephone number	+ 49 61059430 116
B.5.5	Fax number	+ 49 61059430 501
B.5.6	E-mail	anke.rodenberg@parexel.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	SHB004
D.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Azithromycin
D.3.9.1	CAS number	83905-01-5
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Gel
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Lyme borreliosis

E.1.1.1

Medical condition in easily understood language

Borreliosis

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10067559
E.1.2	Term	Lyme borreliosis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to demonstrate a reduction in the rate of treatment failure within the ITT set at Day 57 by at least 50% in response to SHB004 (10% topical azithromycin) administered locally within four calendar days after the tick bite had been first noticed, BID for three consecutive days, as compared to placebo. Treatment failure is defined as seroconversion (IgG ) and / or appearance of EM throughout the study in baseline-seronegative (IgM and IgG) subjects. Subjects experiencing an additional tick bite are not counted as treatment failure unless they experience an EM occurring before the additional tick bite.

E.2.2

Secondary objectives of the trial

Secondary objective 1 is as the primary objective for the All Treated
Subjects A-C set, and modified ITT set.
Secondary objective 2 is as the primary objective in the ITT set and
isolated IgM are not counted as Treatment Failure (TF).
Secondary objective 3 is as the primary objective in the ITT set and
isolated IgG are not counted as TF.
Exploratory objective is as the primary objective but for the PP set.

Safety: To demonstrate the local safety and tolerability of SHB004 (10% topical azithromycin) administered locally BID for three consecutive days.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed written informed consent by the subject before any study procedure is performed.
2. Males or females aged ≥ 18 years and < 80 years at screening.
3. Subjects bitten by one tick (single bite), who have extracted the tick from the skin and collected such tick or parts of the tick (e.g. hypostom), or have the tick or parts of the tick still attached to the skin, and are willing to hand it over.
4. Subjects able to receive the first study treatment administration at the latest on the 4th calendar day from the day the tick bite was first noticed (note: the day the tick bite was first noticed being counted as the first calendar day).
5. Are neither pregnant, nor breast-feeding and do not plan to become pregnant during the study. Females with childbearing potential must undergo a urine pregnancy test at screening. Please note that female subjects who have had a hysterectomy or are postmenopausal for longer than 2 years are not considered as being of childbearing potential. Pregnant or breast feeding females, or women planning to become pregnant during the study cannot participate.

E.4

Principal exclusion criteria

1. Subjects who have treated the site of the index tick bite with a topical formulation of an antibiotic other than SHB004 gel. Administration of a topical antibiotic other than SHB004 outside the area of tick bite is allowed (e.g. ophthalmic or otic applications, etc).
2. Subjects who received parenteral or oral antibiotic treatment within 10 days prior to enrollment.
3. Subjects who have a skin score according to Appendix 1 of this protocol grading 3 or worse at baseline.
4. Subjects with a history of allergic reaction or hypersensitivity to macrolide antibiotics (e.g. erythromycin, azithromycin) characterized e.g. by rash, itching, difficulty in breathing or anaphylaxis.
5. Subjects with a history of autoimmune diseases (e.g. rheumatoid arthritis or lupus erythematosus), history or clinical signs of syphilis, active herpes virus infection, subjects under immunosuppressive therapy (prescription drugs only), collagen vascular or immunodeficiency disease, or with a known active infectious mononucleosis (please note, that subjects reporting a past infection are not excluded, only those reporting a current infection).
6. Concurrent systemic steroid therapy. Inhaled steroids are allowed. Topical steroids are allowed when applied at least 10 cm apart from the index tick bite site.
7. Treatment with systemic steroids, other immunomodulatory drugs, or cytostatics within 30 days before enrollment.
8. History of Borreliosis / Lyme disease during the previous 12 months or positive test for antibodies against Borrelia s.l. (seroconverted) as assessed within the last two years prior to enrollment (only the most recent antibody test has to be taken into account; if this latest test is negative the subject is not to be excluded for this reason).
9. Subjects presenting with multiple tick bites at screening/baseline visit.
10. Subjects unable to spot the site of the index tick bite at screening/baseline visit.
11. Subjects who have a history of one or more tick bites within 60 days prior to randomization (except for the current tick bite qualifying for this study).
12. Concurrent tick-borne diseases, such as babesiosis or ehrlichiosis.
13. Any other drug allergy or condition or significant medical problem which in the opinion of the investigator places the subject at unacceptable risk or does not allow the subject to follow study procedures as planned.
14. Have received treatment with any other investigational drug, and/or have participated in another clinical study within 30 days before screening.
15. Are pregnant or a nursing mother.
16. Have a history of, or known current problems with drug or alcohol abuse. (Subject with a history of abuse [drug and/or alcohol], but who have been observing a strict abstinence for at least 1 year will be allowed to participate).
17. Have a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment.
18. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia or confused state of the subject.
19. Have previously been enrolled in this study.

E.5 End points

E.5.1

Primary end point(s)

treatment failure within the ITT set at Day 57;

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 4; Day 57

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 4; Day 57

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

LVLS

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:

2600

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

700

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-04-20.

Yes

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

825

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3300

F.4.2.2

In the whole clinical trial

3300

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)

Standard care

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

2011-06-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-05-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-12-03

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