Ignite Creation Date:
2024-05-06 @ 11:12 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03465111
Status:
RECRUITING
Last Update Posted:
2023-10-23
First Post:
2018-02-16
Brief Title:
A Clinical Study to Evaluate the Potential Role of ACTH Gel in Patients With Scleritis
Sponsor:
Metropolitan Eye Research Surgery Institute
Organization:
Metropolitan Eye Research Surgery Institute
Study Overview
Official Title:
An Open Label Multi-centered Randomized Phase 2 Study to Evaluate the Safety Tolerability and Bioactivity of Subcutaneous ACTH GeL in PAtients With Scleritis The ATLAS Study
Status:
RECRUITING
Status Verified Date:
2023-10
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:
ATLAS
Brief Summary:
ATLAS study is a clinical trial to evaluate the potential role of subcutaneous adrenocorticotropic hormone ACTH gel in the management of non-infectious scleritis
Specifically the ATLAS Study aims to evaluate the safety tolerability and effect of 2 different dose regimens of ACTH gel administered by subcutaneous SC injection in patients with scleritis over a period of 12 months
Scleritis is an inflammatory disease affecting the sclera white outer coating of the eye which causes blurring of vision redness tearing and painful ocular inflammatory episodes in one or both eyes Scleritis may results in vision threatening ocular complications if left untreated Treatment of scleritis is usually chronic and requires systemic therapy with non-steroidal anti-inflammatory drugs corticosteroids and immunosuppressive therapy Due to its treatment resistance nature scleritis remains a therapeutic challenge for many ophthalmologists
HP Acthar Gel ACTH Gel is a highly purified preparation of adrenocorticotropic hormone ACTH in a gel that is designed to provide extended release of the ACTH following injection It is a FDA approved treatment for flares or on a regular basis maintenance in people with systemic lupus erythematosus lupus infantile spasms adults with acute relapses or flares of multiple sclerosis MS patients with kidney diseases among other indications ACTH Gel is also approved for a wide range of allergic and inflammatory diseases of the eye
Given the established role of inflammation in the pathogenesis of scleritis and the anti-inflammatory effects of ACTH Gel treatment by blocking various inflammatory pathways a beneficial outcome could be anticipated from ACTH Gel treatment in patients with scleritis
Specifically the ATLAS Study aims to evaluate the safety tolerability and effect of 2 different dose regimens of ACTH gel administered by subcutaneous SC injection in patients with scleritis over a period of 12 months
Scleritis is an inflammatory disease affecting the sclera white outer coating of the eye which causes blurring of vision redness tearing and painful ocular inflammatory episodes in one or both eyes Scleritis may results in vision threatening ocular complications if left untreated Treatment of scleritis is usually chronic and requires systemic therapy with non-steroidal anti-inflammatory drugs corticosteroids and immunosuppressive therapy Due to its treatment resistance nature scleritis remains a therapeutic challenge for many ophthalmologists
HP Acthar Gel ACTH Gel is a highly purified preparation of adrenocorticotropic hormone ACTH in a gel that is designed to provide extended release of the ACTH following injection It is a FDA approved treatment for flares or on a regular basis maintenance in people with systemic lupus erythematosus lupus infantile spasms adults with acute relapses or flares of multiple sclerosis MS patients with kidney diseases among other indications ACTH Gel is also approved for a wide range of allergic and inflammatory diseases of the eye
Given the established role of inflammation in the pathogenesis of scleritis and the anti-inflammatory effects of ACTH Gel treatment by blocking various inflammatory pathways a beneficial outcome could be anticipated from ACTH Gel treatment in patients with scleritis
Detailed Description:
ATLAS is an Investigator-initiated open-labelled multi-center randomized phase II clinical trial to evaluate the effect of two dose regimens of subcutaneous ACTH gel in subjects with non-infectious anterior scleritis over a period of 12 months 52 weeks with the primary endpoint at month 4 week 16 ATLAS study will be conducted at up to 6 clinical sites in USA The study will be coordinated by the Ocular Imaging Research and Reading Center OIRRC which will serve as the coordinating and reading center for the ATLAS Study
The ATLAS Study aims to evaluate the potential role of subcutaneous adrenocorticotropic hormone ACTH gel in the management of non-infectious anterior scleritis Specifically the ATLAS Study aims to evaluate the safety and tolerability of 2 different dose regimens of ACTH gel administered by subcutaneous SC injection in patients with non-infectious anterior scleritis and to evaluate the bioactivity of 2 different dose regimens of ACTH gel administered by SC injection in patients with non-infectious anterior scleritis
Scleritis refers to red and painful inflammation centered in the sclera that may involve adjacent ocular structures including the cornea episclera and uvea Scleritis may results in vision threatening ocular complications corneal ulceration cataract glaucoma retinal detachment choroidal effusion and subsequent blindness Up to 50 of patients with scleritis have an associated systemic inflammatory disorder such as sarcoidosis rheumatoid arthritis systemic lupus erythematosus and polyangiitis with granulomatosis Scleritis is classified based on the anatomic site as anterior or posterior with 90 of cases anterior Anterior scleritis may manifest as necrotizing or non-necrotizing Non-necrotizing noninfectious scleritis is the most prevalent form The course of scleritis is usually chronic similar to uveitis and requires systemic therapy with non-steroidal anti-inflammatory drugs and glucocorticoids along with immunosuppression as steroid-sparing therapy Due to its treatment resistance nature scleritis remains a therapeutic challenge for many ophthalmologists The ultimate goal is to control the inflammation which serves as the cornerstone of the scleritis pathophysiological basis
Adrenocorticotropic hormone ACTH is a member of a group of peptide hormones called melanocortins MCs ACTH is released from the pituitary gland and acts primarily on the adrenals to stimulate and regulate steroid hormones production It has been demonstrated that MCs can be produced by immune cells at the inflammation site which created a special interest in immunomodulatory properties of these peptides Latest evidence proposes other anti-inflammatory mechanisms of ACTH actions in addition to steroidogenesis including leukocyte transmigration inhibition cytokine synthesis reduction and generation of anti-inflammatory signals locally at the inflammation site ACTH gel has been reported to be effective in various systemic inflammatory diseases including nephrotic syndrome multiple sclerosis opsoclonus myoclonusdermatomyositis and polymyositis These reports also include cases that were resistant to steroids and other immunomodulatory drugs supporting the immune-modulating properties of ACTH HP Acthar Gel Repository Corticotropin Injection Mallinckrodt Pharmaceuticals is a 39-amino-acid pituitary-derived ACTH analogue ACTH gel has been demonstrated to have additional therapeutic effects on the humoral immune system independent of its role in the adrenal steroidogenesis regulation It is approved by the US FDA for treatment of a number of inflammatory conditions including multiple sclerosis rheumatic and collagen disorders as well as ophthalmologic diseases such as ocular allergy keratitis uveitis and optic neuritis However due to the scarcity of data from clinical studies many physicians are unaware of ACTH gel as a treatment option for inflammatory diseases
The proposed study aims to evaluate the potential role of ACTH gel in the management of non-infectious anterior scleritis Given the established role of inflammation in the pathogenesis of scleritis and the ability of ACTH to bind to cellular and tissue melanocortin receptors thus blocking various inflammatory pathways a beneficial outcome could be anticipated from ACTH analogue in patients with scleritis
Thirty 30 subjects with non-infectious anterior scleritis will be enrolled in the study
The primary endpoint of the study will be at week 16 with an active as-needed treatment extension phase from week 17 to week 52
All study participants will be randomized 11 at their Baseline BL visit visit 2 to one of the two treatment arms All subjects will be started on oral corticosteroids at a maximum dosage of 1 mgkg of prednisone or equivalence a day at the screening visit which will continue to be administered at the same dose throughout the screening period until BLVisit 2 Steroid dose will be tapered from BLVisit 2 onwards until week 9 Visit 5 If the scleritis is still greater than 05 on the grading scale the investigators have the discretion to continue on the tapering course of steroid while the subjects are also being treated with ACTH gel
The two treatment arms are as follows
1 Mandatory 80 U twice weekly treatment with SC ACTH gel starting at the Baseline visit Day 0 until end of week 16
2 Mandatory 80 U thrice weekly treatment with SC ACTH gel starting at the Baseline visit Day 0 until end of week 16
Starting at week 17 treatment regimen will be determined according to clinical response to treatment as follows
1 No evidence of active diseasedisease resolved - treatment dose will be reduced to 80 U once a week with SC ACTH gel
2 Evidence of disease improvement but still activepartial response - ACTH treatment will continue alone at the pre-assigned treatment dose Steroids will not be added to the treatment due to several side effects of the combination of the drugs
3 No evidence of improvementdisease progression - treatment with ACTH gel will be discontinued and rescue therapy will be initiated as per investigator based on standard of care
At the primary end point week 16 and at the end of follow-up period week 52 efficacy will be assessed by standard ophthalmic examination procedures and response to treatment which will be graded according to established scleritis grading scale Evaluation of response will be based on changes in scleral inflammation grade at various time points during the study changes in pain grade scale at various time points during the study changes in the dosage of prednisone required to maintain disease quiescence and stability and changes on ancillary testing such as FA OCT among others Retreatment will be offered to study subjects who have demonstrated any level of response during the first 16 weeks and who meet any of the Retreatment Criteria listed below Subjects receiving retreatment will receive the dose that was assigned to them at randomization There is no placebo arm in this study
The ATLAS Study aims to evaluate the potential role of subcutaneous adrenocorticotropic hormone ACTH gel in the management of non-infectious anterior scleritis Specifically the ATLAS Study aims to evaluate the safety and tolerability of 2 different dose regimens of ACTH gel administered by subcutaneous SC injection in patients with non-infectious anterior scleritis and to evaluate the bioactivity of 2 different dose regimens of ACTH gel administered by SC injection in patients with non-infectious anterior scleritis
Scleritis refers to red and painful inflammation centered in the sclera that may involve adjacent ocular structures including the cornea episclera and uvea Scleritis may results in vision threatening ocular complications corneal ulceration cataract glaucoma retinal detachment choroidal effusion and subsequent blindness Up to 50 of patients with scleritis have an associated systemic inflammatory disorder such as sarcoidosis rheumatoid arthritis systemic lupus erythematosus and polyangiitis with granulomatosis Scleritis is classified based on the anatomic site as anterior or posterior with 90 of cases anterior Anterior scleritis may manifest as necrotizing or non-necrotizing Non-necrotizing noninfectious scleritis is the most prevalent form The course of scleritis is usually chronic similar to uveitis and requires systemic therapy with non-steroidal anti-inflammatory drugs and glucocorticoids along with immunosuppression as steroid-sparing therapy Due to its treatment resistance nature scleritis remains a therapeutic challenge for many ophthalmologists The ultimate goal is to control the inflammation which serves as the cornerstone of the scleritis pathophysiological basis
Adrenocorticotropic hormone ACTH is a member of a group of peptide hormones called melanocortins MCs ACTH is released from the pituitary gland and acts primarily on the adrenals to stimulate and regulate steroid hormones production It has been demonstrated that MCs can be produced by immune cells at the inflammation site which created a special interest in immunomodulatory properties of these peptides Latest evidence proposes other anti-inflammatory mechanisms of ACTH actions in addition to steroidogenesis including leukocyte transmigration inhibition cytokine synthesis reduction and generation of anti-inflammatory signals locally at the inflammation site ACTH gel has been reported to be effective in various systemic inflammatory diseases including nephrotic syndrome multiple sclerosis opsoclonus myoclonusdermatomyositis and polymyositis These reports also include cases that were resistant to steroids and other immunomodulatory drugs supporting the immune-modulating properties of ACTH HP Acthar Gel Repository Corticotropin Injection Mallinckrodt Pharmaceuticals is a 39-amino-acid pituitary-derived ACTH analogue ACTH gel has been demonstrated to have additional therapeutic effects on the humoral immune system independent of its role in the adrenal steroidogenesis regulation It is approved by the US FDA for treatment of a number of inflammatory conditions including multiple sclerosis rheumatic and collagen disorders as well as ophthalmologic diseases such as ocular allergy keratitis uveitis and optic neuritis However due to the scarcity of data from clinical studies many physicians are unaware of ACTH gel as a treatment option for inflammatory diseases
The proposed study aims to evaluate the potential role of ACTH gel in the management of non-infectious anterior scleritis Given the established role of inflammation in the pathogenesis of scleritis and the ability of ACTH to bind to cellular and tissue melanocortin receptors thus blocking various inflammatory pathways a beneficial outcome could be anticipated from ACTH analogue in patients with scleritis
Thirty 30 subjects with non-infectious anterior scleritis will be enrolled in the study
The primary endpoint of the study will be at week 16 with an active as-needed treatment extension phase from week 17 to week 52
All study participants will be randomized 11 at their Baseline BL visit visit 2 to one of the two treatment arms All subjects will be started on oral corticosteroids at a maximum dosage of 1 mgkg of prednisone or equivalence a day at the screening visit which will continue to be administered at the same dose throughout the screening period until BLVisit 2 Steroid dose will be tapered from BLVisit 2 onwards until week 9 Visit 5 If the scleritis is still greater than 05 on the grading scale the investigators have the discretion to continue on the tapering course of steroid while the subjects are also being treated with ACTH gel
The two treatment arms are as follows
1 Mandatory 80 U twice weekly treatment with SC ACTH gel starting at the Baseline visit Day 0 until end of week 16
2 Mandatory 80 U thrice weekly treatment with SC ACTH gel starting at the Baseline visit Day 0 until end of week 16
Starting at week 17 treatment regimen will be determined according to clinical response to treatment as follows
1 No evidence of active diseasedisease resolved - treatment dose will be reduced to 80 U once a week with SC ACTH gel
2 Evidence of disease improvement but still activepartial response - ACTH treatment will continue alone at the pre-assigned treatment dose Steroids will not be added to the treatment due to several side effects of the combination of the drugs
3 No evidence of improvementdisease progression - treatment with ACTH gel will be discontinued and rescue therapy will be initiated as per investigator based on standard of care
At the primary end point week 16 and at the end of follow-up period week 52 efficacy will be assessed by standard ophthalmic examination procedures and response to treatment which will be graded according to established scleritis grading scale Evaluation of response will be based on changes in scleral inflammation grade at various time points during the study changes in pain grade scale at various time points during the study changes in the dosage of prednisone required to maintain disease quiescence and stability and changes on ancillary testing such as FA OCT among others Retreatment will be offered to study subjects who have demonstrated any level of response during the first 16 weeks and who meet any of the Retreatment Criteria listed below Subjects receiving retreatment will receive the dose that was assigned to them at randomization There is no placebo arm in this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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