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] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
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 is to evaluate efficacy of the topical formulation SB011 containing 2 % hgd40 on lesional skin by clinical assessment of skin condition in patients with mild to moderate atopic eczema
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety, tolerability and pharmacokinetic profile of the topical formulation SB011 containing 2 % hgd40 in patients with mild to moderate atopic eczema |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optionally for potential future scientific analyses, biopsies may be taken in two subgroups of up to five voluntary patients (one 4 mm biopsy from each treated area at the end of treatment). |
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E.3 | Principal inclusion criteria |
All of the following criteria have to be met for inclusion of a patient in this trial:
1. Patient has been informed both verbally and in writing about the objectives of the clinical trial, the methods, the anticipated benefits and potential risks and the discomfort to which he/she may be exposed, and has given written consent to participation in the trial prior to trial start and any trial-related procedure;
2. Adult Caucasian patients (male and female) aged 18-69 years (both included);
3. Patients smoking ≤ 10 cigarettes/day;
4. Patient has confirmed diagnosis of atopic dermatitis using the diagnostic features as described by Hanifin and Rajka (6), initial diagnosis made at least 12 weeks before first treatment;
5. SCORAD (12) between 20 and 50 (mild to moderate atopic dermatitis);
6. Two comparable lesional areas of approximately 50 cm2 each (difference in modified local SCORAD not greater than 2) on the arms, legs, chest, stomach or neck (distance between the lesions at least 5 cm), clinical condition of atopic eczema mild to moderate defined by a modified local SCORAD between 7 and 10 with 2 parameters scored at least 2 one being the erythema score;
7. Patient has to have an increased total IgE;
8. Patient has to have an increased specific IgE of at least 1 of the sx1 allergens with CAP classification II [>0.7 KU/l];
9. Erythema score from modified local SCORAD for both lesional areas of at least 2;
10. TEWL in the lesional areas at least 12 g/m²h, TEWL value differences ≤ 30 % are allowed between both lesional areas (related to the higher TEWL value);
11. Except for atopic diseases or asthma like atopic dermatitis or allergic rhinitis assessed as healthy based on a screening examination including medical history, physical examination of the skin, vital signs, and clinical laboratory results;
12. The male patient must agree:
- to use two methods of contraception in combination with his female partner, if she is of childbearing potential; this combination of contraceptive methods must be used from screening until at least 6 months after the last dose of IMP. At least one of the contraception methods must be a barrier contraception method. Contraceptive methods allowed include the following: condoms, as well as for female partner’s diaphragm in combination with a spermicide, intrauterine device, oral contraception, contraception implants, OR
- not to be sexually active at screening and accept using double-barrier contraception should he become sexually active during the trial or within 6 months after the last dose of IMP, OR
- to have been surgically sterilised prior to screening and accept to use a barrier method of contraception as well, OR
- to have a partner who is post-menopausal and has had her last natural menstruation at least 12 months prior to screening, OR
- to have a partner who has had a hysterectomy prior to screening, OR
- to have a partner who has been surgically sterilised prior to screening;
13. The female patient must agree:
- to use two methods of contraception in combination with her male partner, if she is of childbearing potential; this combination of contraceptive methods must be used from screening until at least 6 months after the last dose of IMP. At least one of the contraception methods must be a barrier contraception method. Contraceptive methods allowed include the following: condoms, as well as for female partner’s diaphragm in combination with a spermicide, intrauterine device, oral contraception, contraception implants, OR
- not to be sexually active at screening and accept using double-barrier contraception should she become sexually active during the trial or within 6 months after the last dose of IMP, OR
- to have been surgically sterilised prior (hysterectomy or tubal ligation) to screening and accept to use a barrier method of contraception as well, OR
- to be post-menopausal (at least since 12 months or six months amenorrhoea with FSH serum >40 mU/ml).
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E.4 | Principal exclusion criteria |
Patients are to be excluded from the trial, when one or more of the following conditions are met:
1. History of allergic reactions to any active or inactive component of the IMP;
2. Presence of clinically significant diseases other than asthma or atopic diseases (cardiovascular, renal, hepatic, gastrointestinal, haematological, neurological, genitourinary, autoimmune, endocrine, metabolic, etc.), which, in the opinion of the investigator, may either put the patient at risk because of participation in the trial, or diseases which may influence the results of the trial or the patient’s ability to take part in it;
3. Inherent or acquired immune deficiency, immune deficiency in consequence of drug use;
4. Immune mediated diseases;
5. Suntan, hyperpigmentation or tattoos in the test fields;
6. Dark-skinned persons whose skin colour prevents ready assessment of skin reactions;
7. Systemic bacterial or mycotic as well as severe viral systemic infections;
8. Severe systemic other disease;
9. Patients with a resting heart rate <50 and >100 bpm, systolic blood pressure <100 and >150 mmHg, diastolic blood pressure <60 and >95 mmHg, on condition that the patient does not present any clinical symptoms of hypotension;
10. UV-therapy within 6 weeks before first treatment and during the trial;
11. History or current evidence of a malignant tumour (an excised basal cell carcinoma distant from target lesion with at least 14 days after surgery will be allowed);
12. Clinically relevant abnormalities in serology, clinical chemical, haematological or in any other laboratory variables;
13. Chronic or acute infections (a small lesion of non-treated onychomycosis will be allowed in the opinion of the investigator);
14. Pregnancy or nursing
15. Signs of secondary infections on the lesions to be treated;
16. History of previous administration of SB011 or any other registered or investigational oligonucleotide-based drug;
17. History or presence of alcohol or drug abuse;
18. Consumption of alcohol within 48 h before administration of IMPs and during the trial;
19. Use of any medication (including over-the-counter medication such as herbal products) except allowed concomitant medication within 2 weeks (for biologics: 6 months, for systemic treatment of atopic dermatitis 4 weeks) before administration of the IMPs or within <10 times the elimination half-life of the respective drug, or the duration of the pharmacodynamics effect, whatever is longer, or anticipated concomitant medication during the treatment period (exception: asthma may be found in patients with AD, therefore the continuation of inhalative treatment with corticosteroids in patients with asthma accompanying AD that began at least four weeks prior to randomisation will be allowed; dose limited: ≤ 300 µg/d fluticasone propionate or equivalent);
20. Treatment with known cytochrome P450 enzyme inducing or inhibiting agents (St. John’s Wort (“Johanniskraut”), barbiturates, phenothiazines, cimetidine, ketoconazole) within 30 days before administration of the IMPs or during the trial;
21. Consumption of grapefruit, grapefruit juice within 14 days prior to the IMP administration or during the trial;
22. Need for additional skin care products in the treatment area(s);
23. Use of skin care products with anti-septic components during the last four weeks before first treatment and during the trial or anti-septic textiles with contact to the target lesions;
24. Proneness to orthostatic dysregulation, faintings, or blackouts;
25. Planned donation of germ cells, blood, organs, bone marrow during the course of the trial or within 6 months thereafter;
26. Participation in another clinical trial with an investigational drug or device within the last 3 months. For biologics, the minimum exclusion period is at least 6 months or the time of duration of the pharmacodynamics effect or 10 times the half-life of the respective drug whatever is longer before inclusion in this trial;
27. Lack of ability or willingness to give informed consent;
28. Anticipated non-availability for trial visits/procedures;
29. Anticipated lack of willingness or inability to cooperate adequately;
30. Close affiliation with the investigators (e.g. a close relative) or persons working at bioskin GmbH or persons working at the study site or employees of sterna biologicals GmbH & Co. KG;
31. Vulnerable patients (e.g., persons kept in detention).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary enpoint is comparison of active IMP vs. vehicle with respect to the change from baseline in modified local SCORAD on Day 15. |
Der primäre Endpunkt ist ein Vergleich zwischen dem aktiven IMP mit dem Vehikel unter Berücksichtigung der Veränderung zur Baseline bei dem modifizierten lokalem SCORAD an Tag 15 |
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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) |
The secondary objective of this trial is to evaluate the safety,
tolerability and pharmacokinetic profile of the topical formulation
SB011 containing 2 % hgd40 in patients with mild to moderate atopic
eczema |
Beurteilung der Sicherheit, Verträglichkeit und das
pharmakokinetische Profil der topischen Formulierung SB011,
welche 2 % hgd40 enthält, bei Patienten mit milden bis moderaten
atopischen Ekzemen |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
complete Treatment period |
über die komplette Behandlungsdauer |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 1 |
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 | No |
E.8.5 | The trial involves multiple Member States | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |