ACTHAR Therapy for Central Nervous System Sarcoidosis

There is a need for a more reliable, expeditious therapy that can be used as an alternative to glucocorticoids in severe Central Nervous System (CNS) sarcoidosis. This study aims to provide evidence for effectiveness of ACTHAR gel in CNS sarcoidosis, and provide information about its safety and tolerability

Study Overview

• Status: Withdrawn
• Conditions: Sarcoidosis
• Intervention / Treatment: Drug: Repository Corticotropin Injection

Detailed Description

Central nervous system (CNS) involvement is one of the most severe manifestations of sarcoidosis. Sarcoidosis affecting the leptomeninges, spinal cord, or brain parenchyma portends a difficult course and frequently results in severe disability or death (1). Treatment of moderate and severe CNS sarcoidosis typically involves a combination of corticosteroids and cytotoxic agents such as methotrexate (2). Unfortunately, most response rates are reportedly only in the 29-38% range for corticosteroids alone, and the effects of cytotoxic agents in sarcoidosis require up to 6 months to occur. A typical scenario is that patients are treated for prolonged periods with high dose glucocorticoids with suboptimal effectiveness despite development of substantial toxicities. Some series report that cyclophosphamide or infliximab may be beneficial (3), but these approaches are limited by potentially severe toxicities, loss of effectiveness, or payor constraints.

. 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
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with sarcoidosis as defined by ATS/ERS/WASOG (American Thoracic Society/European Thoracic Society/World Association for Sarcoidosis and Other Granulomatous Disorders)
• Stable baseline immunosuppressive medications

• Moderate to severe disease as defined by at least one of the following criteria:

  • Cranial nerve palsy
  • Neurologic deficits related to intraparenchymal brain, spinal cord and/or cauda equina involvement
  • Dural or leptomeningeal involvement of brain and/or spinal cord
  • Hydrocephalus
  • Seizures

Exclusion Criteria:

• Diagnosis of any underlying neurologic disorder that would potentially confound interpretation of the study results
• Significant change in corticosteroid dose within the past 4 weeks, or other immunosuppressive medication within the past 6 months
• Evidence of current serious infection, or a history of chronic or recurring infections.
• Contraindication to high-dose corticosteroids (e.g. uncontrolled blood sugar).
• Allergies to pig-derived proteins
• Have a history of any opportunistic infection within 6 months prior to screening
• History of malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 48 weeks on therapy.	Drug: Repository Corticotropin Injection; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with clinically significant improvement - successful glucocorticoid tapering.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with clinically significant improvement - no need for escalation of other therapy.	12 Weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): November 2, 2020
• Study Completion (Actual): November 2, 2020

Study Registration Dates

• First Submitted: September 29, 2016
• First Submitted That Met QC Criteria: September 29, 2016
• First Posted (Estimate): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: ACTHAR CNS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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