A Phase IIa, Single-centre, Randomised, Vehicle Controlled, Double-blind Trial for Assessment of Efficacy, Safety and Tolerability of the Topical Formulation SB011 Containing a Human GATA-3 Specific DNAzyme and of Systemic Absorption of hgd40 Following Application to Lesional Skin in Patients With Atopic Eczema
Overview
- Phase
- Phase 2
- Intervention
- SB011, 2 % (Water/Oil/Water) emulsion of hgd40
- Conditions
- Mild to Moderate Atopic Dermatitis
- Sponsor
- Sterna Biologicals GmbH & Co. KG
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Change of local SCORing atopic dermatitis (SCORAD) from baseline to Day 15.
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
Atopic dermatitis (AD) is a chronic or chronic recurring inflammatory skin disorder. Patients suffer from eczema and often severe pruritus on the affected skin, as well as from frequent complications and secondary infections. Next to a genetically predetermined defect in epidermal barrier function and vegetative dysfunction, AD arises from an upregulation of Th2-modified immune responses inducing increased IgE-antibody production, cytokine secretion and subsequently, local inflammation.
Although standard therapies of AD, modern topical corticosteroids, show a better ratio of therapeutic effects to side effects, they retain a moderate acceptance due to their non-specific action, strict compliance requirements and possible adverse effects. As a newer alternative, calcineurin inhibitors show fewer side effects but raise concerns regarding long term risks including the possibility of skin carcinogenicity. Therefore, medical need remains for novel therapies for this major public health problem, directed in particular at specific early disease-causing mechanisms and/or molecular targets, with an improved efficacy, safety and compliance.
Novel therapeutic strategies for the treatment of chronic inflammatory diseases by targeting early disease-causing mechanisms are a promising approach for the treatment of AD.
The transcription factor GATA-3 represents the key regulatory factor of Th2-driven immune responses. It is indispensable for the differentiation and activation of Th2 cells; it integrates Th2 signals and induces Th2 cytokine expression. The investigational product SB011 contains the DNAzyme hgd40 that targets GATA-3. By cleaving GATA-3 mRNA hgd40 reduces specific cytokine production and thereby reduces key features of allergic airway inflammation.
DNAzymes are completely generated by chemical synthesis and can be produced under Good Manufacturing Practice (GMP) controlled conditions. The DNAzymes are not biological drugs, i.e. they are not generated by use of any living organism including cell culture or bacteria. The molecules are highly water-soluble and will be applied as a water/oil/water (W/O/W) formulation since multiple emulsions have been shown to protect the active ingredient from degradation on the skin and have penetration enhancing properties in comparison to other carrier systems.
This proof-of-concept study will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the topical formulation SB011 containing 2 % hgd40 twice daily (BID) in patients with mild to moderate atopic eczema.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient oral and written informed consent
- •Adult Caucasian patients (male and female) aged 18-69 years (both included);
- •Patients smoking ≤ 10 cigarettes/day
- •Patient has confirmed diagnosis of atopic dermatitis using the diagnostic features as described by Hanifin and Rajka, initial diagnosis made at least 12 weeks before first treatment;
- •SCORAD (12) between 20 and 50 (mild to moderate atopic dermatitis);
- •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;
- •Patient has to have an increased total IgE;
- •Patient has to have an increased specific IgE of at least 1 of the sx1 allergens with CAP classification II \[\>0.7 KU/l\];
- •Erythema score from modified local SCORAD for both lesional areas of at least 2;
- •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);
Exclusion Criteria
- •History of allergic reactions to any active or inactive component of the IMP;
- •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, influence the results of the trial or the patient's ability to take part in it;
- •Inherent or acquired immune deficiency, immune deficiency in consequence of drug use;
- •Immune mediated diseases;
- •Suntan, hyperpigmentation or tattoos in the test fields;
- •Dark-skinned persons whose skin colour prevents ready assessment of skin reactions;
- •Systemic bacterial or mycotic as well as severe viral systemic infections;
- •Severe systemic other disease;
- •Patients with a resting heart rate \<50 and \>100 bpm, systolic blood pressure \<100 and \>150 mmHg, diastolic blood pressure \<60 and \>95 mmHg;
- •UV-therapy within 6 weeks before first treatment and during the trial;
Arms & Interventions
SB011, 2 % (Water/Oil/Water) emulsion of hgd40
All patients will perform treatment with formulation SB011 containing 2 % hgd40 and the active ingredient-free vehicle. The comparison of the IMPs will be performed intraindividually. Comparison and random assignment of treatments to two distinct treatment areas (area 1, area 2). IMP SB011: Topical application of approximately 5 mg/cm2 (250 μl) per treatment area (50 cm2) twice daily on 14 consecutive days, one single last application at the site on Day 15 (29 treatments) daily dosage: Approximately 10 mg hgd40 total dosage: Approximately 145 mg hgd40
Intervention: SB011, 2 % (Water/Oil/Water) emulsion of hgd40
Multiple W/O/W formulation, active ingredient-free vehicle
All patients will perform treatment with formulation SB011 containing 2 % hgd40 and the active ingredient-free vehicle. The comparison of the IMPs will be performed intraindividually. Comparison and random assignment of treatments to two distinct treatment areas (Area 1, Area 2). Vehicle: Topical application of approximately 5 mg/cm2 (250 μl) per treatment area (50 cm2) twice daily on 14 consecutive days, one single last application at the site on Day 15 (29 treatments)
Intervention: Multiple W/O/W formulation, active ingredient-free vehicle
Outcomes
Primary Outcomes
Change of local SCORing atopic dermatitis (SCORAD) from baseline to Day 15.
Time Frame: On baseline (day 1) and on day 15 (Last day after 2 Weeks IMP administration)
The following parameters are included in scoring: A: the extent of the involved body area; B: the intensity of the criteria erythema, edema/papulation, oozing/crusts, excoriations,lichenification and dryness, whereby dryness is evaluated on uninvolved areas; C: the subjective symptoms of pruritus at application areas and sleep loss evaluated on a visual analogue scale from 0 to 10 (average for the last three days or nights) and added. The intensity of each of the criteria erythema, edema/papulation, oozing/crusts, excoriations, lichenification and dryness will be graded according to the following 4 point scale: 0 = absent 1. = mild 2. = moderate 3. = severe Each single parameter for SCORAD calculation will be documented on a source document. The SCORAD will be calculated according to the formula A/5 + 7B/2 + C and documented in the source documents and the CRF.
Secondary Outcomes
- The change from baseline in modified local SCORAD(On Days 3, 5, 8, and 12)
- Modified local SCORAD(on Days 1, 3, 5, 8, 12, and 15)
- Change from baseline in transepidermal water loss (TEWL)(On Days 3, 5, 8, 12, and 15)
- TEWL on Days 1, 3, 5, 8, 12, and 15(Days 1, 3, 5, 8, 12, and 15)
- Pharmacokinetic outcome measure(Day 1 and Day 15)
- Physical examination of the skin and Vital signs(Screening period and day 16)
- Subjective assessment of pruritus using a 10-point rating scale(Days 1, 3, 5, 8, 12, and 15)
- Subjective efficacy assessment on Days 3, 5, 8, 12 and 15(Days 3, 5, 8, 12 and 15)
- Subjective dermal tolerability assessment using a 5-point rating scale on Days 3, 5, 8, 12 and 15(Days 3, 5, 8, 12 and 15)
- Adverse Events(Including the whole screening period and the experimental phase day -14 to day 16)
- Standard Safety laboratory(Screening period + on days 1, 5 and 16 in the Treatment period)