Clinical Trial Results:
A 28-week, randomized, double-blind, active-controlled, multicenter study to evaluate the efficacy of subcutaneously administered secukinumab compared to ustekinumab in adult patients with psoriatic arthritis and failure of TNFα-inhibitor treatment (AgAIN)
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Summary
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EudraCT number |
2022-001516-26 |
Trial protocol |
DE |
Global end of trial date |
18 Dec 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Nov 2025
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First version publication date |
23 Nov 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 |
CAIN457FDE05
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05569174 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
Novartis Campus, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Dec 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 |
18 Dec 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 |
The main objective was to demonstrate the superiority of 12 weeks of treatment with secukinumab 300 mg (subcutaneous) compared to placebo (both arms in combination with patient individualized conventional therapy), in participants with moderate to severe rotator cuff tendinopathy, based on change in Western Ontario Rotator Cuff index (WORC) score from Baseline to Week 24.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Dec 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 62
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Worldwide total number of subjects |
62
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EEA total number of subjects |
62
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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) |
61
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were randomized in 19 study sites across Germany | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 100 participants were screened and 62 participants were randomized in nearly equal numbers to the 2 treatment groups (secukinumab: N=30; placebo: N=32) and received study treatment | |||||||||||||||||||||||||||
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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, Monitor, Carer, Data analyst, 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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Secukinumab | |||||||||||||||||||||||||||
Arm description |
Participants received 300 mg of secukinumab s.c. for 12 weeks | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Secukinumab
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Investigational medicinal product code |
AIN457
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe, Solution for infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Secukinumab 300 mg subcutaneosly for 12 weeks in a pre-filled syringe (PFS)
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Participants received placebo s.c. for 12 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 |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo to match secukinumab s.c. for 12 weeks in a PFS
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Baseline characteristics reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Participants received 300 mg of secukinumab s.c. for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo s.c. for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Participants received 300 mg of secukinumab s.c. for 12 weeks | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo s.c. for 12 weeks | ||
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End point title |
Change from baseline in the Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Percentage Score at Week 24 [1] | ||||||||||||
End point description |
The WORC Index consisted of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). Each of the 21 items in the WORC was rated using a visual analogue scale (VAS) ranging from 0 (no impact on quality of life) to 100 (worst possible impact). Thus, the total score ranged from 0 to 2100 points. The score was reported as a percentage of normal by subtracting the total score from 2100, dividing by 2100, and multiplying by 100. Total final WORC percentage scores ranged from 0%, the lowest functional status level, to 100%, the highest functional status level.
Change from baseline in the WORC percentage total score was assessed at Week 24. A positive change from baseline indicated an improvement.
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End point type |
Primary
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End point timeframe |
Baseline, 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: No statistical analyses are disclosed for this primary end point |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in the WORC percentage sub-scores at Week 24 | |||||||||||||||||||||||||||
End point description |
The WORC Index consisted of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). Each of the 21 items in the WORC was rated using a VAS ranging from 0 (no impact on quality of life) to 100 (worst possible impact).
Each subdomain score was calculated as a percentage of normal function, ranging from 0% (worst condition) to 100% (best condition).
Change from baseline in the WORC Index percentage sub-domain score was assessed at Week 24. A positive change from baseline indicated an improvement
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Change from baseline in Participant's Global Assessment of Disease Activity Score at Week 24 | ||||||||||||
End point description |
The participant’s global assessment of disease activity was performed using 100 mm VAS ranging from 0=“no activity” to 100= “most active”, after the question " Please indicate with a vertical mark ( | ) through the horizontal line the global activity of your disease in the last 24 hours”.
Change from baseline in the participant's global assessment of disease activity score was assessed at Week 24. A negative change from baseline indicated improvement
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in Short Form 36 (SF-36v2) Score at Week 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The SF-36 Health Survey was a validated questionnaire assessing health-related quality of life. Participants completed the survey throughout the study, reflecting their health status over the previous 4 weeks. It consisted of eight subscales that were scored individually; and two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component summary scores (PCS and MCS) were derived from weighted combinations of the eight subscales. Each domain and component summary score ranged from 0 to 100, with higher scores indicating better quality of life.
Change from baseline to Week 24 in all subscale and summary scores was assessed, where a positive change indicated improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in Quick Disability of the Arm, Shoulder and Hand (DASH) questionnaire Score at Week 24 | ||||||||||||
End point description |
The QuickDASH was an abbreviated form of the DASH. The QuickDASH Index was self-administered and used 11 items to measure physical function and symptoms in participants with any or multiple musculoskeletal disorders of the upper limb. It had a recall period of 1 week. Each item of the QuickDASH had five response options. The total score was reported on a 100-point scale, with 100 indicating the most disability.
Change from baseline to Week 24 was assessed. A negative change from baseline indicated improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in the Numeric Rating Scale (NRS) pain score at Week 24 | ||||||||||||
End point description |
The score for pain was assessed by using an 11-point NRS ranging from 0 “no pain at all” to 10 “worst possible pain”, after the question “On a numeric scale of 0–10 where would you rate your pain at this time”.
Change from baseline to Wek 24 was assessed. A negative change from baseline indicated improvement
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in EuroQol 5 Dimensions- 5 Levels (EQ-5D-5L) at Week 24- Total Score | ||||||||||||
End point description |
The EQ-5D-5L was a standardized instrument used to evaluate patients’ overall health-related quality of life (QoL). It consisted of two components: the descriptive system and the EQ visual analogue scale (EQ VAS).
The descriptive system assessed five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension was rated on five levels, from 1 (no problems) to 5 (extreme problems). These ratings were combined to generate a composite health index, which could be converted into a single summary health utility score using published value sets. Total scores ranged from 0 to 1, with lower scores indicating greater health impairment.
Changes in total scores from baseline to Week 24 were analyzed, with positive changes indicating improvement in health-related quality of life.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in EuroQol 5 Dimensions- 5 Levels (EQ-5D-5L) at Week 24- EQ VAS | ||||||||||||
End point description |
The EQ-5D-5L was a standardized instrument used to evaluate patients’ overall health-related quality of life (QoL). It consisted of two components: the descriptive system and the EQ visual analogue scale (EQ VAS).
The EQ VAS captured the respondent’s self-rated health on a vertical scale ranging from 0 (worst imaginable health) to 100 (best imaginable health).
Changes in EQ VAS scores from baseline to Week 24 were analyzed, with positive changes indicating improvement in health-related quality of life.
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End point type |
Secondary
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End point timeframe |
Baseline, 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 |
From start of treatment to end of study, assessed up to approximately 24 weeks
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Adverse event reporting additional description |
The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
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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 |
27.1
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Reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Secukinumab 300 mg s.c for 12 weeks in a PFS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo to match secukinumab s.c. for 12 weeks in a PFS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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12 Jun 2023 |
- Update of inclusion criteria describing the severity of the symptoms
- Omission of ECG assessments
- Inclusion of high sensitivity CRP as laboratory parameter in clinical chemistry
- Addition of optional WORC PRO at screening
- Clarification on X-Ray assessment
- Update on study length justification
- Clarification of Run-in phase definition |
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10 Jul 2024 |
- Clarification that painful arc test needs to be “positive” for inclusion
- Clarification regarding non-NSAID medication as additional study treatment
- Removal that discontinuation is required in case of 2 missed doses
- Clarification that paper-based PROs can be used as backup
- Clarification that adverse events are monitored depending on last dose of study treatment
- Inclusion of Hy’s law language for SAEs
- Addition of the section “Reporting of study treatment errors, study treatment misuse/abuse and overdose”.
- Update of primary endpoint analysis to reflect that analysis was to be only descriptive due to early termination of screening. |
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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. | |||
| Due to the limited sample size, the results are not statistically significant, and no conclusions regarding efficacy or lack thereof can be drawn. | |||
