Clinical Trial Results:
SATURN: A phase II exploration of the dynamic interaction between IL-17, IL-17 inhibition with (secukinumab) and neutrophils in psoriatic arthritis in vitro and ex vivo with exploratory study on the potential role of Vitamin D
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Summary
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EudraCT number |
2015-004502-42 |
Trial protocol |
GB |
Global end of trial date |
19 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Mar 2020
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First version publication date |
27 Mar 2020
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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 |
UoL001145
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Additional study identifiers
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ISRCTN number |
ISRCTN16488621 | ||
US NCT number |
NCT02854163 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Liverpool
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Sponsor organisation address |
2nd Floor, Block D, Waterhouse Building 3 Brownlow Street, Liverpool, United Kingdom, L69 3GL
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Public contact |
Trial Co-ordinator, Liverpool Cancer Trials Unit, +44 1517957323, diane.carlton@liverpool.ac.uk
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Scientific contact |
Trial Co-ordinator, Liverpool Cancer Trials Unit, +44 1517957323, diane.carlton@liverpool.ac.uk
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Sponsor organisation name |
University of Liverpool/Liverpool Joint Research Office
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Sponsor organisation address |
2nd Floor Block D Waterhouse Building, 3 Brownlow St, Liverpool, Liverpool, United Kingdom, L69 3GL
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Public contact |
SATURN Trial Coordinator, LCTC
Liverpool Clinical Trials Centre (LCTC)
University of Liverpool
1st Floor Block C, W, 0151 795 7323, dcarlton@liverpool.ac.uk
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Scientific contact |
SATURN Trial Coordinator, LCTC (Stats)
Liverpool Clinical Trials Centre (LCTC)
University of Liverpool
1st Floor Block C, W, 0151 795 7323, dcarlton@liverpool.ac.uk
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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 |
10 Feb 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Mar 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Sep 2019
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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 |
We propose an open label pragmatic clinical and laboratory study designed to to determine the molecular effects of IL-17 and inhibition of IL-17 with secukinumab on neutrophil phenotype and lifespan changes over time.
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Protection of trial subjects |
Trial Steering Committee (TSC)
SATURN Trial Steering Committee is responsible for providing overall supervision of the trial. In particular, the TSC will concentrate on the progress of the trial, adherence to the protocol, patient safety and consideration of new information. The TSC must be in agreement with the final Protocol and, throughout the trial, will take responsibility for:
o Making major decisions such as continuing or terminating the trial.
o Determine whether amendments to the protocol or changes in study conduct are required.
o Monitoring and supervising the progress of the trial.
o Reviewing relevant information from external sources.
o Convening any ‘Ad Hoc’ Safety Committee (if the need arises).
o Considering recommendations from any ‘Ad Hoc’ Safety Committee (if necessary to convene).
o Advising the TMG on all aspects of the trial.
Meetings will be held at regular intervals determined by need, but no less than once a year. The ultimate decision for the continuation of the trial lies with the TSC.
A TSC Charter will be agreed at the first meeting which will detail how it will conduct business.
Ad-hoc Safety Committee
If a situation arises where a high proportion of patients Serious Adverse Event reporting, an ad-hoc safety committee will be convened to specifically look at safety. In this
situation the ‘ad-hoc’ ISDMC will provide recommendations to the Trial Steering Committee concerning the continuation of the study.
Independent Data and Safety Monitoring Committee (ISDMC)
The ISDMC will be responsible for reviewing and assessing recruitment, interim monitoring of safety and effectiveness, trial conduct and external data. The ISDMC will first convene prior to trial opening and will then define frequency of subsequent meeting (at least annually).
The ISDMC will provide a recommendation to the Trial Steering committee concerning the continuation of the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Oct 2016
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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 |
United Kingdom: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
16
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Sample Size: 20 Patients plus 10 healthy controls are to be enrolled from 1 study centre (Aintree University Hospital) Recruitment was estimated to be over a period of 24 months in total with 12 months of therapy, and 12 months for staggered enrolment and laboratory investigations. | ||||||
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Pre-assignment
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Screening details |
48 screened 19 registered to the treatment arm, 1 registered to DMARD only and 10 registered to the healthy control arm. | ||||||
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Secukinumab | ||||||
Arm description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SECUKINUMAB
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Investigational medicinal product code |
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Other name |
Cosentyx
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All doses of secukinumab will be given subcutaneously (sc) using the following schedule: Weekly injection of up to 150 – 300 mg sc injections for four week induction period, followed by injections of 150 mg once a month thereafter, for the remainder of the study period (total of 12 months).
No dose modification should be used for secukinumab.
DMARD medication
Patients will continue to use their normal DMARD treatment, with standard monitoring according to normal clinical practice for the length of the trial.
The patients will continue on their standard DMARD therapy which will consist of one of the following medications: sulphsalazine, methotrexate or leflunomide with standard monitoring according to normal clinical practice for the length of the trial.
DMARD dosing will be kept stable where possible, following standard protocols used in the clinic for normal clinical practice. Standard drug monitoring procedures will be performed (e.g., monthly blood tests for methotrexate)
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The second DMARD only arm recruited 1 patient who withdrew consent before treatment administered and therefore is not part of the analysis set. Only the 19 patients on Secukinumab were analysed |
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Period 2
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Period 2 title |
Week 12
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Is this the baseline period? |
No | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Secukinumab | ||||||
Arm description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SECUKINUMAB
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Investigational medicinal product code |
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Other name |
Cosentyx
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All doses of secukinumab will be given subcutaneously (sc) using the following schedule: Weekly injection of up to 150 – 300 mg sc injections for four week induction period, followed by injections of 150 mg once a month thereafter, for the remainder of the study period (total of 12 months).
No dose modification should be used for secukinumab.
DMARD medication
Patients will continue to use their normal DMARD treatment, with standard monitoring according to normal clinical practice for the length of the trial.
The patients will continue on their standard DMARD therapy which will consist of one of the following medications: sulphsalazine, methotrexate or leflunomide with standard monitoring according to normal clinical practice for the length of the trial.
DMARD dosing will be kept stable where possible, following standard protocols used in the clinic for normal clinical practice. Standard drug monitoring procedures will be performed (e.g., monthly blood tests for methotrexate)
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Period 3
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Period 3 title |
Week 24
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Is this the baseline period? |
No | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Secukinumab | ||||||
Arm description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SECUKINUMAB
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Investigational medicinal product code |
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Other name |
Cosentyx
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All doses of secukinumab will be given subcutaneously (sc) using the following schedule: Weekly injection of up to 150 – 300 mg sc injections for four week induction period, followed by injections of 150 mg once a month thereafter, for the remainder of the study period (total of 12 months).
No dose modification should be used for secukinumab.
DMARD medication
Patients will continue to use their normal DMARD treatment, with standard monitoring according to normal clinical practice for the length of the trial.
The patients will continue on their standard DMARD therapy which will consist of one of the following medications: sulphsalazine, methotrexate or leflunomide with standard monitoring according to normal clinical practice for the length of the trial.
DMARD dosing will be kept stable where possible, following standard protocols used in the clinic for normal clinical practice. Standard drug monitoring procedures will be performed (e.g., monthly blood tests for methotrexate)
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Period 4
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Period 4 title |
Week 36
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Is this the baseline period? |
No | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Secukinumab | ||||||
Arm description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SECUKINUMAB
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Investigational medicinal product code |
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Other name |
Cosentyx
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All doses of secukinumab will be given subcutaneously (sc) using the following schedule: Weekly injection of up to 150 – 300 mg sc injections for four week induction period, followed by injections of 150 mg once a month thereafter, for the remainder of the study period (total of 12 months).
No dose modification should be used for secukinumab.
DMARD medication
Patients will continue to use their normal DMARD treatment, with standard monitoring according to normal clinical practice for the length of the trial.
The patients will continue on their standard DMARD therapy which will consist of one of the following medications: sulphsalazine, methotrexate or leflunomide with standard monitoring according to normal clinical practice for the length of the trial.
DMARD dosing will be kept stable where possible, following standard protocols used in the clinic for normal clinical practice. Standard drug monitoring procedures will be performed (e.g., monthly blood tests for methotrexate)
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Period 5
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Period 5 title |
Week 48
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Is this the baseline period? |
No | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Secukinumab | ||||||
Arm description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SECUKINUMAB
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Investigational medicinal product code |
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Other name |
Cosentyx
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All doses of secukinumab will be given subcutaneously (sc) using the following schedule: Weekly injection of up to 150 – 300 mg sc injections for four week induction period, followed by injections of 150 mg once a month thereafter, for the remainder of the study period (total of 12 months).
No dose modification should be used for secukinumab.
DMARD medication
Patients will continue to use their normal DMARD treatment, with standard monitoring according to normal clinical practice for the length of the trial.
The patients will continue on their standard DMARD therapy which will consist of one of the following medications: sulphsalazine, methotrexate or leflunomide with standard monitoring according to normal clinical practice for the length of the trial.
DMARD dosing will be kept stable where possible, following standard protocols used in the clinic for normal clinical practice. Standard drug monitoring procedures will be performed (e.g., monthly blood tests for methotrexate)
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
In order to follow the intention to treat principle (ITT) this will consist of all registered patients except for:
a) Patients withdrawing consent between registration and starting therapy
b) Patients withdrawn from the study after registration because of irregularities
with the consent process
c) Patients whose information determining ineligibility existed before
registration but was not read until after registration.
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End points reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||
Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||
Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||
Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||
Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 150-300mg subcutaneous injection once weekly for the first 4 weeks then 150mg 4 weekly for up to 48 weeks. In addition, patients will continue receiving their normal disease modifying anti- rheumatic drugs (DMARD). | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In order to follow the intention to treat principle (ITT) this will consist of all registered patients except for:
a) Patients withdrawing consent between registration and starting therapy
b) Patients withdrawn from the study after registration because of irregularities
with the consent process
c) Patients whose information determining ineligibility existed before
registration but was not read until after registration.
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End point title |
CD16 [1] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD16
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End point type |
Primary
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End point timeframe |
Collected at baseline, week 12 , week 24 and week 48
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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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 12a |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
CD16 change from baseline [2] | ||||||||||||||||
End point description |
Change from baseline CD16 Mean Fluorescent Intensity
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End point type |
Primary
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End point timeframe |
Data collected baseline, week 12, week 24 and week 48
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| Notes [2] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 12b |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
CD64 [3] | ||||||||||||||||||||
End point description |
Longitudinal analysis of Neutrophil phenotype CD64 Mean Fluorescent Intensity over time
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End point type |
Primary
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End point timeframe |
Baseline, week 12, week 24 and week 48
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| Notes [3] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 13a |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
CD64 change from baseline [4] | ||||||||||||||||
End point description |
Change from baseline CD64 Mean Fluorescent Intensity
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End point type |
Primary
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End point timeframe |
Baseline, week 12, week 24 and week 48
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| Notes [4] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 13b |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
CD11b [5] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD11b
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End point type |
Primary
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End point timeframe |
baseline, week 12, week 24 and week 48
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| Notes [5] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 14a |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
CD11b change from baseline [6] | ||||||||||||||||
End point description |
Change from baseline CD11b Mean Fluorescent Intensity
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End point type |
Primary
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End point timeframe |
Baseline, week 12, week 24 and week 48
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| Notes [6] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 14b |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
CD18 [7] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD18
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End point type |
Primary
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End point timeframe |
baseline, week 12, week 24 and week 48
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| Notes [7] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
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Attachments |
Table 15a |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
CD18 change from baseline [8] | ||||||||||||||||
End point description |
Change from baseline CD18 Mean Fluorescent Intensity
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End point type |
Primary
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End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||
| Notes [8] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||
|
|||||||||||||||||
Attachments |
Table 15b |
||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||
End point title |
CD62L [9] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD62L
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [9] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 16a |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
CD62L change from baseline [10] | ||||||||||||||||
End point description |
Change from baseline CD62L Mean Fluorescent Intensity
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||
| Notes [10] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||
|
|||||||||||||||||
Attachments |
Table 16b |
||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||
End point title |
CD63 [11] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD63
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [11] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 17a |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
CD63 change from baseline [12] | ||||||||||||||||
End point description |
Change from baseline CD63 Mean Fluorescent Intensity
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||
| Notes [12] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||
|
|||||||||||||||||
Attachments |
Table 17b |
||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||
End point title |
CD66b [13] | ||||||||||||||||||||
End point description |
Mean Fluorescent Intensity of Neutrophil receptor CD66b
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [13] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 18a |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
CD66b change from baseline [14] | ||||||||||||||||
End point description |
Change from baseline CD66b Mean Fluorescent Intensity
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||
| Notes [14] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||
|
|||||||||||||||||
Attachments |
Table 18b |
||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||
End point title |
Neutrophil lifespan (% apoptosis) [15] | ||||||||||||||||||||
End point description |
Neutrophil lifespan (% apoptosis)
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [15] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 20 |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Neutrophil lifespan (% apoptosis) with added cytokine GMCSF [16] | ||||||||||||||||||||
End point description |
Neutrophil lifespan (% apoptosis) with added cytokine GMCSF
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [16] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 21 |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Neutrophil lifespan (% apoptosis) with added cytokine TNF [17] | ||||||||||||||||||||
End point description |
Neutrophil lifespan (% apoptosis) with added cytokine TNF
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
| Notes [17] - 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: Endpoint was analysed using a longitudinal model, the resulting Least squares means (95% CI) and estimates are provided at each time point. As 1 arm study there was no comparison only change from baseline. Please see attached tables for each result for more details |
|||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 22 |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Vitamin D Receptor (neutrophil) | ||||||||||||||||||||
End point description |
Vitamin D Receptor (neutrophil)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
baseline, week, week 24 and week 48
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 23 |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Vitamin D Receptor (Other) | ||||||||||||||||||||
End point description |
Vitamin D Receptor (Other)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24 and week 48
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Table 24 |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Vitamin D Concentration | ||||||||||||||||||||||||
End point description |
Vitamin D Concentration
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
baseline, week 12, week 24, week 36 and week 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Attachments |
Table 25 |
||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||
End point title |
Correlation between vitamin D concentration/ vitamin D receptor and neutrophil phenotype | ||||||
End point description |
correlation plots attached
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
baseline, week 12, week 24 and week 48 + week 36 for vitamin D concentrations
|
||||||
|
|||||||
Attachments |
Figure 16a-19d |
||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Clinical Response | ||||||
End point description |
exploratory endpoints looking at improvement in ACR20, PsARC, PASI75, PASI 90 from baseline over time and also longitudinal model of NAPSI overtime.
|
||||||
End point type |
Other pre-specified
|
||||||
End point timeframe |
baseline, week 12, week 24, week 36 and week 48
|
||||||
|
|||||||
Attachments |
Table 26-30 |
||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Quality of life | ||||||
End point description |
Exploratory outcome of EQ5D and HAQ scores change over time.
|
||||||
End point type |
Other pre-specified
|
||||||
End point timeframe |
Baseline, week 12, week 24, week 36 and week 48
|
||||||
|
|||||||
Attachments |
Table 31-32 |
||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
All adverse events should be reported from the point of consent until 8 weeks post the last dose of treatment.
|
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Adverse event reporting additional description |
Adverse event reporting additional description:
New non-serious adverse events begin at initiation of IMP treatment whether expected or not and should be recorded & updated at each visit.
Each event should be recorded as a separate entry AE.
Severity/grade changes should be treated as new events. Patients will be followed up until resolution.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14
|
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Reporting groups
|
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Reporting group title |
Overall
|
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Reporting group description |
Overall | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
05 Apr 2016 |
Substantial Amendment 1 (prior to greenlight) – protocol v3.0, 25th February 2016: protocol and PIS amended following MHRA review. Summary of changes:
o Additional detail on the requirement for participants of child bearing potential or male participants with partners of child bearing potential to use effective contraception for the duration of the trial and outlining the length of time following completion of the medication that participant would need wait prior to planning pregnancy.
o Addition of monthly pregnancy tests extra to the initial one performed at screening
o Modification of the tuberculosis assessment and addition of the tests to screening
o Clarification of the complete physical examination performed at screening and subsequent trial visits to add major organ systems and lymphadenopathy
o Addition of the vital signs checks (Heart Rate, Blood Pressure, Body Temperature) at screening and subsequent trial visits to comply with leflunomide SmPC
o Live vaccines was added to the list of exclusion criteria
o Addition of a final follow-up one month after the last treatment dose.
The PIS was also amended (Patient PIS version 3.0 dated 16th March 2016) to incorporate the requirement for pregnancy tests and for effective contraception for sexually active participants.
|
||
24 Mar 2017 |
Substantial Amendment 2: the following documents were updated:
o Protocol v4.0 (9th December 2016) (see amendment details below)
o Patient-PIS v4.0 (5th December 2016) to reflect the change in registration process
o Health control-PSI v3.0 dated 9th December 2016 to reflect change in registration process
o GP letter v3.0 (9th December 2016) to reflect the change in registration process
Protocol amendment summary:
• Simplification of the inclusion/exclusion criteria
• Inclusion of patients who failed at least on DMARD treatment instead of two
• Removal of the exclusion of patients taking high-potency opioid analgesic (e.g. methadone, hydromorphone, morphine)
• Patient-PIS v4.0 (5th December 2016) to reflect the change in registration process
• Healthy control-PSI v3.0 dated 9th December 2016 to reflect the change in registration process
• GP letter v3.0 (9th December 2016) to reflect the change in registration process
• Replacement of the randomisation process by a simple registration for Secukinumab, to be compared to non-study patients receiving DMARD alone. For the stud primary outcome randomisation was not required. Patients who prefer to stay on oral medication rather than a parenteral drug, or who do not like the thought of having a novel biologic, will be recruited outside of the SATURN trial as part of another research study for which the chief investigator has ethical approval to perform neutrophil measurements.
|
||
18 Jun 2018 |
Substantial Amendment 3
• SmPC – Update to section 4.8 Secukinumab change 1 - 05/04/2017
• SmPC – Update to section 4.8 Secukinumab change 2 –25/07/2017
• SmPC – Update to section 4.8 Secukinumab change 3 - 01/09/2017
• Reference Safety Information version 3
|
||
14 Jan 2019 |
Substantial Amendment 4
• Protocol summary: main inclusion criteria: change “at least two standard DMARD, and” to “at least one standard DMARD.
• Protocol summary: Study design and Analysis plan, phase 1 and phase 2: assessment time should be in weeks instead of months
• Protocol: through-out the protocol assessment time should be in weeks instead of months
• SAE section: remove the possibility for site to use the online LCTU PV system. Sites are to use paper SAE and AE form, TC will enter information on LCTU PV system.
• Oversight Committees: change to reflect the fact that SATURN has a joint TSC/ISDMC in section 16 and 17.
• Updated Blood Samples Patient Group (8.5.1) as it was not consistent with the Schedule of trial Procedures (8.1).
• Updated new Personnel – Trial Statistician and Trial Coordinator
• ISRCTN number on first page updated
• Exclusion criteria: correct numbering
• Patient Information Sheet
• Informed Consent Form
• Patient Information Sheet Re Consent
• Patient treatment diary (version 1 dated 10/05/2016)
|
||
03 Sep 2019 |
Substantial Amendment 8
• The purpose of amendment 8 was to clarify the ‘End Points of the Trial’.
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
