ACTH in Progressive Forms of MS

• ClinicalTrials.gov Identifier: NCT01950234
• Recruitment Status: Active, not recruiting
• First Posted: September 25, 2013
• Last Update Posted: August 3, 2022
• Sponsor: University of Minnesota
• Collaborator: Mallinckrodt
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Progressive Relapsing Multiple Sclerosis	Drug: ACTH; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Progressive Forms of Multiple Sclerosis With Pulsed ACTH (Acthar Gel)
• Study Start Date: October 2013
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients exhibiting a 20% worsening in T25FW at 36 months [ Time Frame: Month 36 ]

Secondary Outcome Measures :

1. Safety and tolerability of ACTH [ Time Frame: Month 36 ]
   Safety and tolerability will be assessed via safety lab tests, skin and edema assessments, DEXA scans, symptom questionnaires and adverse event assessments.

Other Outcome Measures:

1. Slowed progression of sustained cognitive disability [ Time Frame: Month 36 ]
   Brief Repeatable Battery of Neuropsychological Tests (BRB-N)
2. Retinal nerve fiber layer thickness [ Time Frame: Month 36 ]
   Decline in retinal nerve fiber layer thickness as measured by optical coherence tomography (OCT)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Minnesota

Clinical Neuroscience Research Unit, University of Minnesota

Minneapolis, Minnesota, United States, 55414

United States, North Dakota

Sanford Clinic Neuroscience

Fargo, North Dakota, United States, 58103

United States, Wisconsin

Wheaton Franciscan Healthcare - St Francis Center for Neurological Disorders

Milwaukee, Wisconsin, United States, 53215

Sponsors and Collaborators

University of Minnesota

Mallinckrodt

Investigators

• Principal Investigator: Adam F Carpenter, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01950234
• Other Study ID Numbers: 110271
• First Posted: September 25, 2013
• Last Update Posted: August 3, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases