ScleritisPhase 2ATLASNCT03465111
A Clinical Study to Evaluate the Potential Role of ACTH Gel in Patients With Scleritis
A Phase 2 study testing ACTH (adrenocorticotropic hormone) gel in people with Scleritis, run by Metropolitan Eye Research & Surgery Institute at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleritis
- What is being tested?
- ACTH (adrenocorticotropic hormone) gel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Jan 2019to 8 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults, age ≥ 18 years;
- Able to give informed consent and attend all study visits;
- Have diagnosis of non-necrotizing scleritis determined by the Investigator to be non-infectious;
- Have active scleirits, defined as:
- Characteristic clinical presentation of active disease: painful inflammation, edema and tenderness to touch radiating to the forehead, the brow, the jaw, or the sinuses. Severity of pain associated with scleritis will be based on pain intensity, NRS scale.
- Scleral inflammation ranging from +1 to +3 as assessed by central reading center based on standardized scleritis grading scale.
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- and:
- are receiving no other treatment; or,
- are receiving prednisone (or equivalent dose of another corticosteroid) and/or at least 1 other systemic immunosuppressant;
- Have anterior scleritis.
- Sufficient inflammation to require systemic treatment or long-term regional treatment.
- Subjects whom the investigators feel may only need short-term topical therapy should not be enrolled.
- Best-corrected visual acuity (ETDRS method) of 20/20 to 20/400 in the study eye;
- Best- corrected visual acuity (ETDRS method) of 20/400 or better in the fellow eye
- Must have a chest radiograph within 3 months prior to enrollment with no evidence of malignancy, infection or fibrosis.
- Females of childbearing potential must have a negative urine pregnancy test at screening. In addition, sexually active females of childbearing potential must agree to use TWO of the following adequate forms of contraception while on study medication: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner.
- Males must agree to use barrier contraception (latex condoms) when engaging in sexual activity while on study medication and for 28 days after taking the last dose of study medication.
- Prior to study screening, potential subjects must have been evaluated and screened for infectious etiologies by the investigators, possibly as part of standard clinical acre; all testing to rule out infectious causes must be performed within 3 months of screening for the ATLAS study.
- Currently active and uncontrolled scleritis, that at the determination of the investigator, requires the initiation of corticosteroid monotherapy (or equivalent), or prednisone therapy and immunomodulatory therapy or injections of corticosteroid (periocular); or scleritis in subjects for whom oral corticosteroid is contraindicated, relatively or absolutely.
- Evidence of active non-infectious scleral inflammation that at the determination of investigator requires therapy. Such evidence can be documented by clinical examination, photography, or ancillary testing (e.g. B-scan ultrasonography, fluorescein angiography, optical coherence tomography). As long as the investigator determines that the degree of inflammation can be monitored for regression or progression, the inflammation criterion can be met.
- Not planning to undergo elective ocular surgery during the first 6 months of the study.
- Subjects who have developed scleritis as ocular manifestation of an underlying systemic disease can be enrolled in the study only if the systemic therapy will not be altered throughout the study span. If at any point during the study, the ongoing systemic therapy needs to be altered (e.g. increase in the dose), the subject will have to exit the study.
- If scleritis is the initial manifestation of an underlying systemic disease, and the subjects need to be started on systemic therapy in the form of corticosteroids or immunomodulatory therapy for the underlying disease, then the subjects will not be eligible to participate in the study.
- Subjects with any or all of the following ocular complications associated with or secondary to scleritis may also be eligible for enrollment:
- Evidence of active anterior uveitis (defined as +1 cells or more in the anterior chamber or evidence of anterior vitreous inflammation on slit-lamp examination at presentation).
- Ocular hypertension, defined as intraocular pressure of ≥ 21 mmHg.
- Peripheral keratitis; defined as peripheral interstitial keratitis or thinning with either ulcerative or non-ulcerative component.10
- Subjects who have been on immunomodulatory therapy (IMT) prior to enrollment may participate in the study if they have been on a stable dose of IMT (at least 4 weeks with no change in IMT dosing or addition of new IMT agents).
Who cannot join
- Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:
- Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision.
- Age-related macular degeneration;
- Myopic degeneration with active subfoveal choroidal neovascularization.
- Advanced glaucoma status post trabeculectomy or tube/valve placement
- Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:
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- Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors);
- Posterior subtenon's steroids.
- Intraocular surgery within 90 days prior to Day 0 in the study eye;
- Capsulotomy within 30 days prior to Day 0 in the study eye;
- Any known ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following Day 0;
- Presence of posterior scleritis as the only type of scleritis (without concurrent presence of any type of anterior scleritis;
- Intraocular pressure ≥25 mmHg in the study eye (glaucoma subjects maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate);
- Pupillary dilation inadequate for quality stereoscopic fundus photography in the study eye;
- Media opacity that would limit clinical visualization;
- Presence of any form of ocular malignancy in the study eye, including choroidal melanoma;
- History of herpetic infection in the study eye or adnexa;
- Presence of known active or inactive toxoplasmosis in either eye;
- Presence of ocular or periocular infection in either eye;
- Participation in other investigational drug or device clinical trials within 30 days prior to Day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following Day 0. This includes both ocular and non-ocular clinical trials.
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
- Prior treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti¬CD3, anti-CD19 and anti- CD20.
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
- Previous treatment with ACTH within 3 months of day 0 of study visit.
- Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
- Exclusions for General Safety:
- History of severe allergic or anaphylactic reactions to proteins of porcine origin.
- Evidence of serious uncontrolled concomitant cardiovascular (including history of congestive heart failure, uncontrolled hypertension), nervous system (include myasthenia gravis), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (includeAdrenocortical hyperfunction and primary adrenocortical insufficiency, uncontrolled diabetes mellitus, hypothyroidism), gastrointestinal disease (including history of or presence peptic ulcer disease, complicated diverticulitis, ulcerative colitis, or Crohn's disease), Scleroderma or Osteoporosis.
- Current liver disease as determined by principal investigator unless related to primary disease under investigation.
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
- Active TB requiring treatment within the previous 3 years. Subjects should be evaluated for latent and/or active TB within one month of the screening as part of the evaluation by the investigator to rule out infectious scleritis or uveitis before referring the patient to the study. If positive, subjects should be managed following local practice guidelines prior to initiating ACTH Gel. Subjects treated for TB with no recurrence in 3 years are permitted.
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of active malignant disease, malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured).
- Pregnant women or nursing (breast-feeding) mothers.
- Subjects with reproductive potential not willing to use an effective method of contraception.
- History of alcohol, drug or chemical abuse within 1 year prior to screening.
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
- Laboratory Exclusion Criteria (at screening):
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times upper limit of normal (ULN)
- Total Bilirubin> 2 times ULN
- HbA1c > 10.0 %
- White Blood Cells < 3.0 x 109/L (3000/mm3)
- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
- TSH > 4U/ml or greater than normal cut-off for the lab conducting the test
- BMD (Bone Mineral Density) < -2.5 T score
Trial locations and contacts
3 sites in 1 country.
Atlas Study contact
United States3 sites, 3 recruiting
- Recruiting
Metropolitan Eye Research and Surgery Institute
Palisades Park, New Jersey, 07650
David S Chu, MD, uveitisnj@gmail.com
Yael Sharon, MD, yael@mersieye.com
- Recruiting
Byers Eye Institute, Stanford University
Palo Alto, California, 94303
Quan D Nguyen, MD, MSc
- Recruiting
Foresight Studies, LLC
San Antonio, Texas, 78240
David K Scales, MD
About this study
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
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.
Read more
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.
H.P. 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.
Read the 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 myoclonus,dermatomyositis and polymyositis. These reports also include cases that were resistant to steroids and other immunomodulatory drugs, supporting the immune-modulating properties of ACTH. H.P. 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 (1:1) 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 mg/kg 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 BL/Visit 2. Steroid dose will be tapered from BL/Visit 2 onwards until week 9 (Visit 5). If the scleritis is still greater than 0.5+ 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:
- Mandatory 80 U twice weekly treatment with SC ACTH gel, starting at the Baseline visit (Day 0) until end of week 16.
- 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:
- No evidence of active disease/disease resolved - treatment dose will be reduced to 80 U once a week with SC ACTH gel.
- Evidence of disease improvement, but still active/partial 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.
- No evidence of improvement/disease 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.
- Conditions
- Scleritis
- Being tested
- ACTH (adrenocorticotropic hormone) gel
- Keywords
- Scleritis, anterior, adrenocorticotropic hormone, ACTH, Non-infectious
- Medical subject headings
- Scleritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACTH (adrenocorticotropic hormone) gelDrug
Also called H.P. Acthar® Gel
The dose of H.P. Acthar Gel is 80 Units administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Twice Weekly Treatment Arm | Experimental | Patients in this treatment arm will receive mandatory 80 U twice weekly treatment with SC ACTH (adrenocorticotropic hormone) gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 17, the treatment will be administered on as needed basis, based on the retreatment criteria. Receives: Drug: ACTH (adrenocorticotropic hormone) gel |
| Thrice Weekly Treatment Arm | Experimental | Patients in this treatment arm will receive mandatory 80 U thrice weekly treatment with SC ACTH (adrenocorticotropic hormone) gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 16, the treatment will be administered on as needed basis, based on the retreatment criteria. Receives: Drug: ACTH (adrenocorticotropic hormone) gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in grade of pain on an 11-point pain intensity numerical rating scale (NRS).
The proportion of subjects demonstrating improvement (mean change from BL) by 5 points in pain, graded on an 11-point pain intensity numerical rating scale (NRS).
Measured: At the primary end point (week 16) and at the end of follow-up period (week 52) or at time of rescue
Change in degree of inflammation, based on the standardized scleritis grading scale.
The proportion of subjects demonstrating improvement (mean change from BL) in inflammation (equal to or less than +0.5), based on the standardized scleritis grading scale.
Measured: At the primary end point (week 16) and at the end of follow-up period (week 52) or at time of rescue
Secondary outcomes (7)
Best corrected visual acuity outcome
Mean change from Baseline (BL) in BCVA by ≥ 10 letters or 2 lines using the ETDRS method and at week 16 and week 52 after therapy or at time of rescue.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Vascular leakage outcome
Changes in degree of leakage on fluorescein angiogram (as assessed by centralized reading center) of the optic nerve and/or retinal vasculature from Baseline (BL) through week 16 and week 52.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Retinal thickness outcome
Changes in retinal thickness as demonstrated by spectral-domain optical coherence tomography (OCT), as assessed by the centralized reading center, for subjects with macular edema from Baseline (BL) through week 16 and week 52.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Scleral thickness outcome
Changes in scleral thickness as demonstrated by spectral-domain optical coherence tomography (OCT), as assessed by the centralized reading center, from Baseline (BL) through week 16 and week 52.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Dosage of systemic corticosteroids outcome
Changes in the dosage of systemic corticosteroids from Baseline (BL) through week 16 and week 52.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Response to therapy with/without systemic corticosteroids
Proportion of subjects successfully weaned off of steroids by the primary end point.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Changes in steroids dosage during study
Mean change in the dose of steroids from BL to primary end point and from BL to week 52.
Measured: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start1 Jan 2019
- Primary completion8 Dec 2024 (estimated)
- Study completion8 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for ScleritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model 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. Thirty (30) subjects with non-infectious anterior scleritis will be enrolled and randomized (1:1) at their first visit to one of the two treatment arms: 1. Mandatory 80 U twice weekly treatment with SC ACTH gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 17, the treatment will be administered on as needed basis, based on the retreatment criteria. 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, the treatment will be administered on as needed basis, based on the retreatment criteria.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Metropolitan Eye Research & Surgery Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt, Stanford University, Ocular Imaging Research and Reading Center, Foresight Studies, LLC
- Responsible party
- Sponsor
- Investigators
- David S. Chu, MD, Principal investigator, Metropolitan Eye Research and Surgery InstituteQuan D Nguyen, MD, MSc, Principal investigator, Stanford UniversityDavid K Scales, MD, Principal investigator, Foresight Studies, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03465111
- Sponsor's protocol ID
- #4301
- Acronym
- ATLAS
- Status last verified
- Oct 2023
- First submitted
- 16 Feb 2018
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. Surv Ophthalmol. 2005 Jul-Aug;50(4):351-63. doi: 10.1016/j.survophthal.2005.04.001.
PubMed 15967190Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Ophthalmology. 1994 Feb;101(2):389-96. doi: 10.1016/s0161-6420(94)31325-x.
PubMed 8115160Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan;119(1):43-50. doi: 10.1016/j.ophtha.2011.07.013. Epub 2011 Oct 2.
PubMed 21963265Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004 Mar;111(3):501-6. doi: 10.1016/j.ophtha.2003.06.006.
PubMed 15019326Keino H, Watanabe T, Taki W, Nakashima C, Okada AA. Clinical features and visual outcomes of Japanese patients with scleritis. Br J Ophthalmol. 2010 Nov;94(11):1459-63. doi: 10.1136/bjo.2009.171744. Epub 2010 Jun 24.
PubMed 20576778Erkanli L, Akova YA, Guney-Tefekli E, Tugal-Tutkun I. Clinical features, prognosis, and treatment results of patients with scleritis from 2 tertiary eye care centers in Turkey. Cornea. 2010 Jan;29(1):26-33. doi: 10.1097/ICO.0b013e3181ac9fad.
PubMed 19907295Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with systemic vasculitic diseases. Ophthalmology. 1995 Apr;102(4):687-92. doi: 10.1016/s0161-6420(95)30970-0.
PubMed 7724185Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a community-based referral practice. Am J Ophthalmol. 2009 Dec;148(6):946-50. doi: 10.1016/j.ajo.2009.07.021. Epub 2009 Oct 17.
PubMed 19837380Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163-91. doi: 10.1136/bjo.60.3.163.
PubMed 1268179Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469-76. doi: 10.1016/s0002-9394(00)00710-8.
PubMed 11024419Kolomeyer AM, Ragam A, Shah K, Do BK, Shah VP, Chu DS. Cyclo-oxygenase inhibitors in the treatment of chronic non-infectious, non-necrotizing scleritis and episcleritis. Ocul Immunol Inflamm. 2012 Aug;20(4):293-9. doi: 10.3109/09273948.2012.689075. Epub 2012 May 29.
PubMed 22642498Ragam A, Kolomeyer AM, Fang C, Xu Y, Chu DS. Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis factor alpha inhibitors. Ocul Immunol Inflamm. 2014 Dec;22(6):469-77. doi: 10.3109/09273948.2013.863944. Epub 2013 Dec 19.
PubMed 24354512Jachens AW, Chu DS. Retrospective review of methotrexate therapy in the treatment of chronic, noninfectious, nonnecrotizing scleritis. Am J Ophthalmol. 2008 Mar;145(3):487-492. doi: 10.1016/j.ajo.2007.11.010.
PubMed 18282493Kolomeyer AM, Ragam A, Shah K, Jachens AW, Tu Y, Chu DS. Mycophenolate mofetil in the treatment of chronic non-infectious, non-necrotizing scleritis. Ocul Immunol Inflamm. 2012 Apr;20(2):113-8. doi: 10.3109/09273948.2012.655398.
PubMed 22409564Star RA, Rajora N, Huang J, Stock RC, Catania A, Lipton JM. Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8016-20. doi: 10.1073/pnas.92.17.8016.
PubMed 7544012
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03465111
- Acronym / sponsor ID
- ATLAS / #4301
- Conditions
- Scleritis
- Keywords
- Scleritis, anterior, adrenocorticotropic hormone, ACTH, Non-infectious
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Metropolitan Eye Research & Surgery InstituteUniversity, hospital or other
- Collaborators
- Mallinckrodt, Stanford University, Ocular Imaging Research and Reading Center, Foresight Studies, LLC
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 8 Dec 2024 (estimated)
- Study completion
- 8 Dec 2024 (estimated)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
H.P. 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 myoclonus,dermatomyositis and polymyositis. These reports also include cases that were resistant to steroids and other immunomodulatory drugs, supporting the immune-modulating properties of ACTH. H.P. 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 (1:1) 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 mg/kg 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 BL/Visit 2. Steroid dose will be tapered from BL/Visit 2 onwards until week 9 (Visit 5). If the scleritis is still greater than 0.5+ 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:
- Mandatory 80 U twice weekly treatment with SC ACTH gel, starting at the Baseline visit (Day 0) until end of week 16.
- 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:
- No evidence of active disease/disease resolved - treatment dose will be reduced to 80 U once a week with SC ACTH gel.
- Evidence of disease improvement, but still active/partial 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.
- No evidence of improvement/disease 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model 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. Thirty (30) subjects with non-infectious anterior scleritis will be enrolled and randomized (1:1) at their first visit to one of the two treatment arms: 1. Mandatory 80 U twice weekly treatment with SC ACTH gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 17, the treatment will be administered on as needed basis, based on the retreatment criteria. 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, the treatment will be administered on as needed basis, based on the retreatment criteria.
| Arm | Type | Receives |
|---|---|---|
| Twice Weekly Treatment Arm | Experimental | Drug: ACTH (adrenocorticotropic hormone) gelPatients in this treatment arm will receive mandatory 80 U twice weekly treatment with SC ACTH (adrenocorticotropic hormone) gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 17, the treatment will be administered on as needed basis, based on the retreatment criteria. |
| Thrice Weekly Treatment Arm | Experimental | Drug: ACTH (adrenocorticotropic hormone) gelPatients in this treatment arm will receive mandatory 80 U thrice weekly treatment with SC ACTH (adrenocorticotropic hormone) gel, starting at the Baseline visit (Day 0) until end of week 16. Starting at week 16, the treatment will be administered on as needed basis, based on the retreatment criteria. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Adults, age ≥ 18 years;
- Able to give informed consent and attend all study visits;
- Have diagnosis of non-necrotizing scleritis determined by the Investigator to be non-infectious;
- Have active scleirits, defined as:
- Characteristic clinical presentation of active disease: painful inflammation, edema and tenderness to touch radiating to the forehead, the brow, the jaw, or the sinuses. Severity of pain associated with scleritis will be based on pain intensity, NRS scale.
Key exclusion criteria (48 listed)
- Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:
- Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:
- Intraocular surgery within 90 days prior to Day 0 in the study eye;
- Capsulotomy within 30 days prior to Day 0 in the study eye;
- Any known ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following Day 0;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACTH (adrenocorticotropic hormone) gelAlso: H.P. Acthar® GelThe dose of H.P. Acthar Gel is 80 Units administered subcutaneously | Drug | Thrice Weekly Treatment Arm, Twice Weekly Treatment Arm |
Primary outcome
Change in grade of pain on an 11-point pain intensity numerical rating scale (NRS).
Time frame: At the primary end point (week 16) and at the end of follow-up period (week 52) or at time of rescue
The proportion of subjects demonstrating improvement (mean change from BL) by 5 points in pain, graded on an 11-point pain intensity numerical rating scale (NRS).
Change in degree of inflammation, based on the standardized scleritis grading scale.
Time frame: At the primary end point (week 16) and at the end of follow-up period (week 52) or at time of rescue
The proportion of subjects demonstrating improvement (mean change from BL) in inflammation (equal to or less than +0.5), based on the standardized scleritis grading scale.
7 secondary outcomes
Best corrected visual acuity outcome
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Vascular leakage outcome
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Retinal thickness outcome
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Scleral thickness outcome
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Dosage of systemic corticosteroids outcome
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Response to therapy with/without systemic corticosteroids
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Changes in steroids dosage during study
Time frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Background: PubMed 15967190Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. Surv Ophthalmol. 2005 Jul-Aug;50(4):351-63. doi: 10.1016/j.survophthal.2005.04.001.
- Background: PubMed 8115160Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Ophthalmology. 1994 Feb;101(2):389-96. doi: 10.1016/s0161-6420(94)31325-x.
- Background: PubMed 21963265Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan;119(1):43-50. doi: 10.1016/j.ophtha.2011.07.013. Epub 2011 Oct 2.
- Background: PubMed 15019326Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004 Mar;111(3):501-6. doi: 10.1016/j.ophtha.2003.06.006.
- Background: PubMed 20576778Keino H, Watanabe T, Taki W, Nakashima C, Okada AA. Clinical features and visual outcomes of Japanese patients with scleritis. Br J Ophthalmol. 2010 Nov;94(11):1459-63. doi: 10.1136/bjo.2009.171744. Epub 2010 Jun 24.
- Background: PubMed 19907295Erkanli L, Akova YA, Guney-Tefekli E, Tugal-Tutkun I. Clinical features, prognosis, and treatment results of patients with scleritis from 2 tertiary eye care centers in Turkey. Cornea. 2010 Jan;29(1):26-33. doi: 10.1097/ICO.0b013e3181ac9fad.
- Background: PubMed 7724185Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with systemic vasculitic diseases. Ophthalmology. 1995 Apr;102(4):687-92. doi: 10.1016/s0161-6420(95)30970-0.
- Background: PubMed 19837380Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a community-based referral practice. Am J Ophthalmol. 2009 Dec;148(6):946-50. doi: 10.1016/j.ajo.2009.07.021. Epub 2009 Oct 17.
- Background: PubMed 1268179Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163-91. doi: 10.1136/bjo.60.3.163.
- Background: PubMed 11024419Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469-76. doi: 10.1016/s0002-9394(00)00710-8.
- Background: PubMed 22642498Kolomeyer AM, Ragam A, Shah K, Do BK, Shah VP, Chu DS. Cyclo-oxygenase inhibitors in the treatment of chronic non-infectious, non-necrotizing scleritis and episcleritis. Ocul Immunol Inflamm. 2012 Aug;20(4):293-9. doi: 10.3109/09273948.2012.689075. Epub 2012 May 29.
- Background: PubMed 24354512Ragam A, Kolomeyer AM, Fang C, Xu Y, Chu DS. Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis factor alpha inhibitors. Ocul Immunol Inflamm. 2014 Dec;22(6):469-77. doi: 10.3109/09273948.2013.863944. Epub 2013 Dec 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Atlas Study contact
David S. Chu, MD principal investigator
Metropolitan Eye Research and Surgery Institute
Quan D Nguyen, MD, MSc principal investigator
Stanford University
David K Scales, MD principal investigator
Foresight Studies, LLC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACTH (adrenocorticotropic hormone) gel in people with Scleritis, run by Metropolitan Eye Research & Surgery Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact David S. Chu, MD (888-823-8808, uveitisnj@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in grade of pain on an 11-point pain intensity numerical rating scale (NRS). (time frame: At the primary end point (week 16) and at the end of follow-up period (week 52) or at time of rescue). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03465111, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.