ACTH in Progressive Forms of MS

Treatment of Progressive Forms of Multiple Sclerosis With Pulsed ACTH (Acthar Gel)

This is a phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the safety, tolerability, and efficacy of adrenocorticotropic hormone (ACTH, Acthar gel) administered as a pulsed regimen consisting of injections on three consecutive days per month in patients with progressive forms of Multiple Sclerosis (MS). Patients will be randomly assigned to either an ACTH arm or a placebo arm. The main hypotheses are that 1) pulsed ACTH will be safe and well-tolerated, and 2) pulsed ACTH will slow progression of clinical and paraclinical measures of MS progression compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis; Progressive Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: ACTH

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Clinical Neuroscience Research Unit, University of Minnesota
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Sanford Clinic Neuroscience
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wheaton Franciscan Healthcare - St Francis Center for Neurological Disorders

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female patients with a confirmed diagnosis of MS by McDonald criteria
• Age >/= 18 years
• SPMS, PPMS, or PRMS phenotype, according to Lublin and Reingold criteria
• EDSS 2.0 - 6.0, inclusive
• Able to understand the consent process

Exclusion Criteria:

• Known intolerance of ACTH or corticosteroids
• Diabetes mellitus, defined as pre-existing diagnosis, fasting blood glucose > 125 mg/dl, or glycosylated hemoglobin >/= 6.5%
• Osteoporosis, defined as pre-existing diagnosis or T-score on dual-energy x-ray absorptiometry (DEXA) scan of </= -2.5.
• Current serious medical condition which may interfere with subject's ability to complete the study, or for which pulsed ACTH therapy is contraindicated or might complicate current therapy (e.g., cancer, severe psychiatric illness, chronic infections, autoimmune disorders)
• Treatment with cytotoxic agents (including but not necessarily limited to mitoxantrone, cyclophosphamide, alemtuzumab, or rituximab) within 3 years prior to randomization
• Treatment with non-cytotoxic immunosuppressive agents (including but not necessarily limited to corticosteroids, ACTH, azathioprine, mycophenolate mofetil, methotrexate or natalizumab) within 3 months prior to randomization
• Treatment with FDA-approved first-line MS disease-modifying therapies (B-interferon, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate) will be permitted, as long as treatment has been ongoing and stable for at least 3 months prior to randomization
• Treatment with dalfampridine or compounded 4-aminopyridine (4-AP) will be permitted as long as treatment has been ongoing and stable for at least 3 months prior to randomization
• Stimulant medications for fatigue (such as methylphenidate, modafinil, armodafinil, amantadine or dextroamphetamine) will be permitted, but subjects will be asked to not take these medications on study visit days until all study procedures/assessments are completed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACTH; ACTH administered subcutaneously as a pulsed regimen of 3 consecutive days per month	Drug: ACTH; Acthar gel; Other Names: Acthar gel
Placebo Comparator: Placebo; Placebo subcutaneous injections administered on 3 consecutive days per month	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients exhibiting a 20% worsening in T25FW at 36 months	Month 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of ACTH	Safety and tolerability will be assessed via safety lab tests, skin and edema assessments, DEXA scans, symptom questionnaires and adverse event assessments.	Month 36

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slowed progression of sustained cognitive disability	Brief Repeatable Battery of Neuropsychological Tests (BRB-N)	Month 36
Retinal nerve fiber layer thickness	Decline in retinal nerve fiber layer thickness as measured by optical coherence tomography (OCT)	Month 36

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Adam F Carpenter, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2014
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: August 30, 2013
• First Submitted That Met QC Criteria: September 20, 2013
• First Posted (Estimate): September 25, 2013

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

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; Multiple Sclerosis, Chronic Progressive; Sclerosis
• Other Study ID Numbers: 110271

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No