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: Menstrual Changes [Female]	Count of participants self reporting at any time throuhgout the study noticing any changes in menstrual cycle or period.	Month 36
Safety and Tolerability of ACTH: DEXA Scans	The number is a T-score. There is no maximum or minimum value. Mean change in average of 5 DEXA scan values dual-energy x-ray absorptiometry; measures bone mineral density. Higher numbers are better. A DEXA T-score has a mean of 0 and standard deviation of 1, meaning that a T-score represents how many standard deviations a person's bone density is away from the average bone density of a healthy young adult, with a score of 0 indicating average bone density. Higher scores are better, indicating better bone density. A T-score of -1 to +1 is considered normal bone density, a score between -1 and -2.5 indicates osteopenia (low bone mass), and a score of -2.5 or lower indicates osteoporosis.	Month 36
Safety and Tolerability of ACTH: Bruising	Count of participants self reporting at any time throuhgout the study that they bruise more easily	Month 36
Safety and Tolerability of ACTH: Swelling Ankles	Count of participants self reporting at any time throuhgout the study that have noticed swelling in their ankles	Month 36
Safety and Tolerability of ACTH: Hair Loss	Count of participants self reporting at any time throuhgout the study that have noticed losing more hair	Month 36
Safety and Tolerability of ACTH: Acne	Count of participants self reporting at any time throuhgout the study that have noticed in increase in acne	Month 36
Safety and Tolerability of ACTH: Insomnia	Count of participants self reporting at any time throuhgout the study that they have been having trouble sleeping	Month 36
Safety and Tolerability of ACTH: Mood Change	Count of participants self reporting at any time throuhgout the study that they have noticed changes in mood	Month 36
Safety and Tolerability of ACTH: GI Upset	Count of participants self reporting at any time throuhgout the study that they have had upset stomach, indigestion, diarrhea, or bloating	Month 36
Safety and Tolerability of ACTH: Fatigue	Count of participants self reporting at any time throuhgout the study that noticed feeling tired or worn out	Month 36
Safety and Tolerability of ACTH: Unpleasant Taste	Count of participants self reporting at any time throuhgout the study noticing a metallic taste in their mouth	Month 36
Safety and Tolerability of ACTH: Blurred Vision	Count of participants self reporting at any time throuhgout the study noticing any blurred vision	Month 36
Safety and Tolerability of ACTH: Moon Facies	New physician assessed moon facies over study duration	Month 36
Safety and Tolerability of ACTH: Skin Thinning	New physician assessed skin thinning over study duration	Month 36
Safety and Tolerability of ACTH: Hirsuitism	New physician assessed hirsuitism over study duration	Month 36
Safety and Tolerability of ACTH: Bruising	New physician assessed bruising over study duration	Month 36
Safety and Tolerability of ACTH: Ankle Swelling	New physician assessed ankle swelling over study duration	Month 36
Safety and Tolerability of ACTH: Hair Loss	Any new physician assessed hair loss over study duration	Month 36
Safety and Tolerability of ACTH: Cataracts	New physician assessed cataracts over study duration	Month 36
Safety and Tolerability of ACTH: Myopathy	New physician assessed myopathy over study duration	Month 36
Safety and Tolerability of ACTH: Change in Hemoglobin A1c	Change in hemoglobin A1c	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 (Estimated): September 25, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Chronic Progressive
• 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