Clinical Trial Results:
A phase IIa efficacy and safety trial with intravenous S95011 in primary Sjögren’s Syndrome patients. An international, multicentre, randomised, double-blind, placebo-controlled study
Summary
|
|
EudraCT number |
2020-001526-59 |
Trial protocol |
GB HU DE |
Global end of trial date |
02 May 2023
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
06 Mar 2024
|
First version publication date |
06 Mar 2024
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
CL2-95011-001
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04605978 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Institut de Recherches Internationales Servier (I.R.I.S.)
|
||
Sponsor organisation address |
50 rue Carnot, Suresnes Cedex, France, 92284
|
||
Public contact |
Clinical Studies Department, Institut de Recherches Internationales Servier, +33 155 72 43 66, clinicaltrials@servier.com
|
||
Scientific contact |
Clinical Studies Department, Institut de Recherches Internationales Servier, +33 155 72 43 66, clinicaltrials@servier.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
02 May 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
02 May 2023
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To assess the effect of multiple intravenous infusions of 750 mg of S95011 compared to placebo after 13 weeks of treatment in reducing disease activity using European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI)
|
||
Protection of trial subjects |
The study was conducted in accordance with the protocol and with the following: Consensus ethical principles derived from international guidelines including the Declaration of Helsinki, 1964, as revised in Fortaleza, 2013; Applicable Good Clinical Practice (GCP) guidelines; Applicable laws and regulations.
The study was initiated only after the Ethics Committee's approval, in accordance with the local regulations in each of the countries.
Patients were to give freely their written informed consent (by signing the main study ICF [or screening ICF]) before the start of the screening process of the study.
|
||
Background therapy |
Those patients who were receiving permitted medications for pSS [oral corticosteroids (prednisone or equivalent), anti-malarials, methotrexate, NSAIDs, artificial tears and artificial saliva/salivary stimulants (e.g. cevimeline, pilocarpine), cyclosporine eye drops and lifitegrast], must be maintained on a stable regimen throughout the treatment period compared to baseline. These treatments are considered “usual” background therapy in the absence of recognized standard of care. | ||
Evidence for comparator |
Matching placebo | ||
Actual start date of recruitment |
03 Aug 2021
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
4 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Australia: 5
|
||
Country: Number of subjects enrolled |
United States: 2
|
||
Country: Number of subjects enrolled |
Spain: 9
|
||
Country: Number of subjects enrolled |
United Kingdom: 6
|
||
Country: Number of subjects enrolled |
France: 5
|
||
Country: Number of subjects enrolled |
Germany: 8
|
||
Country: Number of subjects enrolled |
Hungary: 13
|
||
Worldwide total number of subjects |
48
|
||
EEA total number of subjects |
35
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
38
|
||
From 65 to 84 years |
10
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
Overall, 19 centers in 7 countries recruited patients. | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
The target population is male or female patients suffering from primary Sjögren’s Syndrome with moderate to high activity disease level (ie, systemic manifestations): adults, male or female, diagnosed with primary Sjögren’s Syndrome (pSS based) on 2016 American College of Rheumatology-EULAR criteria who fulfilled inclusion criteria of the study. | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Treatment period (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||
Blinding implementation details |
This is a double-blind, placebo-controlled study.
The appearance and form of S95011 vials and placebo vials as well as the solutions to be administered were similar, in order to protect the blinding with regard to the patients and the investigators. Patients were randomised to S95011 or placebo in an overall 2:1 ratio by Interactive Web Response
System (IWRS).
|
||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
Experimental S95011 | ||||||||||||||||||
Arm description |
Subjects randomized to receive S95011 concentrate for solution for infusion. S95011 is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
S95011
|
||||||||||||||||||
Investigational medicinal product code |
S95011
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||
Dosage and administration details |
S95011 - Dose: 750 mg (2 mL extractable volume vials containing 100 mg of S95011 (50 mg/mL) concentrate for solution for intravenous administration). The administration schedule is one IV infusion every 2 weeks (Q2W) for the first month (W000, W002, W004) and then every 3 weeks (Q3W) until W010 (W007, W010).
|
||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||
Arm description |
Subjects randomized to receive matching placebo concentrate for solution for infusion. Placebo is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||
Dosage and administration details |
2 mL extractable volume matching vials containing concentrate for solution for intravenous administration. The administration schedule is one IV infusion Q2W for the first month (W000, W002, W004) and then Q3W until W010 (W007, W010).
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Experimental S95011
|
||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomized to receive S95011 concentrate for solution for infusion. S95011 is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomized to receive matching placebo concentrate for solution for infusion. Placebo is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | ||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Experimental S95011
|
||
Reporting group description |
Subjects randomized to receive S95011 concentrate for solution for infusion. S95011 is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Subjects randomized to receive matching placebo concentrate for solution for infusion. Placebo is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. |
|
||||||||||||||||
End point title |
Change in ESSDAI Total Score from baseline to W013 | |||||||||||||||
End point description |
Efficacy criterion Eular Sjögren Syndrome Disease Activity index (ESSDAI) is a physician-administered clinical index which has been validated to objectively assess systemic manifestations in Primary Sjögren’s Syndrome patients. Scores range from 0 - 123, with a lower score representing less disease activity. Among 48 patients in the Randomized Set (RS), at least one Intercurrent event (IE) occurred for 5 patients in the S95011 group and 4 in the placebo group. Change in ESSDAI Total Score is computed only on observed values before occurrence of Intercurrent Events, therefore some participant data is missing.
Note: Due to the presence of missing data or intercurrent events before W013, the change from baseline to W013 was computed only on observed values, i.e.: 26 and 13 subjects respectively in S95011 and placebo groups.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From baseline to W013
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Statistical Analysis: Change in ESSDAI Total Score | |||||||||||||||
Statistical analysis description |
General Linear Model
This analysis was performed on all patients after imputation of missing data following several imputation strategies depending on the reason for missingness (already missing or set as missing post intercurrent event).
|
|||||||||||||||
Comparison groups |
Experimental S95011 v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
48
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.942 | |||||||||||||||
Method |
General Linear Model | |||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||
Point estimate |
2.44
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
-0.61 | |||||||||||||||
upper limit |
5.49 | |||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||
Dispersion value |
1.55
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Overall study period from Selection visit to W028.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All patients who had taken at least one dose of IMP are included in the Safety Set.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Experimental S95011
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomized to receive S95011 concentrate for solution for infusion. S95011 is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomized to receive matching concentrate for solution for infusion. Placebo is administered by one IV infusion every 2 weeks for the first month and then every 3 weeks until W010. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Oct 2020 |
Amendment No. 1:
• Implementation of a DSMB who would review the safety data and give recommendations regarding the conduct of the study. Removal of the stopping rules for premature discontinuation and temporary halt, since DSMB recommendations were to be followed instead
• Addition of ECG at W010
• Extension of the screening period to 4 weeks
• Addition of instructions on premature discontinuation of the study in an investigator site (early site closure)
• Modification of the exclusion criteria concerning prior administration of rituximab or other B cell depleting agents eg, VAY736
• Modification of exclusion criterion No. 31 (ongoing medication)
• Addition of a paragraph about rescue treatment
• Modification of the AEs list leading to premature discontinuation of the IMP
• Specification that adjustments and/or interruptions of IMP were not allowed in the study
• Modification of the reporting rules regarding the symptoms related to pSS
|
||
24 Mar 2022 |
Amendment No. 2:
• Update to the exclusion criteria No. 30 to allow rituximab or other B cell depleting agents if the CD19 B cell count was within normal range at randomization (W000) and to specify that prior administration of JAK inhibitors was forbidden
• Update of exclusion criterion No. 17 (in case of participation in another clinical study)
• Update of exclusion criterion No. 31 adding medications known to cause dry mouth/eyes
• Update of the oversight of a physician on safety data collected on e-CRF
|
||
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 |