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A Clinical Study to Evaluate the Potential Role of ACTH Gel in Patients With Scleritis (ATLAS)

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ClinicalTrials.gov Identifier: NCT03465111
Recruitment Status : Not yet recruiting
First Posted : March 14, 2018
Last Update Posted : August 16, 2018
Sponsor:
Collaborators:
Mallinckrodt
Stanford University
Ocular Imaging Research and Reading Center
Colorado Retina Associates
Texas Retina Associates
University of Louisville
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Metropolitan Eye Research & Surgery Institute

Brief Summary:

ATLAS study is a clinical trial to evaluate the potential role of subcutaneous adrenocorticotropic hormone (ACTH) gel, in the management of 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. The patients will be randomized (1:1) at their first visit to one of the two treatment arms: Twice-weekly or thrice-weekly SC administration of 80 Units of ACTH Gel. The effect of two dose regimens of subcutaneous ACTH gel in patients with scleritis will be monitored and evaluated.

Patients enrolling to the study include those with non-infectious scleritis, which is an inflammatory disease affecting the sclera (white outer coating of the eye) and cause blurring of vision, redness, tearing and painful ocular inflammatory episodes in one or both eyes. Scleritis may results in vision threatening ocular complications (corneal ulceration, cataract, glaucoma, retinal detachment) and subsequent blindness, if left untreated. Treatment of scleritis is usually chronic and requires systemic therapy with non-steroidal anti-inflammatory drugs and corticosteroids, along with immunosuppression 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. ACTH stimulates the adrenal cortex gland to secrete cortisol, corticosterone, and aldosterone. It is FDA approved treatment for flares or on a regular basis (maintenance) in people with systemic lupus erythematosus (lupus), infantile spasms in infants and children under 2 years of age, 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 in patients with scleritis.


Condition or disease Intervention/treatment Phase
Scleritis Drug: ACTH (adrenocorticotropic hormone) gel Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Estimated Study Start Date : September 15, 2018
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Twice Weekly Treatment Arm
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.
Drug: ACTH (adrenocorticotropic hormone) gel
The dose of H.P. Acthar Gel is 80U administered subcutaneously either twice or thrice weekly. H.P. Acthar Gel (repository corticotropin injection) is supplied as 5 mL multi-dose vial containing 80 USP Units per mL. Subjects will utilize two vials per week or three vials per week depending on the group they are assigned to.
Other Name: H.P. Acthar® Gel

Experimental: Thrice Weekly Treatment Arm
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.
Drug: ACTH (adrenocorticotropic hormone) gel
The dose of H.P. Acthar Gel is 80U administered subcutaneously either twice or thrice weekly. H.P. Acthar Gel (repository corticotropin injection) is supplied as 5 mL multi-dose vial containing 80 USP Units per mL. Subjects will utilize two vials per week or three vials per week depending on the group they are assigned to.
Other Name: H.P. Acthar® Gel




Primary Outcome Measures :
  1. 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 from Base line (BL) in clinical features of scleritis, and at week 16 and week 52 after therapy or at time of rescue:

    • Improvement (mean change from BL) by 5 points in pain, graded on an 11-point pain intensity numerical rating scale (NRS).


  2. 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 from Base line (BL) in clinical features of scleritis, and at week 16 and week 52 after therapy or at time of rescue:

    • Improvement (mean change from BL) in inflammation (equal to or less than +0.5), based on the standardized scleritis grading scale.



Secondary Outcome Measures :
  1. Best corrected visual acuity outcome [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    Best corrected visual acuity (BCVA): 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.

  2. Vascular leakage outcome [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    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.

  3. Retinal thickness outcome [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    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.

  4. Scleral thickness outcome [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    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.

  5. Dosage of systemic corticosteroids outcome [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    Changes in the dosage of systemic corticosteroids from Baseline (BL) through week 16 and week 52.

  6. Response to therapy with/without systemic corticosteroids [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    Proportion of subjects successfully weaned off of steroids by the primary end point.

  7. Changes in steroids dosage during study [ Time Frame: At week 16 (primary end point) and week 52 (end of follow-up) after therapy ]
    Mean change in the dose of steroids from BL to primary end point and from BL to week 52.


Other Outcome Measures:
  1. Incidence and severity of ocular adverse events (AEs) [ Time Frame: At Baseline (BL) and monthly visits after screening ]
    The incidence and severity of ocular adverse events (AEs), as identified by eye examination (including BCVA testing), slit lamp biomicroscopy, optical coherence tomography OCT (anterior and posterior), anterior segment photography, fundus photography (FP) and fluorescein angiography (FA).

  2. Incidence and severity of other AEs [ Time Frame: At Baseline (BL) and monthly visits after screening ]
    The incidence and severity of other AEs, as identified by physical examinations, changes in vital signs, weight, clinical laboratory abnormalities, Electrocardiography (ECG) findings and subject reporting.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

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).

Exclusion Criteria:

  • 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:

    • 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) > 1.5 times upper limit of normal (ULN)
  • Total Bilirubin>ULN
  • HbA1c > 8.0 %
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03465111


Contacts
Contact: David S. Chu, MD 888-823-8808 uveitisnj@gmail.com
Contact: Atlas Study atlasstudy@oirrc.net

Locations
United States, New Jersey
Metropolitan Eye Research and Surgery Institute Not yet recruiting
Palisades Park, New Jersey, United States, 07650
Contact: David S Chu, MD       uveitisnj@gmail.com   
Contact: Yael Sharon, MD       yael@mersieye.com   
Sponsors and Collaborators
Metropolitan Eye Research & Surgery Institute
Mallinckrodt
Stanford University
Ocular Imaging Research and Reading Center
Colorado Retina Associates
Texas Retina Associates
University of Louisville
Weill Medical College of Cornell University
Investigators
Principal Investigator: David S. Chu, MD Metropolitan Eye Research and Surgery Institute
Principal Investigator: Quan D Nguyen, MD, MSc Stanford University
Principal Investigator: Robert Wang, MD Texas Retina Associates
Principal Investigator: Mark S Dacey, MD Colorado Retina Institute
Principal Investigator: Henry Kaplan, MD University of Louisville
Principal Investigator: Kimberley Sippel, MD Weill Cornell Ophthalmology

Publications:

Responsible Party: Metropolitan Eye Research & Surgery Institute
ClinicalTrials.gov Identifier: NCT03465111     History of Changes
Other Study ID Numbers: #4301
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Metropolitan Eye Research & Surgery Institute:
Scleritis
anterior
adrenocorticotropic hormone
ACTH
Non-infectious

Additional relevant MeSH terms:
Scleritis
Scleral Diseases
Eye Diseases
Hormones
Adrenocorticotropic Hormone
Melanocyte-Stimulating Hormones
beta-Endorphin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action