E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067559 |
E.1.2 | Term | Lyme borreliosis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
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 (IgM and / or IgG) and / or appearance of EM throughout the study in baseline-seronegative (IgM and / or 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. |
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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. |
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E.2.3 | Trial contains a sub-study | No |
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.
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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.
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E.5 End points |
E.5.1 | Primary end point(s) |
treatment failure within the ITT set at Day 57; |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |