Clinical Trial Results:
A double-blind, randomized, vehicle-controlled clinical multi-center study to evaluate the efficacy and safety of N-Acetyl-GED-0507-34-LEVO gel, 2 and 5%, applied once daily for 12 weeks in patients with facial acne vulgaris
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Summary
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EudraCT number |
2018-003307-19 |
Trial protocol |
DE PL IT |
Global end of trial date |
13 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Jun 2022
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First version publication date |
10 Jun 2022
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Other versions |
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Summary report(s) |
GEDACNE - Summary final version_05.10.2020_signed |
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 |
NAC-GED-0507-ACN-01-18
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
PPM SERVICES SA
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Sponsor organisation address |
Viale Serfontana 10, Morbio Inferiore, Switzerland, 6834
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Public contact |
DR. SALVATORE BELLINVIA, PPM SERVICES SA, 0041 916969710, gedacne_globalpm@ppmservices.ch
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Scientific contact |
DR. SALVATORE BELLINVIA, PPM SERVICES SA, 0041 916969710, gedacne_globalpm@ppmservices.ch
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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 |
05 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
13 May 2020
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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 |
The objective of the study is to evaluate the efficacy and the local and systemic safety of 2% and 5% N-Acetyl-GED-0507-34-Levo gel, in comparison to the corresponding vehicle gel, applied once daily (OD) for 12 weeks in patients with facial acne vulgaris
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Protection of trial subjects |
The protocol version 1.2 of 28 January 2019 (Italy CA requirements added) was submitted both to the Italian and Polish Regulatory Agency and relative CECs and received a favourable opinion on 26 February 2019 (Italian CEC) and on 14 February 2019 (Polish CEC) and the authorization from Italian CA on 07 February 2019 and from Polish CA on 09May 2019. The protocol version 1.3 of 13 May 2019 (German CA requirements added) was submitted both to the German Regulatory Agency (BfArM) and relative CEC and received a favourable opinion on 27 June 2019 (German CA) and on 12 July 2019 (German CEC). This clinical trial was conducted in Italy, Poland and German under the supervision of the following national coordinators:
Prof. Mauro Picardo - Italy coordinator
Prof Christos C. Zouboulis – Germany coordinator
Prof. Adam Reich – Poland coordinator
The study protocol (no. NAC-GED-0507-ACN-01-18 Eudract Number: 2018-003307-19) was conducted in compliance with specific regulatory requirements of the involved countries’ requirements This trial was conducted in compliance with the most recent version of the Declaration of Helsinki (Fortaleza, Brazil, October 2013), the most recent version of the Good Clinical Practice (GCP), and all applicable regulatory requirements (European Directive 2001/20/EC, 04 April 2001), and Italian Laws (D.lgs no. 211, 24 June 2003 and all applicable regulations).
The Study has been strongly affected by the COVID19 pandemic. All the COVID19 guidelines released by EMA and local Competent Authorities have been applied. On 22th March 2020 a contingency plan has been released by PPM Services and notified to all the involved CA and Ethics Committees accordingly to the local procedures.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
29 Mar 2019
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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 |
Poland: 235
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Country: Number of subjects enrolled |
Germany: 46
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Country: Number of subjects enrolled |
Italy: 169
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Worldwide total number of subjects |
450
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EEA total number of subjects |
450
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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) |
263
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Adults (18-64 years) |
187
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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 |
Date of first enrolment: 29 March 2019 (first randomized patient) Date of last completed: 13 May 2020 (last visit of the last patient) | ||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 450 patients have been recruited in the study: • 150 Patients were randomized to NAC-GED 5% • 150 Patients were randomized to NAC-GED 2% • 150 Patients were randomized to vehicle | ||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (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 treatment group designation remained blinded to the sites until the final database was locked.
Randomization was supported by the interactive web response system (IWRS) to ensure study medication assignment according to stratification.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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IMP 5% | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
N-ACETYL-GED-0507-34-LEVO gel 5% | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
N-Acetyl-GED-0507-34- Levo 5% gel
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Investigational medicinal product code |
N-Acetyl-GED-0507-34- Levo 5% gel
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
N-ACETYL-GED-0507-34-LEVO GEL 5% daily application for 12 weeks
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Arm title
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IMP 2% | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
N-ACETYL-GED-0507-34-LEVO GEL 2% | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
N-Acetyl-GED-0507-34- Levo 2% gel
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Investigational medicinal product code |
N-Acetyl-GED-0507-34- Levo 2% gel
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
N-ACETYL-GED-0507-34-LEVO GEL 2% daily application for 12 weeks
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Arm title
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PLACEBO | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
PLACEBO | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Vehicle | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
ITT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IMP 5%
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Reporting group description |
N-ACETYL-GED-0507-34-LEVO gel 5% | ||
Reporting group title |
IMP 2%
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Reporting group description |
N-ACETYL-GED-0507-34-LEVO GEL 2% | ||
Reporting group title |
PLACEBO
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Reporting group description |
PLACEBO | ||
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End point title |
Efficacy IGA score (Endpoint E2) | ||||||||||||||||||||
End point description |
Proportion of patients with an IGA success defined as score of “clear” (score = 0) or “almost clear” (score = 1) and at least a 2-score point reduction in IGA at V6/Wk12. Both GED 2% and GED 5% demonstrated a high statistically significant superiority over vehicle, both in the ITT set and in the PP set.
For the IGA success rate (portion vs baseline of lesions classified “clear” or “almost clear”) with GED 2% and GED 5% being better than vehicle in the ITT set with 9.3% (p=0.0749) and 21.3% (p=0.0001), respectively. GED 2% and GED 5% were better than vehicle in the PP set with 11.4% (p=0.0277) and 33.4% (p<0.0001), respectively.
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End point type |
Primary
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End point timeframe |
week 12
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Statistical analysis title |
Primary endpoints | ||||||||||||||||||||
Statistical analysis description |
All statistical processing was performed using SAS®. Continuous variables were described by descriptive statistics (n, mean, standard deviation, Q1 and Q3, minimum, median and maximum). In the evaluation of both endpoints, the analysis was focused on the comparison between the active treatment and the control. The analysis of efficacy was conducted on the ITT and PP sets, with the ITT considered as the primary set for statistical analysis.
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Comparison groups |
IMP 5% v IMP 2% v PLACEBO
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Number of subjects included in analysis |
450
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Confidence interval |
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| Notes [1] - Frequency counts and percentages of subjects within each category were provided for categorical data. Summaries were provided for each treatment group. Hypothesis tests on the primary endpoints were conducted in the following hierarchical order: E1 and then E2 only if success on endpoint E1 was achieved. In the evaluation of both endpoints, the analysis was focused on the comparison between the active treatment and the control. |
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End point title |
Efficacy Total lesion count (Endpoint E1) | ||||||||||||||||||||
End point description |
Percent change from baseline in total lesion count (inflammatory plus non-inflammatory) at V6/Wk12.
Regarding the percent change at final visit vs baseline of the total lesion count, both GED 2% and GED 5% demonstrated a high statistically significant superiority over vehicle, both in the ITT set and in the PP set.
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End point type |
Primary
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End point timeframe |
W12
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Statistical analysis title |
Primary endpoints | ||||||||||||||||||||
Comparison groups |
IMP 5% v IMP 2% v PLACEBO
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Number of subjects included in analysis |
450
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Overall
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Adverse event reporting additional description |
Recording of treatment-emergent adverse events (TEAES) throughout the study; with special attention to local TEAEs in the treated facial area (local dermal safety*), and systemic (throughout the study)
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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 |
24
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Reporting groups
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Reporting group title |
Overall
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Reporting group description |
The most frequent TEAEs in the study were: nasopharyngitis (26), headache (9), followed by oropharyngeal pain (6) and upper respiratory tract infection (6). Also regarding topical signs and symptoms, the results are unchanged compared to the total adverse events discussed above (all the reported AEs were TEAEs). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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05 May 2020 |
The following Substantial Amendments were issued and competent EC/CAs notified:
- Substantial Amendment 01 (SA01) – submitted in Italy and Poland, to reach a standardized and objective definition of measuring acne in line with the standard normal practice. This amendment introduces different wording for the definition of the severity grades to avoid numerical ranges of lesions in grading, there are no substantial differences from a clinical point of view.
- Substantial Amendment 02 (SA02) - submitted in Germany, with the same aim of SA01.
- Substantial Amendment 03 (SA03) - submitted in Germany, to include also minor patients (aged ≥ 14 to ≤ 30 years old instead of patients aged ≥ 18 to ≤ 30 years old).
- Substantial Amendment 04 (SA04) - submitted in Germany, to add specific EC requirements.
- Substantial Amendment 05 (SA05) - submitted in Germany, to include COVID-19 related procedures (BfArm requirement).
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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. | |||
| Treatment was limited to 12 weeks and therefore longer-term data on safety&tolerability are NA. Currently available data do not allow to validate the hypothesis that prolongation of therapy beyond 12W leads to a strengthening of therapeutic effect. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/35553043 |
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