Clinical Trial Results:
A randomized, double-blind, placebo-controlled, parallel-group study of the safety, tolerability, pharmacokinetics, and therapeutic efficacy of SAR441344 in adult patients with primary Sjögren’s syndrome (pSjS)
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Summary
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EudraCT number |
2020-000511-77 |
Trial protocol |
DE BE HU |
Global end of trial date |
09 Feb 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Feb 2025
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First version publication date |
21 Feb 2025
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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 |
ACT16618
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04572841 | ||
WHO universal trial number (UTN) |
U1111-1244-2266 | ||
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Sponsors
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Sponsor organisation name |
Sanofi Aventis Recherche & Développement
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Sponsor organisation address |
82 Avenue Raspail, Gentilly, France, 94250
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Public contact |
Trial Transparency Team, Sanofi Aventis Recherche & Développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Développement, Contact-US@sanofi.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 |
04 Apr 2024
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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 |
09 Feb 2024
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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 |
To evaluate the therapeutic efficacy of 1 dose level of SAR441344 versus placebo over 12 weeks in adult participants with primary Sjögren’s syndrome (pSjS), assessed by the change of the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI).
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Protection of trial subjects |
Participants were fully informed of all pertinent aspects of clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trial, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency.
Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Nov 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 |
Argentina: 9
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Chile: 17
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Korea, Republic of: 6
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Country: Number of subjects enrolled |
Mexico: 16
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Taiwan: 3
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Country: Number of subjects enrolled |
United States: 6
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Worldwide total number of subjects |
84
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EEA total number of subjects |
26
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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) |
76
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From 65 to 84 years |
8
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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 35 centers in 12 countries. A total of 234 participants were screened from 12 November 2020 to 10 August 2023, of which 150 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria. | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 84 participants were randomized in a ratio of 1:1 to either placebo or SAR441344 (frexalimab) arm. Randomization was stratified by Baseline EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score greater than or equal to (≥) 5 versus less than (<) 5. | ||||||||||||||||||
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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, Carer, Assessor | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
Participants received a single intravenous (IV) loading dose of placebo matched to SAR441344 on Day 1, followed by a subcutaneous (SC) dose of placebo matched to SAR441344 administered once every 2 weeks (q2w) at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||
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 |
Solution for injection
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
Placebo matched to SAR441344 was administered via IV infusion on Day 1, followed by an SC injection administered q2w at Weeks 2, 4, 6, 8 and 10.
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Arm title
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SAR441344 | ||||||||||||||||||
Arm description |
Participants received a single IV loading dose of SAR441344 1200 milligram (mg) on Day 1, followed by an SC dose of SAR441344 600 mg administered q2w at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
SAR441344
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Investigational medicinal product code |
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Other name |
Frexalimab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
SAR441344 1200 mg was administered via IV infusion on Day 1, followed by an SC injection of SAR441344 600 mg administered q2w at Weeks 2, 4, 6, 8 and 10.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received a single intravenous (IV) loading dose of placebo matched to SAR441344 on Day 1, followed by a subcutaneous (SC) dose of placebo matched to SAR441344 administered once every 2 weeks (q2w) at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SAR441344
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Reporting group description |
Participants received a single IV loading dose of SAR441344 1200 milligram (mg) on Day 1, followed by an SC dose of SAR441344 600 mg administered q2w at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received a single intravenous (IV) loading dose of placebo matched to SAR441344 on Day 1, followed by a subcutaneous (SC) dose of placebo matched to SAR441344 administered once every 2 weeks (q2w) at Weeks 2, 4, 6, 8 and 10. | ||
Reporting group title |
SAR441344
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Reporting group description |
Participants received a single IV loading dose of SAR441344 1200 milligram (mg) on Day 1, followed by an SC dose of SAR441344 600 mg administered q2w at Weeks 2, 4, 6, 8 and 10. | ||
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End point title |
Change From Baseline to Week 12 in ESSDAI Score | ||||||||||||
End point description |
ESSDAI:validated,established outcome measurement for therapeutic efficacy in Sjögren’s syndrome evaluating disease activity on extra-glandular manifestations.Score includes 12 organ-specific domains(constitutional,lymphadenopathy,glandular,articular,cutaneous,pulmonary,renal,muscular,peripheral and central nervous system,hematological,biological), scored based on organ-specific items in 3-4 severity grades(0=no to 3=high).Scores are summed up in weighted way(severity grades multiplied with weights 1-6) to summarize into total score(0-123).Higher scores=worse outcome.Negative change from baseline=improvement.Baseline=Day 1 assessment value.Efficacy population=all randomly assigned participants who received at least 1 complete dose of IMP with at least 1 post-IMP administration measurement with available Baseline assessment of ESSDAI.Least squares(LS) mean is calculated using mixed models for repeated measures (MMRM).Observed values after occurrence of intercurrent events are excluded.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) to Week 12
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Statistical analysis title |
Placebo Versus SAR441344 | ||||||||||||
Statistical analysis description |
Analysis was performed for change from baseline using a mixed model for repeated measures with visit, intervention group (SAR441344 and Placebo), and visit by intervention group interaction as fixed categorical effects, and participant specific baseline ESSDAI as continuous covariate.
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Comparison groups |
Placebo v SAR441344
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Least Square Mean Difference | ||||||||||||
Point estimate |
0.32
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.39 | ||||||||||||
upper limit |
2.02 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.85
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End point title |
Change From Baseline to Week 12 in European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI) Score | ||||||||||||
End point description |
The ESSPRI is a validated and established outcome measurement, reported by participants, which rates the key disease manifestations: fatigue, dryness, and pain, based on a numeric scale ranging from 0 to 10, where 0 is defined as no symptoms and 10 as maximum imaginable complaints. The total score is the mean score of the 3 scales and ranges from 0 to 10. Higher scores indicates worse outcome. A negative change from baseline indicates improvement. Baseline is defined as Day 1 assessment value. LS mean is calculated using MMRM. Observed values after occurrence of intercurrent events are excluded. Efficacy population includes all randomly assigned participants who actually received at least 1 complete dose of IMP with at least 1 post-IMP administration measurement, with available Baseline assessment of the ESSDAI. Only participants with data collected for this endpoint are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline to Week 12 in Multidimensional Fatigue Inventory (MFI) General Fatigue Subscale and Other Subscales Score | |||||||||||||||||||||||||||
End point description |
MFI is validated,20 item self-report instrument to evaluate fatigue by investigating subscales: general fatigue,physical fatigue,mental fatigue,reduced motivation,reduced activity. Each subscale consists of 4 items that are scored from 1 (yes, this is true) to 5 (no, this is not true) on which participants indicate how listed statements applied to their current fatigue situation. Item scores are summed to create individual subscale score (4-20).Higher score=higher degree of fatigue.Negative change from baseline=improvement.Baseline=Day 1 assessment value.LS mean is calculated using ANCOVA. Observed values after occurrence of intercurrent events are excluded.Efficacy population=all randomly assigned participants who received at least 1 complete dose of IMP with at least 1 post-IMP administration measurement, with available Baseline assessment of ESSDAI. Only participants with data collected for this endpoint are reported. n=number of participants analyzed for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Mean Plasma Concentration of SAR441344 [1] | ||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of plasma concentrations of SAR441344. Pharmacokinetic (PK) population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population. Only participants with data collected at specified timepoints are reported. Here, n= number of participants analyzed for each specified category.
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End point type |
Secondary
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End point timeframe |
At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Median Plasma Concentration of SAR441344 [2] | ||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of plasma concentrations of SAR441344. PK population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population. Only participants with data collected at specified timepoints are reported. Here, n= number of participants analyzed for each specified category.
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End point type |
Secondary
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End point timeframe |
At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Maximum Plasma Concentration (Cmax) of SAR441344 [3] | ||||||||
End point description |
Blood samples were collected at the specified timepoints for the measurement of plasma concentrations of SAR441344. Cmax was assessed by a Bayesian approach using the population PK model. PK population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population. Only participants with data collected for this outcome measure are reported.
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End point type |
Secondary
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End point timeframe |
After the last SC dose on Week 10 up to 336 hours post-dose
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Half-life (t1/2z) of SAR441344 [4] | ||||||||
End point description |
Blood samples were collected at the specified timepoints for the measurement of plasma concentrations of SAR441344. t1/2z was assessed by a Bayesian approach using the population PK model. PK population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population.
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End point type |
Secondary
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End point timeframe |
Week 10 to Week 12
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Maximum Plasma Concentration (tmax) of SAR441344 [5] | ||||||||
End point description |
Blood samples were collected at the specified timepoints for the measurement of plasma concentrations of SAR441344. tmax was assessed by a Bayesian approach using the population PK model. PK population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population. Only participants with data collected for this outcome measure are reported.
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End point type |
Secondary
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End point timeframe |
After the last SC dose on Week 10 up to 336 hours post-dose
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Curve Over the Dosing Interval (AUC0-tau) of SAR441344 [6] | ||||||||
End point description |
Blood samples were collected at the specified timepoints for the measurement of plasma concentrations of SAR441344. AUC0-tau was assessed by a Bayesian approach using the population PK model. PK population included all randomized and treated participants (safety population) with adequate PK results. Participants who received only placebo were not a part of the PK population. Only participants with data collected for this outcome measure are reported.
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End point type |
Secondary
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End point timeframe |
After the last SC dose on Week 10 up to 336 hours post-dose
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESI) | ||||||||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that occurred, worsened, or became serious during the TEAE period (time from the first IMP administration up to Week 24). Serious adverse events (SAE): Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or was a congenital anomaly/birth defect. An AESI: an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor’s product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).
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End point type |
Secondary
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End point timeframe |
From first dose of IMP (Day 1) up to end of follow-up period (Week 24)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Treatment Discontinuation and Withdrawals due to TEAEs | |||||||||||||||
End point description |
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs were AEs that occurred, worsened, or became serious during the TEAE period (time from the first IMP administration up to Week 24). Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).
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End point type |
Secondary
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End point timeframe |
From first dose of IMP (Day 1) up to end of follow-up period (Week 24)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Number of Participants With Increase in Pain Intensity Compared to Pre-dose Pain Intensity at Injection Site by Verbal Descriptor Scale (VDS) | |||||||||||||||||||||||||||||||||||||||
End point description |
For measurement of local tolerability, participants had a self-evaluation using VDS before IMP administration, after completion of IMP administration, and 2 hours post-administration. Participants were asked to report sensations at injection site and rated pain severity as following grading: 0= no pain; 1= mild pain; 2= moderate pain, 3= severe pain, 4= very severe. Positive change in VDS score indicated higher pain severity compared to pre-dose pain. Numerical change provides number of grades the pain got worse (positive change) or improved (negative change). Total number of participants with pain intensity increase (change in VDS score of greater than or equal to 1) compared to pre-dose pain intensity are reported. Safety population included all randomized participants exposed to IMP (regardless of amount of treatment administered). Only participants with data collected at specified timepoints are reported. Here, n= number of participants analyzed for each specified category.
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End point type |
Secondary
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End point timeframe |
Pre-dose (within 24 hours prior IMP dosing), post-dose (up to 15 minutes after dosing) and 2 hours post-dose at Weeks 2, 4, 6, 8 and 10
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With AEs Related to Local Tolerability Findings | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. Local tolerability at injection site was assessed following IMP injection and findings at the site of injection such as injection site erythema, injection site reaction, and injection site pain were recorded. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 10
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs | |||||||||||||||||||||||||||||||||
End point description |
PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Sitting systolic blood pressure (SSBP) less than or equal to (≤)95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg; ≥160 mmHg and increase from baseline ≥20 mmHg; Sitting diastolic blood pressure (SDBP) ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥110 mmHg and increase from baseline ≥10 mmHg; Sitting heart rate (HR) ≤50 beats per minute (bpm) and decrease from baseline ≥20 bpm, ≥120 bpm and increase from baseline ≥20 bpm; Weight ≥5% decrease from baseline, ≥5% increase from baseline. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With PCSA in Electrocardiogram | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: HR <50 bpm, <40 bpm, >90 bpm, >90 bpm and increase from baseline ≥20 bpm, >100 bpm; PR interval, aggregate >200 milliseconds (msec), >200 msec and increase from baseline ≥25%, >220 msec, >220 msec and increase from baseline ≥25%, >240 msec, >240 msec and increase from baseline ≥25%; QRS duration, aggregate >110 msec, >110 msec and increase from baseline ≥25%, >120 msec, >120 msec and increase from baseline ≥25%; QT interval, aggregate >500 msec; corrected QT (QTc) correction method unspecified (CMU) >450 msec, >480 msec, increase from baseline [30-60] msec, increase from baseline >60 msec. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered). IFB= increase from baseline.
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End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) to Week 24
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With PCSA in Hematology Parameters | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PCSA values were defined as abnormal values considered medically important by Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by Sponsor. Criteria for PCSA: Hemoglobin (Hb) ≤115 grams per liter (g/L) (Male [M]) or ≤95 g/L (Female [F]), ≥185 g/L (M) or ≥165 g/L (F), decrease from baseline ≥20 g/L; Hematocrit ≤0.37 volume per volume (v/v) (M) or ≤0.32 v/v (F), ≥0.55 v/v (M) or ≥0.5 v/v (F); Erythrocytes (red blood cells [RBC]) ≥6 x 10^12 per liter (/L); Platelets <100 x 10^9/L, ≥700 x 10^9/L; Leukocytes (white blood cells [WBC]) <3 x 10^9/L (Non-Black[NB]) or <2 x 10^9/L (Black[B]), ≥16 x 10^9/L; Neutrophils <1.5 x 10^9/L (NB) or <1 x 10^9/L (B); Lymphocytes >4 x 10^9/L, <0.5 x 10^9L; Monocytes >0.7 x 10^9/L; Basophils >0.1 x 10^9/L; Eosinophils >0.5 x 10^9/L or >upper limit of normal(ULN) (if ULN ≥0.5 x 10^9/L). Safety population included all randomized participants exposed to the IMP (regardless of amount of treatment administered).
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1) to Week 24
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With PCSA in Clinical Chemistry Parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PCSA values:abnormal values considered medically important by Sponsor,according to predefined criteria/thresholds based on literature reviews;defined by Sponsor.Criteria for PCSA:Sodium≤129 millimoles per liter(mmol/L),≥160 mmol/L;Potassium<3 mmol/L,≥5.5 mmol/L;Glucose≤3.9 mmol/L and <lower limit of normal(LLN),≥11.1 mmol/L(unfasted);≥7 mmol/L(fasted); Creatine kinase(CK)>3 ULN,>10 ULN;Creatinine≥150 micromoles/L(adults),≥30% change from baseline,≥100% change from baseline;Creatinine clearance(CG)≥60-<90 milliliters per minute(mL/min)(mild decrease in glomerular filtration rate[GFR]),≥30-<60 mL/min(moderate decrease in GFR),≥15-<30 mL/min(severe decrease in GFR),<15 mL/min(end stage renal disease),Urea nitrogen≥17 mmol/L;Alkaline phosphatase(ALP)>1.5 ULN;Alanine aminotransferase(ALT)>3 ULN; ALT>3 ULN & bilirubin>2 ULN;Aspartate aminotransferase(AST)>3 ULN;Direct bilirubin>35% bilirubin & bilirubin>1.5 ULN;Total bilirubin>1.5 ULN,>2 ULN.Analysis was performed on safety population.
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1) to Week 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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End point title |
Number of Participants With PCSA in Urinalysis Parameters | |||||||||||||||
End point description |
PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Potential of hydrogen (pH) ≤4.6 or ≥8. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).
|
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1) to Week 24
|
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|
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| No statistical analyses for this end point | ||||||||||||||||
|
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End point title |
Number of Participants With Anti-drug Antibodies (ADA) to SAR441344 [7] | ||||||||||||||||
End point description |
Serum samples were collected at the specified timepoints for the assessment of ADAs to SAR441344. Number of participants with treatment-emergent ADA defined as at least 1 treatment-induced/boosted ADA during the treatment-emergent period, i.e. from the time of the IMP administration up to the end of study visit are reported. Number of participants with positive ADA are reported. ADA population included all randomized participants treated with SAR441344 with at least 1 post-baseline ADA result (positive, negative or inconclusive). Here, n= number of participants analyzed for each specified category.
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End point type |
Secondary
|
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End point timeframe |
Baseline, Week 4, Week 8, Week 12, and Week 24
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only participants in the SAR441344 arm were analyzed in this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of IMP (Day 1) up to end of follow-up period (Week 24)
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Adverse event reporting additional description |
Analysis was performed on safety population.
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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 |
26.1
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Reporting groups
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Reporting group title |
SAR441344
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Reporting group description |
Participants received a single IV loading dose of SAR441344 1200 mg on Day 1, followed by an SC dose of SAR441344 600 mg administered q2w at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received a single IV loading dose of placebo matched to SAR441344 on Day 1, followed by an SC dose of placebo matched to SAR441344 administered q2w at Weeks 2, 4, 6, 8 and 10. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
27 Aug 2020 |
The purpose of the amendment was to have minor adjustments in the exclusion criteria E01, E11, E14, and E30 to address comments raised by the European Union participating National Competent Authorities during review of the clinical trial application, via the Voluntary Harmonisation Procedure. Clarification of minor discrepancies were also addressed, as well as minor editorial and document formatting revisions were made. |
||
28 Jul 2021 |
The purpose of the amendment was to have an adjustment in the inclusion criterion I03 and to
allow re-screening for I06 to better reflect the participant population to aid recruitment without
compromising on safety requirements. Section 9.5 (Interim analysis) was extended with an early analysis after all participants have completed their End of Treatment/Week 12 visit, to allow for internal decision making. Section 6.2 was adapted to allow destruction of vials according to local regulations and a reference to the pharmacy manual was added. Clarification of discrepancies were also addressed, as well as minor editorial and document formatting revisions were made. |
||
05 Apr 2022 |
The purpose of the amendment was to adapt inclusion/exclusion criteria I06, E17, E18, and
E22 to better account for the required characteristics of Sjögren's syndrome (ESSDAI >5 and
baseline treatment) to facilitate recruitment, without compromising safety requirements. The discontinuation due to Coronavirus Disease 2019 was adjusted. Section 9.5 (Interim analysis) was revised with an option of additional analysis. Discrepancies were also addressed, as well as minor corrections and clarifications were made. |
||
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 | |||
