Clinical Trial Results:
Exploratory study on the kinetics of psoriasis symptoms, pruritus intensity and lesional biomarkers in patients with moderate to severe plaque-type psoriasis treated with subcutaneous secukinumab (300 mg) during a 16 week open-label run-in phase followed by a 16 week randomized, double-blind, placebo-controlled withdrawal phase.
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Summary
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EudraCT number |
2014-002212-16 |
Trial protocol |
DE |
Global end of trial date |
15 Jul 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jul 2017
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First version publication date |
30 Jul 2017
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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 |
CAIN457ADE03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02362789 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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 |
15 Jul 2016
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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 |
15 Jul 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 |
The main objective of study CAIN457ADE03 was to demonstrate that secukinumab has superior efficacy compared to placebo on the pruritus intensity Visual Analogue Scale (VAS, the worst itching within a recall period of 24 hours as part of the Patient’s Global Assessment of Chronic Pruritus, PGA-CP) measured at Week 32 in patients with moderate to severe psoriasis.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Mar 2015
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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: 130
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Worldwide total number of subjects |
130
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EEA total number of subjects |
130
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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) |
121
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 146 patients were screened into the study, 130 of whom entered the open-label run-in phase. 80 patients randomized to withdrawal phase. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Open-lable run-in phase
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Arm title
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Open-label: secukinumab 300 mg s.c. | |||||||||||||||||||||
Arm description |
All patients received 300 mg secukinumab at weeks 0 (baseline) , 1, 2, 3, 4, 8, 12. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
secukinumab
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Investigational medicinal product code |
AIN457A
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
300 mg secukinumab subcutaneous (two prefilled syringes each containing 150 mg secukinumab)
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Period 2
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Period 2 title |
Randomized Withdrawal Phase
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Is this the baseline period? |
No | |||||||||||||||||||||
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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Randomized withdrawal: secukinumab 300mg s.c. | |||||||||||||||||||||
Arm description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to secukinumab 300 mg at week 16, received secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
secukinumab
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Investigational medicinal product code |
AIN457A
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
300 mg secukinumab subcutaneous (two prefilled syringes each containing 150 mg secukinumab)
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Arm title
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Randomized withdrawal: placebo | |||||||||||||||||||||
Arm description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to placebo at week 16, received matching placebo of Secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
Placebo
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
matching placebo of secukinumab 300 mg s.c. (administered as two injections of 150 mg )
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Not all patietns who completed open-label run-in phase were eligible for randomized withdrawal phase. |
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Baseline characteristics reporting groups
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Reporting group title |
Open-label: secukinumab 300 mg s.c.
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Reporting group description |
All patients received 300 mg secukinumab at weeks 0 (baseline) , 1, 2, 3, 4, 8, 12. | |||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set - Randomized withdrawal phase
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Statistical Analysis for pruritus intensity VAS (the worst itching within a recall period of 24 hours as part of the PGA -CP) measured in the FAS-R at Week 32.
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End points reporting groups
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Reporting group title |
Open-label: secukinumab 300 mg s.c.
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Reporting group description |
All patients received 300 mg secukinumab at weeks 0 (baseline) , 1, 2, 3, 4, 8, 12. | ||
Reporting group title |
Randomized withdrawal: secukinumab 300mg s.c.
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Reporting group description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to secukinumab 300 mg at week 16, received secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | ||
Reporting group title |
Randomized withdrawal: placebo
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Reporting group description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to placebo at week 16, received matching placebo of Secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | ||
Subject analysis set title |
Full Analysis Set - Randomized withdrawal phase
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Statistical Analysis for pruritus intensity VAS (the worst itching within a recall period of 24 hours as part of the PGA -CP) measured in the FAS-R at Week 32.
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End point title |
Pruritus intensity VAS | ||||||||||||
End point description |
The pruritus intensity visual analogue scales (VAS) (the worst itching within a recall period of 24 hours as part of the Patients Global Assessment of Chronic Pruritus (PGA -CP)) measured in the Full Analysis Set for the randomized withdrawal phase (FAS-R) at Week 32. Patient’s Global Assessment of Chronic Pruritus (PGA-CP) is a self-administered questionnaire with a recall period of 24 hours including one component as visual analogue scales (VAS 0-100). The patients marked on the line the point that they feel represents their perception of their pruritus. 0 (no pruritus) - 100 (most severe pruritus).
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End point type |
Primary
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End point timeframe |
32 weeks
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| Notes [1] - all patients who received at least one dose of blinded study drug during randomized withdrawal phase [2] - all patients who received at least one dose of blinded study drug during randomized withdrawal phase |
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Statistical analysis title |
Statistical Analysis of Pruritis Intensity VAS | ||||||||||||
Statistical analysis description |
The primary analysis method is covariance (ANCOVA) with factors center and treatment and with covariates PASI, body weight and VAS at baseline (=week 0). Adjusted means (LS-means) are given for the difference between treatments with a 95% confidence interval and a p-value.
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Comparison groups |
Randomized withdrawal: secukinumab 300mg s.c. v Randomized withdrawal: placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.0055 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-18.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-31.01 | ||||||||||||
upper limit |
-5.59 | ||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
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Adverse event reporting additional description |
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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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 |
19.0
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Reporting groups
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Reporting group title |
Open label: secukinumab 300 mg s.c.
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Reporting group description |
All patients received 300 mg secukinumab subcutaneously at weeks 0 (baseline) , 1, 2, 3, 4, 8, 12. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Randomized withdrawal: secukinumab 300 mg s.c.
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Reporting group description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to secukinumab 300 mg at week 16, received secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Randomized withdrawal: Placebo
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Reporting group description |
Patient who completed open-label run in phase by taking secukinumab 300 mg subcutaneous at week 0, 4, 8, 12 and achieved an extensive remission , was randomized to withdrawal phase at week 16 . Patients randomized to placebo at week 16, received matching placebo of Secukinumab 300 mg subcutaneous at weeks 16, 20, 24 and 28. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
