ACTH in Progressive Forms of MS

Study Overview
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Brief Summary
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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.

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

Conditions
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Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Progressive Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: ACTH
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTH<br>ACTH administered subcutaneously as a pulsed regimen of 3 consecutive days per month | Drug: ACTH<br>* Acthar gel<br>* Other names: Acthar gel;|
| Placebo Comparator: Placebo<br>Placebo subcutaneous injections administered on 3 consecutive days per month | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |