Clinical trial NCT01950234: ACTH in Progressive Forms of MS
Official title: Treatment of Progressive Forms of Multiple Sclerosis With Pulsed ACTH (Acthar Gel)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Secondary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis
Progressive Relapsing Multiple Sclerosis
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2013-09-25
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months
timeFrame: Month 36
Secondary outcomes:
measure: Safety and Tolerability of ACTH: Menstrual Changes [Female]
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: DEXA Scans
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Bruising
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Swelling Ankles
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Hair Loss
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Acne
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Insomnia
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Mood Change
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: GI Upset
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Fatigue
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Unpleasant Taste
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Blurred Vision
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Moon Facies
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Skin Thinning
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Hirsuitism
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Bruising
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Ankle Swelling
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Hair Loss
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Cataracts
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Myopathy
timeFrame: Month 36
measure: Safety and Tolerability of ACTH: Change in Hemoglobin A1c
timeFrame: Month 36
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Clinical Neuroscience Research Unit, University of Minnesota
state: Minnesota
city: Fargo
country: United States
facility: Sanford Clinic Neuroscience
state: North Dakota
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare - St Francis Center for Neurological Disorders
state: Wisconsin
Study officials:
affiliation: University of Minnesota
name: Adam F Carpenter, MD
role: PRINCIPAL_INVESTIGATOR
References: