Treatment of CNS Sarcoidosis With H.P. Acthar Gel

Clinical Biomarkers of Disease Activity and Treatment Responses in Patients With CNS Sarcoidosis Treated With H.P. Acthar Gel

The purpose of this study is to see if treatment with H.P. Acthar® Gel will result in the improvement and long-term stabilization of clinical and radiographic abnormalities that occur in patients with CNS sarcoidosis. In addition, it will also look at whether treatment will be also associated with improvement in measures of quality of life. The treatment of CNS sarcoidosis involves the use of either corticosteroids such as prednisone or potent immunosuppressive agents such as methotrexate, both which can induce severe long term side effects. The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel. The efficacies of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously studied. In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment.

Study Overview

• Status: Completed
• Conditions: CNS Sarcoidosis
• Intervention / Treatment: Drug: H.P. Acthar Gel

Detailed Description

Sarcoidosis is a chronic and frequently progressive systemic disease that affects the central nervous system (CNS) in approximately 5% of patients. The hallmark of the disease is the development of chronic inflammation with formation of non-caseating granulomas that can involve the brain parenchyma and meninges and appear as contrast-enhancing mass lesions on magnetic resonance imaging. The granulomas are primarily comprised of proinflammatory T cells (Th1 cells and Th17 cells) and macrophages which accumulate during the early stages of granuloma formation. The inflammation that is generated by these cells is modulated by anti-inflammatory responses mediated by Th2 cells and regulatory T (Treg) cells that later appear and populate the outer regions of the granuloma. The presence of Treg cells are of particular interest since these cell are also detected in high numbers in peripheral blood and the immune suppression that results may underlie the occurrence of anergy in patients with the disease. The treatment of CNS sarcoidosis involves the use of either corticosteroids or potent immunosuppressive agents, both which can induce severe long-term side effects. The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel. The efficacy of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously examined. In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment. These issues, therefore, will be explored in the context of this proposal.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A highly probable diagnosis of sarcoidosis, as determined using the World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG) Sarcoidosis Organ Assessment Instrument (Judson et al., 2014), with involvement not limited to the central nervous system.
• At the time of enrollment, a history of clinical deterioration based on the development of new symptoms or worsening previously present symptoms with confirmation by clinical examination and objective clinical testing.
• If on steroids, on a stable dose of the medication for at least 3 months.

Exclusion Criteria:

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. Acthar Gel; Participants will receive active treatment with H.P. Acthar Gel	Drug: H.P. Acthar Gel; 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12; Other Names: ACTH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Karnofsky Performance Status (KPS) Score	The Karnofsky Performance Scale score allows patients to be classified as to their functional impairment. This can be used to compare the effectiveness of different therapies and to assess the prognosis in individual patients. The scale ranges from 0 to 100. Higher scores are associated with better outcomes.	12 months (intention to treat)
Change in Total Number of New Lesions	Change in the total number of lesions assessed at 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Determined Disease Steps (PDDS)	A patient-reported measure of disability which consists of a scale with 9 levels of disability ranging from 0 to 8 (higher scores are associated with worse disability).	12 months (intention to treat)
Montreal Cognitive Assessment (MoCA)	The MoCA is a 30-point test that screens for cognitive impairment. Scores range from 0 to 30, with higher scores associated with a better outcome.	12 months
Symbol-Digit Modalities Test (SDMT)	Assesses cognitive function. The patient is given a set of symbols, and each symbol is paired with a number. The patient is given 90 seconds to write down the number that corresponds to each symbol.Scores range from 0 to 110. A higher score is associated with a better outcome.	12 months (intention to treat)
Work Productivity and Activities Impairment -General Health (WPAI-GH)	The WPAI-GH consists of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed for other reasons; 4 = hours actually worked; 5 = degree that the patient's health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6 = degree health affected productivity in regular unpaid activities (VAS). The result for question 5 is used for the outcome measure, for which a higher number is associated with a worse outcome.	12 months (intention to treat)
Beck Depression Inventory	The Beck Depression Inventory measures the severity of depression in adolescents and adults. It consists of 21 subscales, and the score for each individual subscale is added to give a total score of between 0 to 63. Total scores <= 10 are considered normal. Scores > 10 are considered abnormal, with higher scores above that cutoff being associated with a worse outcome.	12 months (intent to treat)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum and Cerebrospinal Fluid Immune Markers	Change in levels of serum and cerebrospinal fluid immune markers at 4 weeks, 6 months and 12 months versus baseline	4 weeks, 6 months and 12 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Horea Rus, University of Maryland, Baltimore

Publications and helpful links

General Publications

• Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med. 2002 Sep;8(5):435-40. doi: 10.1097/00063198-200209000-00016.
• Arnason BG, Berkovich R, Catania A, Lisak RP, Zaidi M. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013 Feb;19(2):130-6. doi: 10.1177/1352458512458844. Epub 2012 Oct 3.
• Co DO, Hogan LH, Il-Kim S, Sandor M. T cell contributions to the different phases of granuloma formation. Immunol Lett. 2004 Mar 29;92(1-2):135-42. doi: 10.1016/j.imlet.2003.11.023.
• Judson MA, Costabel U, Drent M, Wells A, Maier L, Koth L, Shigemitsu H, Culver DA, Gelfand J, Valeyre D, Sweiss N, Crouser E, Morgenthau AS, Lower EE, Azuma A, Ishihara M, Morimoto S, Tetsuo Yamaguchi T, Shijubo N, Grutters JC, Rosenbach M, Li HP, Rottoli P, Inoue Y, Prasse A, Baughman RP, Organ Assessment Instrument Investigators TW. The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis. 2014 Apr 18;31(1):19-27.
• Miller DH, Kendall BE, Barter S, Johnson G, MacManus DG, Logsdail SJ, Ormerod IE, McDonald WI. Magnetic resonance imaging in central nervous system sarcoidosis. Neurology. 1988 Mar;38(3):378-83. doi: 10.1212/wnl.38.3.378.
• Moller DR. Treatment of sarcoidosis -- from a basic science point of view. J Intern Med. 2003 Jan;253(1):31-40. doi: 10.1046/j.1365-2796.2003.01075.x.
• Royal W 3rd, Mia Y, Li H, Naunton K. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol. 2009 Aug 18;213(1-2):135-41. doi: 10.1016/j.jneuroim.2009.05.012. Epub 2009 Jun 17.
• Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011 Oct 10;11(11):762-74. doi: 10.1038/nri3070.
• Stern BJ, Aksamit A, Clifford D, Scott TF; Neurosarcoidosis Study Group. Neurologic presentations of sarcoidosis. Neurol Clin. 2010 Feb;28(1):185-98. doi: 10.1016/j.ncl.2009.09.012.
• Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol. 1985 Sep;42(9):909-17. doi: 10.1001/archneur.1985.04060080095022.
• Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Kambouchner M, Valeyre D, Chapelon-Abric C, Debre P, Piette JC, Gorochov G. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006 Feb 20;203(2):359-70. doi: 10.1084/jem.20050648. Epub 2006 Jan 23.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: November 14, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimated): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Pituitary Hormones; Pituitary Hormones, Anterior; Melanocortins; Pro-Opiomelanocortin; Adrenocorticotropic Hormone
• Other Study ID Numbers: HP-00062490

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No