Ignite Creation Date:
2024-05-06 @ 8:10 PM
Last Modification Date:
2024-10-26 @ 3:21 PM
Study NCT ID:
NCT06271018
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-21
First Post:
2024-02-14
Brief Title:
TocILizumab in aorTitis in GCA TILT
Sponsor:
GMIOFrance
Organization:
GMIOFrance
Study Overview
Official Title:
Prospective Observational Study Assessing Safety and Efficacy of Biosimilar of Tocilizumab in Giant Cell Arteritis GCA With Active Aortitis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TILT
Brief Summary:
This is a french multicenter observational study assessing safety and efficacy of biosimilar of Tocilizumab in Giant Cell Arteritis GCA with active aortitis including 14 reference centers from the Groupe dEtude Français des vascularites des gros vaisseaux GEFA
Giant Cell Arteritis GCA formerly known as temporal arteritis is the most common form of systemic vasculitis in patients aged 50 years GCA is defined by granulomatous arteritis that affects largesized and mediumsized blood vessels with a predisposition to affect the cranial arteries Aortitis accounted for more than 50 of GCA patients with the new imaging techniques Aortitis is typically diagnosed using imaging tests such as magnetic resonance imaging MRI or Computed Tomography CT scans Aortitis is an inflammation of the aorta leading to a range of symptoms such as fever weight loss fatigue and chest pain In severe cases aortic aneurysms or aortic dissection can occur which can be life-threatening
Multiple reports have demonstrated the presence of abnormal pro-inflammatory cytokine production in large-vessel vasculitis patients particularly those with GCA including interleukin-1 IL-1 IL-6 IL-18 tumor necrosis factor-α TNF-α and interferon-γ by T lymphocytes and macrophages IL-6 has been implicated as a crucial cytokine in the pathogenesis of aortitis and targeting its signaling has shown promising results in treating the condition IL-6 inhibitors such as tocilizumab have been found to effectively reduce disease activity and improve clinical outcomes in GCA patients
The GIACTA study GiAnt cell arteritis roActemra tocilizumab study was a randomized double-blind placebo-controlled trial that evaluated the efficacy and safety of tocilizumab in the treatment of GCA The study included 251 patients with newly diagnosed or relapsing GCA and found that treatment with tocilizumab significantly increased the proportion of patients who achieved sustained remission from GCA at 52 weeks compared to placebo Additionally tocilizumab was associated with a lower incidence of disease flares and a reduced need for glucocorticoid therapy
Following the positive results of the GIACTA study tocilizumab was approved for the treatment of GCA in adults with active disease including aortitis who have not responded to glucocorticoids or for whom glucocorticoid therapy is not appropriate by regulatory agencies around the world including the US Food and Drug Administration and the European Medicines Agency
However the efficacy of IL-6 inhibitors on aorta inflammation as assessed by modern and powerful imaging techniques has never been specifically studied in GCA
This observational study will provide important informations on the impact of Tyenne tocilizumab associated with short term low dose steroids on clinical manifestations and vessel inflammation and damage in aortitis of GCA
Giant Cell Arteritis GCA formerly known as temporal arteritis is the most common form of systemic vasculitis in patients aged 50 years GCA is defined by granulomatous arteritis that affects largesized and mediumsized blood vessels with a predisposition to affect the cranial arteries Aortitis accounted for more than 50 of GCA patients with the new imaging techniques Aortitis is typically diagnosed using imaging tests such as magnetic resonance imaging MRI or Computed Tomography CT scans Aortitis is an inflammation of the aorta leading to a range of symptoms such as fever weight loss fatigue and chest pain In severe cases aortic aneurysms or aortic dissection can occur which can be life-threatening
Multiple reports have demonstrated the presence of abnormal pro-inflammatory cytokine production in large-vessel vasculitis patients particularly those with GCA including interleukin-1 IL-1 IL-6 IL-18 tumor necrosis factor-α TNF-α and interferon-γ by T lymphocytes and macrophages IL-6 has been implicated as a crucial cytokine in the pathogenesis of aortitis and targeting its signaling has shown promising results in treating the condition IL-6 inhibitors such as tocilizumab have been found to effectively reduce disease activity and improve clinical outcomes in GCA patients
The GIACTA study GiAnt cell arteritis roActemra tocilizumab study was a randomized double-blind placebo-controlled trial that evaluated the efficacy and safety of tocilizumab in the treatment of GCA The study included 251 patients with newly diagnosed or relapsing GCA and found that treatment with tocilizumab significantly increased the proportion of patients who achieved sustained remission from GCA at 52 weeks compared to placebo Additionally tocilizumab was associated with a lower incidence of disease flares and a reduced need for glucocorticoid therapy
Following the positive results of the GIACTA study tocilizumab was approved for the treatment of GCA in adults with active disease including aortitis who have not responded to glucocorticoids or for whom glucocorticoid therapy is not appropriate by regulatory agencies around the world including the US Food and Drug Administration and the European Medicines Agency
However the efficacy of IL-6 inhibitors on aorta inflammation as assessed by modern and powerful imaging techniques has never been specifically studied in GCA
This observational study will provide important informations on the impact of Tyenne tocilizumab associated with short term low dose steroids on clinical manifestations and vessel inflammation and damage in aortitis of GCA
Detailed Description:
This is a prospective observational study involving patients with active aortitis related to GCA
After verification of the inclusion and exclusion criteria and signature of the consent form patients are included in the study Patients will be followed and managed according to standard of care visits and exams
Oral corticosteroids must be at a stable dose for at least 2 weeks prior to the first administration of study drug at D0
All patients will receive oral prednisone 10 mgday or oral corticosteroid equivalent with a maximum of 60 mgday of prednisone or equivalent
A standardized prednisone reduction schedule see below will be applied to all groups as long as the disease is inactive until prednisone is stopped The aim is to taper off corticosteroids within eight weeks
At D0 MSB11456 1 injection SC weekly will be initiated
Blood samples will be taken every month up to week 52 for assessment of toxicity and inflammation markers
Assessment of adverse events will be done routinely at weeks 12 24 36 52 and 104
Clinical evaluation will be performed routinely at weeks 12 24 36 52 and 104
Targeted imaging studies angio-CT will be performed routinely at 6 12 and 24 months after the start of treatment and if new symptoms appear
FDG Pet scan will be performed routinely at 6 12 and 24 months after the start of treatment
Angio-CT and FDG Pet scan will be proofread centrally A standardized prednisone reduction schedule see below will be applied to all patients as long as the disease is inactive until prednisone is stopped
Baseline prednisone dose Corresponding dose mgday at each week
CGmgd ____60_____50_____40_____30_____25_____20_____15____10____75 at baseline
60__________W0
50__________W1____W0
40__________W2____W1____W0
30__________W3____W2____W1____W0
25___________ - ____W3____W2____W1____W0
20__________W4____W4____W3____W2____W1____W0
15__________W5____W5____W4____W3____W2____W1____W0
10__________W6____W6____W5____W4____W3____W2____W2____W0
75__________ - _____ - _____ - _____W5____W4____W3____W3____W1____W0
5 ___________W7____W7____W6____W6____W5____W4____W4____W2____W2
0 ___________W8____W8____W7____W7____W6____W6____W5____W4____W4
Sample size
We anticipated a remission rate of 70 at weel 24 based on pooled data from Viliger et al 1 and Stone et al 2 Viliger et al reported 85 of GCA remission at week 12 and week 52 with tocilizumab1 Stone et al reported 56 of remission of GCA at week 52 under tocilizumab weekly with less than 10 of relpases between week 24 and week 52 2 A total of 80 patients will ensure estimating the 24-week remission rate with a precision of - 11 using an exact 95 confidence intervalgiven the expected 70 remission rate
Statistical analysis
Descriptive analyses will be performed with counts and percent for discrete variables and median and interquartile range for continuous variables The primary endpoint will be described with the 24-week remission proportion point estimate and its exact 95 confidence interval 95CI Clopper Pearson Secondary endpoints will be described using a similar approach for binary endpointscontinuous endpoints will be decsribed unsing median IQR and also mean SD with approximate Gaussian 95CI for the meanKaplan Meier estimator or cumulative incidence estimates allowing competing risks when appropriate ie treatment discontinuation due to toxicity will be used for right-ecensored time to event variables with 95 confidence intervals
After verification of the inclusion and exclusion criteria and signature of the consent form patients are included in the study Patients will be followed and managed according to standard of care visits and exams
Oral corticosteroids must be at a stable dose for at least 2 weeks prior to the first administration of study drug at D0
All patients will receive oral prednisone 10 mgday or oral corticosteroid equivalent with a maximum of 60 mgday of prednisone or equivalent
A standardized prednisone reduction schedule see below will be applied to all groups as long as the disease is inactive until prednisone is stopped The aim is to taper off corticosteroids within eight weeks
At D0 MSB11456 1 injection SC weekly will be initiated
Blood samples will be taken every month up to week 52 for assessment of toxicity and inflammation markers
Assessment of adverse events will be done routinely at weeks 12 24 36 52 and 104
Clinical evaluation will be performed routinely at weeks 12 24 36 52 and 104
Targeted imaging studies angio-CT will be performed routinely at 6 12 and 24 months after the start of treatment and if new symptoms appear
FDG Pet scan will be performed routinely at 6 12 and 24 months after the start of treatment
Angio-CT and FDG Pet scan will be proofread centrally A standardized prednisone reduction schedule see below will be applied to all patients as long as the disease is inactive until prednisone is stopped
Baseline prednisone dose Corresponding dose mgday at each week
CGmgd ____60_____50_____40_____30_____25_____20_____15____10____75 at baseline
60__________W0
50__________W1____W0
40__________W2____W1____W0
30__________W3____W2____W1____W0
25___________ - ____W3____W2____W1____W0
20__________W4____W4____W3____W2____W1____W0
15__________W5____W5____W4____W3____W2____W1____W0
10__________W6____W6____W5____W4____W3____W2____W2____W0
75__________ - _____ - _____ - _____W5____W4____W3____W3____W1____W0
5 ___________W7____W7____W6____W6____W5____W4____W4____W2____W2
0 ___________W8____W8____W7____W7____W6____W6____W5____W4____W4
Sample size
We anticipated a remission rate of 70 at weel 24 based on pooled data from Viliger et al 1 and Stone et al 2 Viliger et al reported 85 of GCA remission at week 12 and week 52 with tocilizumab1 Stone et al reported 56 of remission of GCA at week 52 under tocilizumab weekly with less than 10 of relpases between week 24 and week 52 2 A total of 80 patients will ensure estimating the 24-week remission rate with a precision of - 11 using an exact 95 confidence intervalgiven the expected 70 remission rate
Statistical analysis
Descriptive analyses will be performed with counts and percent for discrete variables and median and interquartile range for continuous variables The primary endpoint will be described with the 24-week remission proportion point estimate and its exact 95 confidence interval 95CI Clopper Pearson Secondary endpoints will be described using a similar approach for binary endpointscontinuous endpoints will be decsribed unsing median IQR and also mean SD with approximate Gaussian 95CI for the meanKaplan Meier estimator or cumulative incidence estimates allowing competing risks when appropriate ie treatment discontinuation due to toxicity will be used for right-ecensored time to event variables with 95 confidence intervals
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None