Evaluation of the Response to Acthar Gel Therapy in Patients Who Failed Intravenous Methylprednisolone (IVMP) for MS Relapses

An Open-Label Prospective Proof-Of-Concept Trial to Evaluate the Response to Acthar Gel Therapy in Patients With Multiple Sclerosis (MS) Relapses Who Have Failed To Make an Adequate Recovery After Treatment With High-Dose Intravenous Methylprednisolone

Although ACTHAR gel is approved for the treatment of acute relapses, it is currently not widely used. Thus, we propose to conduct a small open-label proof-of-concept trial to evaluate the response to ACTHAR gel therapy in patients who have failed to make a satisfactory recovery after treatment with high dose IVMP. Documentation of the clinical course as well as any adverse events related to IVMP use will be made. The investigators propose to study the potential benefit of a 14-day course (the dose historically used since the landmark clinical trial of Rose et al1) of subcutaneous ACTHAR gel in 10 patients who have demonstrated inadequate improvement after a course of IVMP, 1000 mg daily, for 5 treatments (over a maximum of 8 days). These would be patients for whom PLEX would be considered as a treatment possibility. The primary outcome measure will be improvement in the targeted neurological deficit, as measured on the appropriate functional system score (FSS) of the EDSS.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Acthar Gel

Detailed Description

This is an open-label, small, proof-of-concept study examining the safety, tolerability, and extent of recovery of a two-week course of subcutaneous Acthar Gel therapy in patients with MS relapse who have failed to make a satisfactory recovery after treatment with high dose methylprednisolone. Eligible patients will be given 80 units of Acthar for 14 days. Patients will be evaluated at baseline, at 1 week of Acthar treatment, at completion of Acthar treatment, and 1 week after completion of treatment. For those who do not undergo plasmapheresis an additional evaluation will be conducted 2 weeks after completion of treatment. Monitoring will include blood pressure determination and blood sugar determination.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tarah Herrmann; Phone Number: 212-241-4264; Email: tarah.gustafson@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Aaron Miller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18-65
• EDSS of 2.0 - 7.5 (inclusive)
• Sustained a significant MS exacerbation affecting vision, brainstem, motor, or cerebellar function AND were initially treated with a 5 day course of IVMP within 10 days of the onset of symptoms.
• Failed to make adequate improvement and must initiate Acthar Gel therapy within two weeks (+/- 72 hours) after the first day of 5 treatments with 1000 mg IVMP, as judged by their treating neurologist.
• Must be able to comply with the requirements of the protocol as determined by the investigator.
• Ability to understand the purpose and risks of the study and provide signed and date informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.

Exclusion Criteria:

• Patients whose relapse consists of pure sensory or bowel/bladder symptoms
• History of ACTHAR gel use or other forms of ACTH with failure to improve or with occurrence of significant adverse experiences.
• Diagnosis of scleroderma, systemic fungal infections, ocular herpes simplex, congestive heart failure, and/or uncontrolled hypertension, and/or any clinically relevant medical disease that would put the patient at risk by participating in the study
• Persistent significant or severe infection
• Recent history of drug or alcohol abuse
• Concomitant use or prior use in the preceding 6 months of any investigational drug.
• Pregnant or nursing
• Recent surgery (up to the investigator's discretion what constitutes recent)
• History of, or the presence of, a peptic ulcer
• Known sensitivity to proteins of porcine origin
• Received a live or live attenuated vaccine in the last 30 days before baseline

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: Acthar Gel; 80 units of subcutaneous Acthar Gel therapy daily	Drug: Acthar Gel; 80 units of subcutaneous Acthar Gel therapy daily; Other Names: Repository corticotrophin injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Functional System Score appropriate to the Targeted Neurological Deficit	Primary outcome measure will be the percentage of patients improving by at least 1 step on the FSS appropriate to their neurological deficit (targeted neurological deficit [TND]} at 1 week following completion of treatment	at one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Expanded Disability Status Scale	Secondary outcome measures will be improvement in TND at completion of ACTHAR Gel therapy, improvement by at least 1 step on EDSS at completion of treatment and at 1 week following completion of treatment.	baseline and at 1 week

Collaborators and Investigators

• Sponsor: Aaron Miller
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Aaron Miller, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Fred Lublin, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Stephen Krieger, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Michelle Fabian, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Ilana Katz-Sand, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Sylvia Klineova, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Gretchen Mathewson, NP, Icahn School of Medicine at Mount Sinai; Principal Investigator: Aliza Ben-Zacharia, NP, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: July 11, 2013
• First Submitted That Met QC Criteria: July 15, 2013
• First Posted (Estimate): July 16, 2013

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: GCO 13-0600