Ocular Sarcoidosis Open Label Trial of ACTHAR Gel

Treatment with ACTHAR Gel will result in a reduction of ocular inflammation in patients with active ocular sarcoidosis that requires systemic immunosuppressant therapy (hypothesis)

Study Overview

• Status: Completed
• Conditions: Panuveitis; Anterior Uveitis; Ocular Sarcoidosis
• Intervention / Treatment: Drug: Repository Corticotropin Injection; Drug: Repository Corticotropin Injection -Treatment Extension

Detailed Description

The initial treatment of ocular sarcoidosis usually relies on a combination of topical glucocorticoids and oral glucocorticoids, both of which are associated with significant ocular and systemic toxicities. Steroid-sparing therapies are limited by variable and unpredictable efficacy, prolonged time until clinical response, medication intolerance, and difficulties obtaining payor approval. As a result, it is not uncommon that treating physicians must choose between excessive glucocorticoid toxicity versus poor control of ocular inflammation. Ongoing ocular inflammation, in turn, leads to eventual visual loss and occasionally blindness.

There is a need for a more reliable, expeditious therapy that can be used as an alternative to glucocorticoids in sarcoidosis uveitis. Adrenocorticotropic hormone, through activation of melanocortin receptors on leukocytes, can dampen immune responses through non-glucocorticoid dependent mechanisms. The proposed study will aim to define whether there is effectiveness for ACTHAR gel in these patients, delineate an effect dosing regimen, and provide information about the safety of this approach for moderate to severe ocular sarcoidosis.

ACTHAR is a 39-amino acid peptide natural form of adrenocorticotropin hormone (ACTH) that was initially approved in 1952 by the FDA. It has since been approved for 19 indications including respiratory sarcoidosis, multiple sclerosis, and infantile spasms.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44145
      • Cleveland Clinical Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with sarcoidosis as defined by ATS/ERS/WASOG guidelines (American Thoracic Society/European Respiratory Society /World Association of Sarcoidosis and Other Granulomatous Diseases)
• Any posterior, intermediate or panuveitis of sufficient severity to warrant therapy, in the opinion of the treating physician --OR-- Anterior uveitis requiring 4 or more daily applications of topical corticosteroids to maintain control of inflammation, or uncontrolled with topical therapy
• Persistent disease activity (active uveitis) at the time of screening

Exclusion Criteria:

• Other cause for ocular inflammation
• Uncontrolled diabetes, hypertension, or other contra-indication to increased dosage of glucocorticoids
• Recent (less than 4 weeks) intra-ocular or intra-orbital steroid injection
• Escalation of immunosuppressive medications between screening and initiation of the study medication
• Severe extra-ocular sarcoidosis likely to require additional therapy (in the opinion of the investigator)
• Administration of an investigational medication for sarcoidosis within 3 months, or 5 half-lives, whichever is longer
• Have a history of any opportunistic infection within 6 months prior to screening
• Have any history of malignancy, except fully resected cutaneous squamous cell cancer or cutaneous basal cell cancer, or cervical carcinoma in-situ with a minimum of 5 years period without recurrence
• Severe other organ disease felt to be likely to lead to death within the next six months
• Unable to follow the study protocol, including the requisite travel and follow-up ocular testing
• Women of childbearing potential must be using adequate birth control measures (abstinence, hormonal contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must agree to continue such precautions, and not become pregnant or plan a pregnancy for 6 months after receiving their last treatment with study agent. Women of childbearing potential must test negative on a serum pregnancy test at screening.
• Breastfeeding women are excluded from participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: H.P. Achtar Gel 80 U; H.P. Acthar Gel (repository corticotropin) Injection, 80 U daily for 10 days, then 80 U twice weekly for up to a total of 24 weeks on therapy.

Drug: Repository Corticotropin Injection; Treatment with ACTHAR Gel for 24 weeks; Initial treatment with 80 units daily for ten days (induction phase); Maintenance treatment with 80 units twice weekly (maintenance phase); Other Names: ACTH; ACTH Gel; H.P. Acthar Gel; Drug: Repository Corticotropin Injection -Treatment Extension; 24 open label extension permitted in subjects who respond to treatment; Other Names: ACTH; ACTH Gel; H.P. Acthar Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Clinically Significant Improvement in Visual Acuity	The primary outcome was percentage of patients meeting at least one of the following variables 1) improved visual acuity, 2) resolution of intraocular inflammation, 3) ability to taper ocular or oral steroids by at least 50% or 4) reduction of cystoid macular edema, with no worsening of any single one and no need for additional sarcoidosis therapies at 24 weeks .	Measured at 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients Experiencing a Tapering of Ocular/Oral Steroids by at Least 50%	Measured at 24 weeks
Proportion of Patients With a Clinically Significant Reduction-cystoid Macular Edema	Measured at 24 weeks
Percentage of Patients With Clinically Significant Improvement in the Resolution-intraocular Inflammation	Measured at 24 weeks

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Daniel A Culver, DO, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: March 11, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (Estimated): March 31, 2016

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Ocular Sarcoidosis
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Eye Diseases; Uveal Diseases; Hypersensitivity; Hypersensitivity, Delayed; Iris Diseases; Uveitis; Sarcoidosis; Panuveitis; Uveitis, Anterior; Iridocyclitis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: Ocular Sarcoidosis 15-1072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO