Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects with Prurigo Nodularis
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Summary
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EudraCT number |
2019-004293-25 |
Trial protocol |
GB SE DE HU AT DK IT PL |
Global end of trial date |
21 Feb 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Jul 2024
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First version publication date |
18 Jul 2024
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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 |
RD.06.SPR.202685
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND number: 117122 | ||
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Sponsors
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Sponsor organisation name |
Galderma S.A.
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Sponsor organisation address |
Avenue Gratta-Paille 2, Lausanne, Switzerland, 1018
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Public contact |
Clinical Trial Information Desk, CTD Coordinator Galderma R&D S.A., CTA.coordinator@galderma.com
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Scientific contact |
Clinical Trial Information Desk, CTD Coordinator Galderma R&D S.A., CTA.coordinator@galderma.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 |
11 Apr 2023
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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 |
21 Feb 2023
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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 was to assess the efficacy and safety of nemolizumab (CD14152) compared to placebo in subjects greater than or equal to (>=) 18 years of age with prurigo nodularis (PN) after a 16 week treatment period.
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Protection of trial subjects |
This clinical study was conducted in accordance with the protocol, the Declaration of Helsinki, and the International Conference on Harmonization Good Clinical Practices (ICH GCP), and in compliance with other applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Aug 2020
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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 |
Poland: 21
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Country: Number of subjects enrolled |
Sweden: 2
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Country: Number of subjects enrolled |
United Kingdom: 17
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Country: Number of subjects enrolled |
Austria: 24
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Country: Number of subjects enrolled |
Denmark: 14
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Country: Number of subjects enrolled |
Germany: 99
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Country: Number of subjects enrolled |
Hungary: 4
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Country: Number of subjects enrolled |
Italy: 31
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Country: Number of subjects enrolled |
Canada: 7
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Country: Number of subjects enrolled |
United States: 67
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Worldwide total number of subjects |
286
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EEA total number of subjects |
195
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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) |
204
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From 65 to 84 years |
82
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 77 active sites in 10 countries. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 286 subjects were randomised to receive either nemolizumab (CD14152) or placebo. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall study (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 | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Nemolizumab | ||||||||||||||||||||||||||||||
Arm description |
Subjects weighing less than (<) 90 kilogram (kg) received two subcutaneous (SC) injections of 30 milligrams (mg) nemolizumab (60 mg loading dose) at baseline then one SC injection once for every 4 weeks (Q4W). Subjects weighing greater than or equal to (>=) 90 kg received two SC injections of 30 mg nemolizumab (60 mg total) at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Nemolizumab
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Investigational medicinal product code |
CD14152
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects weighing less than < 90 kg received two SC injections of 30 mg nemolizumab (60 mg loading dose) at baseline then one SC injection Q4W. Subjects weighing >= 90 kg received two SC injections of 30 mg nemolizumab (60 mg total) at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Subjects weighing <90 kg received two SC injections of matching placebo at baseline, then one SC injection Q4W. Subjects weighing >=90 kg received two SC injections of matching placebo at baseline, then two SC injections Q4W throughout the treatment period of 16 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
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 |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects weighing < 90 kg received two SC injections of matching placebo at baseline, then one SC injection Q4W. Subjects weighing >= 90 kg received two SC injections of matching placebo at baseline,
then two SC injections Q4W throughout the treatment period of 16 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Nemolizumab
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Reporting group description |
Subjects weighing less than (<) 90 kilogram (kg) received two subcutaneous (SC) injections of 30 milligrams (mg) nemolizumab (60 mg loading dose) at baseline then one SC injection once for every 4 weeks (Q4W). Subjects weighing greater than or equal to (>=) 90 kg received two SC injections of 30 mg nemolizumab (60 mg total) at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects weighing <90 kg received two SC injections of matching placebo at baseline, then one SC injection Q4W. Subjects weighing >=90 kg received two SC injections of matching placebo at baseline, then two SC injections Q4W throughout the treatment period of 16 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nemolizumab
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Reporting group description |
Subjects weighing less than (<) 90 kilogram (kg) received two subcutaneous (SC) injections of 30 milligrams (mg) nemolizumab (60 mg loading dose) at baseline then one SC injection once for every 4 weeks (Q4W). Subjects weighing greater than or equal to (>=) 90 kg received two SC injections of 30 mg nemolizumab (60 mg total) at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects weighing <90 kg received two SC injections of matching placebo at baseline, then one SC injection Q4W. Subjects weighing >=90 kg received two SC injections of matching placebo at baseline, then two SC injections Q4W throughout the treatment period of 16 weeks. | ||
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End point title |
Number of Subjects With Improvement of Greater Than or Equal to (>=) 4 From Baseline in Weekly Average PP NRS at Week 16 | |||||||||
End point description |
The Peak Pruritus NRS is a scale that was used by the subjects to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. Weekly values are calculated as the average of 7 consecutive days of data up to the target study day (excluding) and set to missing if less than 4 days of data are available. Analysis window extension was applied to both timepoints, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are
considered as non-responders. ITT population included all randomised subjects.
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End point type |
Primary
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End point timeframe |
Baseline, Week 16
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [1] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
40.1
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
29.4 | |||||||||
upper limit |
50.8 | |||||||||
| Notes [1] - A 2-sided p-value was derived from Cochran-Mantel-Haenszel (CMH) test using the randomised stratification variables (analysis center and body weight at randomisation [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With an Investigator Global Assessment (IGA) Success at Week 16 | |||||||||
End point description |
IGA success is defined as clear (0) or almost clear (1), and a reduction from baseline of greater than or equal to 2 points at week 16. Full scale is scored from 0-4, higher score indicates more severe symptoms. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT population included all randomised subjects.
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End point type |
Primary
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End point timeframe |
Baseline, Week 16
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0025 [2] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
14.6
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
6.7 | |||||||||
upper limit |
22.6 | |||||||||
| Notes [2] - A 2-sided p-value was derived from CMH test using the randomised stratification variables (analysis center and body weight at randomisation [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With Adverse Events, Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence, new or worsening of any pre-existing condition, in a clinical study subject administered a medicinal product and which did not necessarily had to have a
causal relationship with the treatment. TEAEs: AES with an onset date on or after the start date of the IMP administration. AESIs: skin-related events (SRE) (except exacerbation and infective exacerbation of PN) or injection site reactions (ISRs) as per common terminology criteria for AEs (Grade 3: ulceration or necrosis; severe tissue damage; operative intervention indicated, Grade 4: life-threatening consequences; urgent intervention indicated, Grade 5: death ). An SAE: AE that resulted in any of the following outcomes: death; life threatening; results in persistent disability; requires in-patient hospitalisation congenital anomaly; is medically significant. Safety population included all randomised subjects who received at least 1 administration of study drug.
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End point type |
Secondary
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End point timeframe |
From Baseline up to Week 32
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects With an Improvement of >= 4 From Baseline in Weekly Average PP NRS at Week 4 | |||||||||
End point description |
The Peak Pruritus NRS is a scale that was used by the subjects to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. Weekly values are calculated as average of 7 consecutive days data up to the target study day (excluding) and set to missing, if less than 4 days data are available. Analysis window extension was applied to baseline, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT population included all randomised subjects.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [3] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
31.7
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
23 | |||||||||
upper limit |
40.4 | |||||||||
| Notes [3] - A 2-sided p-value was derived from CMH test using the randomized stratification variables (analysis center and body weight at randomization [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With PP NRS < 2 at Week 16 | |||||||||
End point description |
The Peak Pruritus NRS is a scale that was used by the subjects to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. Weekly values are calculated as average of 7 consecutive days data up to the target study day (excluding) and set to missing, if less than 4 days data are available. Analysis window extension was applied to Week 16, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT population included all randomised subjects.
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End point type |
Secondary
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End point timeframe |
Week 16
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [4] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
30.5
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
22.3 | |||||||||
upper limit |
38.7 | |||||||||
| Notes [4] - A 2-sided p-value was derived from CMH test using the randomized stratification variables (analysis center and body weight at randomization [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With an Improvement of >=4 From Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Week 16 | |||||||||
End point description |
The SD NRS is a scale to report the degree of subject sleep loss related to PN. The baseline SD NRS was determined based on the average of daily SD NRS (score ranging from 0 to 10) during the 7 days up to the treatment start (including until treatment start time). A minimum of 4 daily scores out of the 7 days up to baseline study day is required for this calculation. On a scale of 0 to 10, with 0 being ‘no sleep loss related to the symptoms of my skin disease (prurigo nodularis)’ and 10 being ‘I did not sleep at all due to the symptoms of prurigo nodularis’. Higher scores indicate worse outcome. Analysis window extension was applied to both timepoints, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT population.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [5] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
38
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
27.8 | |||||||||
upper limit |
48.2 | |||||||||
| Notes [5] - A 2-sided p-value was derived from CMH test using the randomized stratification variables (analysis center and body weight at randomization [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With an Improvement of >=4 From Baseline in SD NRS at Week 4 | |||||||||
End point description |
The SD NRS is a scale to be used by the subject to report the degree of their sleep loss related to PN. The baseline SD NRS was determined based on the average of daily SD NRS (score ranging from 0 to10) during the 7 days up to the treatment start (including until treatment start time). A minimum of 4 daily scores out of the 7 days up to baseline study day is required for this calculation. On a scale of 0 to 10, with 0 being ‘no sleep loss related to the symptoms of my skin disease (prurigo nodularis)’ and 10 being ‘I did not sleep at all due to the symptoms of prurigo nodularis’. Higher scores indicate worse outcome. Analysis window extension was applied to baseline, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/ after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [6] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
22.7
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
14.7 | |||||||||
upper limit |
30.7 | |||||||||
| Notes [6] - A 2-sided p-value was derived from CMH test using the randomized stratification variables (analysis center and body weight at randomization [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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End point title |
Number of Subjects With PP NRS < 2 at Week 4 | |||||||||
End point description |
The Peak Pruritus NRS is a scale that was used by the subjects to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. Weekly values are calculated as average of 7 consecutive days data up to the target study day (excluding) and set to missing, if less than 4 days data are available. Analysis window extension was applied to baseline, as described in the SAP. If a subject received any rescue therapy, composite variable strategy is applied, the underlying data at/after receipt of rescue therapy is set as worst possible value, and the response is derived from underlying data value. Subjects with missing results are considered as non-responders. ITT population included all randomised subjects.
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End point type |
Secondary
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End point timeframe |
Week 4
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Statistical analysis title |
Nemolizumab versus Placebo | |||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints were reported and continued when previous endpoint was statistically significant at two-sided 0.05.
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Comparison groups |
Nemolizumab v Placebo
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Number of subjects included in analysis |
286
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.0001 [7] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Strata adjusted percentage difference | |||||||||
Point estimate |
18.7
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
12.3 | |||||||||
upper limit |
25 | |||||||||
| Notes [7] - A 2-sided p-value was derived from CMH test using the randomized stratification variables (analysis center and body weight at randomization [< 90 kg, >= 90 kg]). Threshold of significance at 0.05. |
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline up to Week 32
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Adverse event reporting additional description |
Safety population included all randomised subjects who received at least 1 administration of study drug.
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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 |
25.0
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Reporting groups
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Reporting group title |
Nemolizumab
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Reporting group description |
Subjects weighing < 90 kg received two SC injections of 30 mg nemolizumab (60 mg loading dose) at baseline then one SC injection Q4W. Subjects weighing >= 90 kg received two SC injections of 30 mg nemolizumab (60 mg total) at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks. Nemolizumab: Subjects received either 30 mg or 60 mg dose of nemolizumab as SC injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects weighing < 90 kg received two SC injections of matching placebo at baseline, then one SC injection Q4W. Subjects weighing >= 90 kg received two SC injections of matching placebo at baseline, then two SC injections Q4W throughout the treatment period of 16 weeks. Placebo: Subjects received matching placebo as SC injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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25 Jun 2020 |
Following changes were made: Included Galderma R&D, LLC as sponsor; Updated sponsor signatory; Updated number of sites; Included secondary objectives; Reordered primary endpoints; Updated key secondary endpoints; Updated secondary endpoints; Updated number of subjects and randomization ratio; Updated weight cutoff for dosing; Updated duration of study; Updated IC2 PN definition; Updated IC4 (prev IC5) methods of contraception; Updated IC5 (prev IC6) women of non-childbearing potential; Updated EC2 active pruritic conditions; Updated EC7 infections; Included EC 24-27 optional biopsy sampling; Updated PD sample collection, including biopsies; Updated statistical methods; Updated AESIs to include COVID-19; Updated reasons for study drug discontinuation; Included details of study drug discontinuation due to COVID-19; Clarified self-injection; Updated hypersensitivity reaction monitoring; Included details of CYP450 substrates; Updated collection timepoints in Schedule of Assessments; Updated pregnancy test footnote in Schedule of Assessments; Included subject sleep diary endpoint details; Updated medical history of asthma screening assessment; Included guidance appendix for study conduct and subject safety during COVID-19 pandemic; Updated PAS appendix.
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22 Dec 2020 |
Following changes were made: Updated the number of study sites from 60 to 70; Clarified the methods of contraception; Clarified that females of non-childbearing potential with the absence of menstrual bleeding for 1 year before screening without any other medical reason must have had a confirmed follicle-stimulating hormone level in the postmenopausal range; Added, if PEF was < 80% of the predicted value at screening in subjects without any history of asthma or in subjects with history of asthma but with the ACT score >19, PEF testing could have been repeated once within 48 hours; Added that subjects with positive HCV antibody from previous exposure/infection did not need to be excluded if a negative PCR confirmed there was no active infection. Additionally, in the event of rescreening, serology test results performed within 6 weeks before the baseline visit, could be used to assess eligibility; Clarified excluded prior treatments; Clarified current and history of untreated or inadequately treated active or latent TB infection, and rescreening procedures; Clarified that the investigational drug exclusion period was 8 weeks or 5 half-lives of the investigational drug, whichever was longer; Clarified that rescue with oral psoralen required discontinuation of study drug; Added rationale for placebo-controlled design; Updated prohibited therapy and information on permitted non-live vaccinations (seasonal, emergency, COVID-19); Clarified management of subjects with either symptomatic or asymptomatic COVID-19; Clarified permitted rescue therapies to include systemic corticosteroids and gabapentinoids; Deleted residual error in self-injection description from the schedule of assessments footnote; Clarified PK parameters and analyses; Updated the form for PD sample recording; Corrected the error in the sample size calculation (to power at 5%); Updated guidance for management of subjects during the COVID-19 pandemic. |
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19 Nov 2021 |
Following changes were made: Added the secondary efficacy endpoint of the proportion of subjects with PP NRS improvement >= 4 from baseline and IGA success at Week 16, Week 20, and Week 24;
Updated restricted prior treatments, prohibited therapy, and ADA assay information to be harmonised with other protocols in the nemolizumab program; Specified that ADA was to be determined using validated ECLIA (not ELISA). |
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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 | |||
