Ignite Creation Date:
2024-05-06 @ 3:19 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04598815
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-03-15
First Post:
2020-10-16
Brief Title:
Sirolimus for Graves Orbitopathy GO
Sponsor:
University of Pisa
Organization:
University of Pisa
Study Overview
Official Title:
A Phase II Randomized Superiority Adaptive Open-label Single-center Clinical Trial to Evaluate the Efficacy of Sirolimus Rapamycin in Patients With Graves Disease and Moderate-to-severe and Active Graves Orbitopathy GO
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-03
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:
SIRGO
Brief Summary:
Graves Orbitopathy GO is a disabling and disfiguring condition associated with Graves Disease due to autoimmunity against antigens expressed by the thyroid and orbital tissues and resulting in orbital fibroblast proliferation and release of glycosaminoglycans The current treatments available especially glucocorticoids are not effective in all patients Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug
The rationale for the use of Sirolimus lies in its mechanisms of action Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation In addition acts indirectly on the Insulin-Like Growth Factor-1 IGF-1 pathway and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor Teprotumumab is effective in patients with GO Thus Sirolimus could be used in GO as monotherapy in patients with GO
The aim of the present drug vs standard treatment open-label randomized clinical trial is to evaluate the efficacy of Sirolimus in patients with moderately severe active GO
54 patients 27 per group will be randomized into two groups A and B Patients in group A will receive Sirolimus for 12 weeks Patients in group B will receive methylprendnisolone for 12 weeks
The primary objective of the study is the response of GO at 24 weeks based on a composite evaluation The secondary Objectives will be 1 the response of of GO at 12 36 and 48 weeks 2 Relapse of GO at 36 and 48 weeks worsening compared with the 24-week evaluation 3 The reduction of proptosis at 12 24 36 and 48 weeks proportion of patients with a reduction of proptosis of at least 2 mm 4 Reduction of the GO clinical activity score CAS at 12 24 36 and 48 weeks 5 Quality of life Qol at 12 24 36 and 48 weeks
The safety objectives will be adverse events adverse drug reactions unexpected adverse reaction suspected unexpected adverse reactions and death across the study and at 12 24 36 and 48 weeks
The rationale for the use of Sirolimus lies in its mechanisms of action Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation In addition acts indirectly on the Insulin-Like Growth Factor-1 IGF-1 pathway and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor Teprotumumab is effective in patients with GO Thus Sirolimus could be used in GO as monotherapy in patients with GO
The aim of the present drug vs standard treatment open-label randomized clinical trial is to evaluate the efficacy of Sirolimus in patients with moderately severe active GO
54 patients 27 per group will be randomized into two groups A and B Patients in group A will receive Sirolimus for 12 weeks Patients in group B will receive methylprendnisolone for 12 weeks
The primary objective of the study is the response of GO at 24 weeks based on a composite evaluation The secondary Objectives will be 1 the response of of GO at 12 36 and 48 weeks 2 Relapse of GO at 36 and 48 weeks worsening compared with the 24-week evaluation 3 The reduction of proptosis at 12 24 36 and 48 weeks proportion of patients with a reduction of proptosis of at least 2 mm 4 Reduction of the GO clinical activity score CAS at 12 24 36 and 48 weeks 5 Quality of life Qol at 12 24 36 and 48 weeks
The safety objectives will be adverse events adverse drug reactions unexpected adverse reaction suspected unexpected adverse reactions and death across the study and at 12 24 36 and 48 weeks
Detailed Description:
Study Design Phase II randomized adaptive superiority open-label single-center pilot clinical trial
Fifty-four patients with moderate-to-severe and active GO will be randomized into two intervention groups A and B with a ratio of 1 1 Subjects assigned to group A will receive Sirolimus for 12 weeks Patients assigned to group B will receive a cumulative dose of 45 g of methylprednisolone divided into 12 weekly infusions This treatment scheme is the clinical standard and patients would be treated with methylprednisolone in any case even if they did not accept to participate to the study
Enrollment duration 24 months Study duration 36 months Tentative start of trial July 1st 2022
Study Population Fifty-four patients with Graves disease and GO will be recruited during the routine clinical activity carried out at the Endocrinology Unit II of AOUP which is a tertiary referral center for thyroid diseases
Study Timeline
Screening visit 2-6 weeks before the first visit
1st baseline visit - Time 0 randomization and administration of the first dose of trial agent
Treatment period week 1-week 12 daily administration of the trial agent Sirolimus or weekly administration of the standard treatment methylprednisolone
Methylprednisolone treatment period and treatment visits week 2-week 13 weekly methylprednisolone administrations week 2-week 13
Safety visits week 3 5 7 9 11
2nd visit week 12
3rd visit week 24
4th visit week 36
5th visit week 48
Fifty-four patients with moderate-to-severe and active GO will be randomized into two intervention groups A and B with a ratio of 1 1 Subjects assigned to group A will receive Sirolimus for 12 weeks Patients assigned to group B will receive a cumulative dose of 45 g of methylprednisolone divided into 12 weekly infusions This treatment scheme is the clinical standard and patients would be treated with methylprednisolone in any case even if they did not accept to participate to the study
Enrollment duration 24 months Study duration 36 months Tentative start of trial July 1st 2022
Study Population Fifty-four patients with Graves disease and GO will be recruited during the routine clinical activity carried out at the Endocrinology Unit II of AOUP which is a tertiary referral center for thyroid diseases
Study Timeline
Screening visit 2-6 weeks before the first visit
1st baseline visit - Time 0 randomization and administration of the first dose of trial agent
Treatment period week 1-week 12 daily administration of the trial agent Sirolimus or weekly administration of the standard treatment methylprednisolone
Methylprednisolone treatment period and treatment visits week 2-week 13 weekly methylprednisolone administrations week 2-week 13
Safety visits week 3 5 7 9 11
2nd visit week 12
3rd visit week 24
4th visit week 36
5th visit week 48
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?:
False
Is an FDA AA801 Violation?:
None