Clinical Trial Results:
A Phase 2, Randomized, Placebo-Controlled, Parallel-Group, Double-Blinded, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Intravenous Efgartigimod in Adult Participants With Primary Sjögren’s Syndrome
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Summary
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EudraCT number |
2021-005911-30 |
Trial protocol |
NL BE HU |
Global end of trial date |
12 Feb 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Feb 2025
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First version publication date |
26 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 |
ARGX-113-2106
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05817669 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
argenx BV
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Sponsor organisation address |
Zwijnaarde 7, Zwijnaarde (Ghent), Belgium, 9052
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Public contact |
Regulatory, argenx, regulatory@argenx.com
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Scientific contact |
Regulatory, argenx, regulatory@argenx.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 |
08 Jan 2025
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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 |
12 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 effect of efgartigimod intravenous (IV) compared to placebo on composite of relevant endpoints for Sjögren’s syndrome (CRESS).
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Protection of trial subjects |
This study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines, including the Declaration of Helsinki, applicable ICH GCP guidelines, and applicable laws and regulations. The participant’s informed consent was documented by the dated signature of the participant (and assent, if applicable) and the dated signature of the investigator or investigator’s delegate.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 May 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Poland: 21
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Worldwide total number of subjects |
34
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EEA total number of subjects |
34
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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) |
26
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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 |
This Phase 2, double-blinded study was conducted in adult participants with primary Sjögren's disease (pSjD) at 15 investigational sites in 3 countries between 08-May-2023 and 12-Feb-2024. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 34 participants were enrolled in study. Participants were randomized in a 2:1 ratio to either receive efgartigimod or placebo for 24 weeks. At end of treatment period, eligible participants rolled over to an open-label extension (OLE) study (ARGX-113-2211 [2023-503915-14]) or remained in the study for the post-treatment follow-up period. | |||||||||||||||||||||
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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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Efgartigimod | |||||||||||||||||||||
Arm description |
Participants received efgartigimod 10 milligram per kilogram (mg/kg) once weekly via IV infusion for up to 24 weeks. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Efgartigimod
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Investigational medicinal product code |
ARGX-113
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received efgartigimod 10 mg/kg once weekly via IV infusion for up to 24 weeks.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Participants received placebo matched to efgartigimod once weekly via IV infusion for up to 24 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received placebo matched to efgartigimod once weekly via IV infusion for up to 24 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Efgartigimod
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Reporting group description |
Participants received efgartigimod 10 milligram per kilogram (mg/kg) once weekly via IV infusion for up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to efgartigimod once weekly via IV infusion for up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Efgartigimod
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Reporting group description |
Participants received efgartigimod 10 milligram per kilogram (mg/kg) once weekly via IV infusion for up to 24 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to efgartigimod once weekly via IV infusion for up to 24 weeks. | ||
Subject analysis set title |
Efgartigimod (EAS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Efficacy Analysis Set: Participants received efgartigimod 10 mg/kg once weekly via IV infusion for 24 weeks.
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Subject analysis set title |
Placebo (EAS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Efficacy Analysis Set: Participants received placebo matched to efgartigimod once weekly via IV infusion for 24 weeks.
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Subject analysis set title |
Efgartigimod (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Analysis Set: Participants received efgartigimod 10 mg/kg once weekly via IV infusion for 24 weeks.
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Subject analysis set title |
Placebo (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Analysis Set: Participants received placebo matched to efgartigimod once weekly via IV infusion for 24 weeks.
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Subject analysis set title |
Efgartigimod (PKAS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Pharmacokinetic Analysis Set: Participants received efgartigimod 10 mg/kg once weekly via IV infusion for 24 weeks.
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End point title |
Percentage of Participants Meeting Overall CRESS Response on ≥3 of 5 Items at Week 24 [1] | ||||||||||||
End point description |
A Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) responder is defined as improvements in at least 3 of the 5 items of CRESS (systemic disease activity, patient-reported symptoms, tear gland function, salivary gland function and serology. The score ranges from 0 to 9 (higher score = worse symptoms).
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End point type |
Primary
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End point timeframe |
Week 24
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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: As the endpoint was descriptive in nature, no statistical analysis was reported. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With TEAEs, AESI and SAEs | ||||||||||||||||||
End point description |
A treatment-emergent adverse event (TEAE): adverse events reported from the first dose up to and including 60 days after the final dose were considered treatment-emergent. Serious adverse event (SAE): adverse event that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or other situations. Adverse event of special interest (AESI): adverse event related to 'Infections and infestations'.
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End point type |
Secondary
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End point timeframe |
Up to 32 weeks
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Participants With MCII in ESSDAI at Week 24 | ||||||||||||
End point description |
European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) measures systemic disease activity in participants with pSjD and consists of 11 organ-specific domains and 1 biological domain that contribute to disease activity level scoring. Each domain is given a certain weight, which gives a score between 0 and 123 (higher score =worse symptoms). Minimally clinically important improvement (MCII) in ESSDAI was defined as improvement of at least 3 points in ESSDAI score at Week 24.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Low Disease Activity in ESSDAI at Week 24 | ||||||||||||
End point description |
ESSDAI measures systemic disease activity in participants with pSjD and consists of 11 organ-specific domains and 1 biological domain that contribute to disease activity level scoring. Each domain is given a certain weight, which gives a score between 0 and 123 (higher score =worse symptoms). Low disease activity in ESSDAI was defined as ESSDAI score of less than 5 at Week 24.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With MCII in clinESSDAI at Week 24 | ||||||||||||
End point description |
Clinical (clin)ESSDAI includes the same 11 organ-specific domains as ESSDAI but with different domain weighting and without the biological domain. This way any change in clinESSDAI score would reflect disease specific features, irrespective of B-cell activity. The clinESSDAI score ranges between 0-135 (higher score = worse symptoms). Minimal clinically important improvement (MCII) in clinESSDAI was defined as improvement of at least 3 points in clinESSDAI score at Week 24.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Low Disease Activity in clinESSDAI at Week 24 | ||||||||||||
End point description |
clinESSDAI includes the same 11 organ-specific domains as ESSDAI but with different domain weighting and without the biological domain. This way any change in clinESSDAI score would reflect disease specific features, irrespective of B-cell activity. The clinESSDAI score ranges between 0-135 (higher score = worse symptoms). Low disease activity in clinESSDAI was defined as clinESSDAI score of less than 5 at Week 24.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With MCII in ESSPRI at Week 24 | ||||||||||||
End point description |
Minimal clinically important improvement in ESSPRI was defined as decrease of 1 point or at least ≥15% at Week 24. ESSPRI is a questionnaire that has been developed to measure self-reported symptoms in participants with pSjD. The score ranges from 0 (no symptoms) to 10 (more symptoms).
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in ESSDAI Score at Week 24 | ||||||||||||
End point description |
ESSDAI measures systemic disease activity in participants with pSjD and consists of 11 organ-specific domains and 1 biological domain that contribute to disease activity level scoring. Each domain is given a certain weight, which gives a score between 0 and 123 (higher score = worse symptoms).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in clinESSDAI Score at Week 24 | ||||||||||||
End point description |
clinESSDAI includes the same 11 organ-specific domains as ESSDAI but with different domain weighting and without the biological domain. This way any change in clinESSDAI score would reflect disease specific features, irrespective of B-cell activity. The clinESSDAI score ranges between 0-135 (higher score = worse symptoms).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in ESSPRI Score at Week 24 | ||||||||||||
End point description |
ESSPRI is a questionnaire that has been developed to measure self-reported symptoms in participants with pSjD. The score ranges from 0 (no symptoms) to 10 (more symptoms).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With STAR Score of at Least 5 at Week 24 | ||||||||||||
End point description |
Sjögren’s Tool for Assessing Response (STAR) is a composite endpoint assessing multiple clinically relevant disease features. A STAR responder is defined as a score of at least 5 points. Due to the weighting, participants must be a responder on either systemic disease activity (ESSDAI), patient-reported symptoms (ESSPRI), or both to be an overall STAR responder. The score ranges between 0 and 9 (higher score = worse outcome).
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Efgartigimod | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Serum samples were collected at indicated time points to assess the pharmacokinetic (PK) profile of efgartigimod. PK population included all randomized participants who received at least 1 dose of efgartigimod and had at least 1 measured concentration of efgartigimod at a scheduled PK time point. Here, n= number of participants with data collected for each specified category. "9999" indicates that mean and standard deviation could not be calculated as the values were below the lower limit of quantification (LLOQ). LLOQ was 200 ng/mL.
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End point type |
Secondary
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End point timeframe |
Pre-dose at Day 1, Weeks 1, 2, 4, 8, 12, 16, and 20; 30 minutes post-dose at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage Change From Baseline in Total IgG Levels in Serum at Week 24 | ||||||||||||
End point description |
Blood samples were collected at indicated timepoints to assess the total Immunoglobulin (Ig)G levels in serum. Only participants with data available at baseline and Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With ADA Against Efgartigimod in Serum | ||||||||||||||||||
End point description |
Blood samples were collected to assess anti-drug antibodies (ADAs) against efgartigimod. Treatment-boosted ADA was defined as participants who had a baseline positive sample and the titer value increased 4-fold or more compared to baseline. Treatment-induced ADA was defined as participants who had a baseline negative sample and at least 1 positive post-baseline samples. Treatment-unaffected ADA was defined as participants who had a baseline positive sample, but the titer value did not increase 4-fold or more compared to baseline.
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End point type |
Secondary
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End point timeframe |
Up to Week 24
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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 |
Up to 32 weeks.
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Adverse event reporting additional description |
The SAF included all participants exposed to the study treatment. Any abnormal laboratory results or changes in vital signs are captured in the adverse event listings.
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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 |
26.0
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Reporting groups
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Reporting group title |
Efgartigimod (SAF)
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Reporting group description |
Safety Analysis Set: Participants received efgartigimod 10 mg/kg once weekly via IV infusion for 24 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (SAF)
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Reporting group description |
Safety Analysis Set: Participants received placebo matched to efgartigimod once weekly via IV infusion for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Dec 2022 |
The primary rationale for this amendment was to permit the use of historic biopsy where taken within 12 months of enrollment to prevent participants from needing to undergo unnecessary procedures, and to update the permitted/excluded concomitant medications to allow participants to receive required therapy. Inclusion and exclusion were updated. Other clarifications and corrections were made. Minor editorial changes, including the correction of typographical errors and formatting inconsistencies were done.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
