Clinical Trial Results:
A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Safety of REGN668 Administered Concomitantly with Topical Corticosteroids to Patients with Moderate-to-severe Atopic Dermatitis
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Summary
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EudraCT number |
2012-000946-37 |
Trial protocol |
HU DE |
Global end of trial date |
19 Dec 2012
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Results information
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Results version number |
v2(current) |
This version publication date |
18 Dec 2019
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First version publication date |
09 May 2017
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Other versions |
v1 |
Version creation reason |
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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 |
R668-AD-1121
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01639040 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Regeneron Pharmaceuticals, Inc.
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Sponsor organisation address |
777 Old Saw Mill River Rd, Tarrytown, United States, 10591
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Public contact |
Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
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Scientific contact |
Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.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 |
30 Jan 2013
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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 |
19 Dec 2012
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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 primary objective of the study was to assess the safety of repeated subcutaneous doses of Dupilumab (REGN668/SAR231893) administered concomitantly with topical corticosteroids (TCS) in adult subjects with moderate-to-severe atopic dermatitis (AD).
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
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Background therapy |
All subjects received concomitant, open-label, daily treatment for up to 28 days with Class 3 or 4 midpotency a topical corticosteroid (TCS) such as methylprednisolone aceponate 0.1%, mometasone furoate 0.1%, or betamethasone valerate 0.1%. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Jul 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 15
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Poland: 13
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Worldwide total number of subjects |
31
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EEA total number of subjects |
31
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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) |
30
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 38 subjects were screened in the study between 30 July 2012 and 20 December 2012. | |||||||||||||||
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Pre-assignment
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Screening details |
Out of 38 subjects, 31 were randomized and treated in the study. Subjects were randomized in 2:1 ratio to receive Dupilumab 300 mg or Placebo. | |||||||||||||||
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Period 1
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Period 1 title |
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, Assessor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo QW | |||||||||||||||
Arm description |
Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo (for Dupilumab)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Single subcutaneous injection in the abdomen or thigh.
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Arm title
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Dupilumab 300 mg QW | |||||||||||||||
Arm description |
Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Dupilumab
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Investigational medicinal product code |
REGN668/SAR231893
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Other name |
Dupixent
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Single subcutaneous injection in the abdomen or thigh.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo QW
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Reporting group description |
Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dupilumab 300 mg QW
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Reporting group description |
Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo QW
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Reporting group description |
Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days | ||
Reporting group title |
Dupilumab 300 mg QW
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Reporting group description |
Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days | ||
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End point title |
Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) [1] | ||||||||||||||||||||||||
End point description |
Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (from start of administration of first dose of study drug to the end of study [up to Day 78]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included subjects with both serious and non-serious AEs. Safety population included all randomized subjects who received any study drug, based on treatment received.
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End point type |
Primary
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End point timeframe |
Baseline up to the end of study (up to Day 78)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Score: Reduction of ≥50 at Day 29 - Censored Last Observation Carried Forward (LOCF) | ||||||||||||
End point description |
The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Efficacy data were set to missing after prohibited medication was used or after subject was discontinued from the study. All missing values were imputed by simple LOCF. Full analysis set (FAS) included all randomized subjects received at least 1 dose of study drug and had at least 1 post-baseline assessment, based on the treatment allocated (as randomized).
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End point type |
Other pre-specified
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End point timeframe |
Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change in Pruritus Numerical Rating Scale (NRS) From Day 1 (Baseline) to Day 29 (Week 4) | ||||||||||||
End point description |
Pruritus NRS was an assessment tool that was used to report the intensity of subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 – 10 [0 = no itch; 10 = worst itch imaginable]). FAS included all randomized subjects received at least 1 dose of study drug and had at least 1 post-baseline assessment, based on the treatment allocated (as randomized).
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Achieving an Investigator’s Global Assessment (IGA) Score of "0" or "1" at Day 29 | ||||||||||||
End point description |
IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). FAS included all randomized subjects received at least 1 dose of study drug and had at least 1 post-baseline assessment, based on the treatment allocated (as randomized).
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End point type |
Other pre-specified
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End point timeframe |
Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change in Investigator’s Global Assessment (IGA) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF | ||||||||||||
End point description |
IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to missing after prohibited medication was used or after the subject was discontinued from the study. Then, all missing values were imputed by simple LOCF. FAS included all randomized subjects received at least 1 dose of study drug and had at least 1 post-baseline assessment, based on the treatment allocated (as randomized).
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change in Eczema Area and Severity Index (EASI) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF | ||||||||||||
End point description |
EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Efficacy data were set to missing after prohibited medication was used or after subject was discontinued from study. All missing values were imputed by simple LOCF. FAS included all randomized subjects received at least 1 dose of study drug and had at least 1 post-baseline assessment, based on the treatment allocated (as randomized).
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 29
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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 |
All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that are AEs that developed/worsened during the ‘on treatment period’ (day from first dose of study drug to the end of study visit [up to Day 78]).
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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 |
15.0
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Reporting groups
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Reporting group title |
Dupilumab 300 mg QW
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Reporting group description |
Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo QW
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Reporting group description |
Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Apr 2012 |
The purpose of the amendment was to indicate that collection of RNA samples (part of the research samples collected during the study) could have required separate informed consent, as required by local regulatory authorities. |
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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. | |||
| This was a small safety study that was not adequately powered to assess efficacy. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/25006719 |
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