Clinical Trial Results:
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
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Summary
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EudraCT number |
2013-001091-38 |
Trial protocol |
DE |
Global end of trial date |
03 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Aug 2021
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First version publication date |
04 Aug 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SB011/02/2013
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Sterna biologicals GmbH & Co KG
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Sponsor organisation address |
Bismarckstraße 7, Marburg, Germany, 35037
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Public contact |
Clinical Trial Manager, Sterna biologicals GmbH & Co KG, clinicaltrials@sterna-biologicals.com
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Scientific contact |
Clinical Trial Manager, Sterna biologicals GmbH & Co KG, clinicaltrials@sterna-biologicals.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jun 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate efficacy of the topical formulation SB011 containing 2% hgd40 on skin lesions by clinical assessment of skin condition in patients with mild to moderate atopic eczema.
For each patient, 2 preferably disseminated and contralateral, comparable skin lesions (treatment areas each 50 cm²) located on the arms, legs, chest, stomach, or neck were examined. All patients received both treatments at the same time i.e. formulation SB011 containing hgd40 and placebo. The test areas were treated for 14 consecutive days and one single last application on Day 15 (overall 29 treatments).
The investigational product SB011 contains the DNAzyme hgd40 (new class of antisense oligonucleotide therapeutics), which targets the mRNA of the transcription factor GATA-3. GATA-3 is the key regulatory factor of T helper cells 2 (Th2)-driven immune responses. The formulation SB011 - containing hgd40 - represents a novel therapy for patients with atopic dermatitis (AD).
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Protection of trial subjects |
This trial was conducted in accordance with the ethical principles that have their origin in the currently valid Declaration of Helsinki, and are consistent with ICH-GCP (January 1997) and applicable regulatory requirements.
All laboratory tests and procedures used during the study are well established and validated. Adverse events were monitored from the time of signing the informed consent to the end of the study (or study discontinuation).
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Background therapy |
- | ||
Evidence for comparator |
Abbreviations and special terms used in this entry: AD=Atopic dermatitis Baseline(Day 1)=Last observation collected prior to application of first dose of study drug. AE=Adverse event hgd40=Human GATA-3-specific DNAzyme IMP=Investigational medicinal product SAE=Serious adverse event SCORAD=SCORing atopic dermatitis (a clinical tool for assessing the severity (i.e., extent, intensity) of AD); SCORAD evaluates the severity of the atopic lesions based on affected body area and intensity of plaque characteristics SES=Safety evaluation set TEWL=Transepidermal water loss Th2=T helper cells 2 W/O/W=Water/Oil/Water (a continuous aqueous phase emulsions inside which droplets of oil contain a secondary aqueous phase i.e. double emulsion | ||
Actual start date of recruitment |
17 Feb 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 25
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Worldwide total number of subjects |
25
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EEA total number of subjects |
25
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
25
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrolled into this trial were adults with confirmed diagnosis of atopic dermatitis (AD), as defined by Hanifin and Rajka*, and with a SCORAD score between 20 and 50 (representing mild to moderate atopic dermatitis). *Diagnostic features of atopic dermatitis. Hanifin JM, Rajka G. Acta Derm Venereol Suppl (Stockh) 1980; 92:44–7 | ||||||||||||
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Pre-assignment
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Screening details |
Overall, 25 adult male and female subjects (20 to 52-years-old) with atopic dermatitis (AD), were eligible for enrolment into the trial. Subjects were screened according to inclusion and exclusion criteria. Written informed consent was obtained from patients prior to participation in the study. | ||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||
Blinding implementation details |
The IMPs were blinded and supplied by the manufacturer as patient-specifically packaged kits. The treatment test field areas were numbered as 1 and 2. Each kit contained 6 tubes of IMP 1 and 6 tubes of IMP 2. The IMPs 1 and 2 were randomly assigned the codes A and B. For each random number/patient the IMP coded A was applied on test field 1 and the IMP coded B was applied on test field 2. The comparison of the IMPs was performed intraindividually.
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Arms
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Arm title
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SB011 and Placebo | ||||||||||||
Arm description |
All patients performed treatment with formulation SB011 containing hgd40 and placebo. Treatment was performed on 2 test areas preferably disseminated and contralateral, comparable lesional treatment areas (each 50 cm²), located on the arms, legs, chest, stomach, or neck. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
SB011
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Investigational medicinal product code |
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Other name |
hgd40
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Pharmaceutical forms |
Cutaneous suspension
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Routes of administration |
Topical
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Dosage and administration details |
SB011
Topical multiple water/oil/water (W/O/W) formulation of SB011, containing 2% hgd40 in total; daily dosage was approximately 10 mg hgd40 (total dosage: approximately 145 mg hgd40).
Topical application of approximately 5 mg/cm² W/O/W formulation per treatment area (50 cm²) twice daily on 14 consecutive days and one single last application at the site on Day 15.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cutaneous emulsion
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Routes of administration |
Topical
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Dosage and administration details |
Placebo
Active ingredient-free vehicle; Water/Oil/Water emulsion.
Topical application of approximately 5 mg/cm² W/O/W formulation per treatment area (50 cm²) twice daily on 14 consecutive days and one single last application at the site on Day 15.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
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End points reporting groups
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Reporting group title |
SB011 and Placebo
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Reporting group description |
All patients performed treatment with formulation SB011 containing hgd40 and placebo. Treatment was performed on 2 test areas preferably disseminated and contralateral, comparable lesional treatment areas (each 50 cm²), located on the arms, legs, chest, stomach, or neck. | ||
Subject analysis set title |
SB011
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The evaluation of efficacy was performed for the valid cases set (VCS), which is equivalent to the intention-to-treat analysis set. The VCS included all randomised patients without any major protocol violation, i.e. violations that would interfere with the primary analysis, as shown below.
Major protocol violation:
• Violation of inclusion criteria;
• Application of any interfering concomitant medication;
• Application of less than 60 % or more than 145% of the full planned IMP amount (7.25 g), i.e. less than 4.35 g or more than 10.51 g, of any of the two IMPs;
• Missing values of the modified local SCORAD (primary variable) on Day 15.
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Subject analysis set title |
Placebo
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The evaluation of efficacy was performed for the valid cases set (VCS), which is equivalent to the intention-to-treat analysis set. The VCS included all randomised patients without any major protocol violation, i.e. violations that would interfere with the primary analysis, as shown below.
Major protocol violation:
• Violation of inclusion criteria;
• Application of any interfering concomitant medication;
• Application of less than 60 % or more than 145% of the full planned IMP amount (7.25 g), i.e. less than 4.35 g or more than 10.51 g, of any of the two IMPs;
• Missing values of the modified local SCORAD (primary variable) on Day 15.
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End point title |
1_Modified local SCORAD on Day 15 -- Change from baseline | ||||||||||||
End point description |
The modified local SCORAD* intensity scale represents one part of the SCORAD index, which is a severity scoring system for AD.
The intensity part includes the following local intensity criteria: erythema, edema/papulation, oozing/crusts, excoriations, and lichenification.
The intensity of each of the criteria was graded according to the 4 point scale: 0=absent; 1=mild; 2=moderate, 3=severe. The modified local SCORAD was calculated as the sum of the 5 individual scores (for the local symptoms specified above).
In this study, the severity of the lesions was assessed by the investigator at every visit.
The comparison of the IMPs was performed intra-individually.
*SCORAD=SCORing atopic dermatitis is a clinical tool for assessing the severity (i.e., extent, intensity) of AD
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End point type |
Primary
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End point timeframe |
Baseline (before treatment), Day 15.
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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Statistical analysis title |
SCORAD - Change from baseline Day 15 | ||||||||||||
Statistical analysis description |
There was no subdivision into treatment groups. The same patients were treated with both the SB011 and placebo - applying the treatment at different, prespecifies body sites - on the same day.
The total number of subjects in this analysis shown below (N=44) is not correct; this is due to a known innate error of the EudraCT database system). The correct number of patients in this analysis is N=22.
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Comparison groups |
SB011 v Placebo
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
= 0.8829 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.7 | ||||||||||||
upper limit |
0.6 | ||||||||||||
| Notes [3] - The statistical evaluation was an exploratory. |
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End point title |
2_Modified local SCORAD on Days 3, 5, 8, 12 -- Change from baseline | ||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 3, 5, 8, 12
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [4] - Valid cases set [5] - Valid cases set |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
3_Modified local SCORAD on Days 1, 3, 5, 8, 12, 15 | ||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 1, 3, 5, 8, 12, 15
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [6] - Valid cases set [7] - Valid cases set |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
4_Transepidermal water loss (TEWL) -- on Days 3, 5, 8, 12, 15 -- -- Change from baseline | |||||||||||||||||||||||||||
End point description |
Measurement of TEWL (evaporimetry) is a widely used non-invasive method for evaluation of skin impairment.
TEWL, expressed in grams per square cm and per hour, is used to study the water barrier function of the human skin. The more perfect the skin protective coat, the higher the water content and the lower the TEWL.
In this study, TEWL was measured using a Tewameter (TM 300, Courage & Khazaka, either attached to an MPA9 central unit and a PC with the appropriate software or as a stand-alone device) after acclimatisation of the patient for 30 minutes.
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 3, 5, 8, 12, 15
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [8] - Valid cases set [9] - Valid cases set |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
5_Transepidermal water loss (TEWL) -- on Days 1, 3, 5, 8, 12, 15 | ||||||||||||||||||||||||||||||
End point description |
Measurement of TEWL (evaporimetry) is a widely used non-invasive method for evaluation of skin impairment.
TEWL, expressed in grams per square cm and per hour, is used to study the water barrier function of the human skin. The more perfect the skin protective coat, the higher the water content and the lower the TEWL.
In this study, TEWL was measured using a Tewameter (TM 300, Courage & Khazaka, either attached to an MPA9 central unit and a PC with the appropriate software or as a stand-alone device) after acclimatisation of the patient for 30 minutes.
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 1, 3, 5, 8, 12, 15
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [10] - Valid cases set [11] - Valid cases set |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
6_Subjective assessment of pruritus -- on Days 1, 3, 5, 8, 12, 15 | ||||||||||||||||||||||||||||||
End point description |
Severity of pruritus (itching) during the last 24 hours was assessed in each test area by asking the patients and recording the score of a 10-point scale ranging from: “no itching” (score 1) to “worst possible itching” (score 10).
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 1, 3, 5, 8, 12, 15
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [12] - Valid cases set [13] - Valid cases set |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
7_Subjective efficacy assessment on Days 3, 5, 8, 12, 15 | |||||||||||||||||||||||||||
End point description |
Efficacy of the IMPs was assessed in each test area by asking the patients to use the following 5-point rating score scale: 0=No activity; 1=Poor; 2=Fair; 3=Good; 4=Excellent.
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End point type |
Secondary
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End point timeframe |
Baseline (before treatment), Days 3, 5, 8, 12, 15
Baseline(Day 1)=Last observation collected prior to application of first dose of study drug.
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| Notes [14] - Valid cases set [15] - Valid cases set |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were monitored throughout the study: from the time of signing the informed consent form until end of study visit or up to study discontinuation.
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Adverse event reporting additional description |
The safety evaluation set (SES) included all patients who received any IMP at least once; all safety and pharmacokinetic analyses were based on the SES.
Skin area fields, treated with the SB011 (test) and placebo, were assessed and reported separately.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.5
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Reporting groups
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Reporting group title |
SB011
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Nov 2014 |
Amendment 03 to the original clinical trial protocol was necessary because the inclusion criterion No. 3 was partly changed; Body weight according to a Body Mass Index (BMI) ≥18.0 and ≤29.0 kg/m². |
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01 Jun 2016 |
Amendment 05 was necessary because the in- and exclusion criteria were changed to facilitate recruitment; restriction by Body Mass index (BMI) was deleted.
Patients with a resting heart rate <50 and >100 bpm, systolic blood pressure <90 and >150 mmHg, diastolic blood pressure <50 and >95 mmHg, on condition that the patient does not present any clinical symptoms of hypotension.
Patients smoking ≤10 cigarettes/day. |
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30 Jun 2016 |
Amendment 07 to clinical trial protocol was necessary because the deputy investigator has changed. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
