ACTH in Progressive Forms of MS

Phase 2

Terminated

Conditions: Primary Progressive Multiple Sclerosis
Progressive Relapsing Multiple Sclerosis
Secondary Progressive Multiple Sclerosis

Interventions: Drug: Placebo
Drug: ACTH

Registration Number: NCT01950234

Lead Sponsor: University of Minnesota

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 59

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo subcutaneous injections administered on 3 consecutive days per month
ACTH	ACTH	ACTH administered subcutaneously as a pulsed regimen of 3 consecutive days per month

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months	Month 36

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of ACTH: Moon Facies	Month 36	New physician assessed moon facies over study duration
Safety and Tolerability of ACTH: Bruising	Month 36	New physician assessed bruising over study duration
Safety and Tolerability of ACTH: Menstrual Changes [Female]	Month 36	Count of participants self reporting at any time throuhgout the study noticing any changes in menstrual cycle or period.
Safety and Tolerability of ACTH: Swelling Ankles	Month 36	Count of participants self reporting at any time throuhgout the study that have noticed swelling in their ankles
Safety and Tolerability of ACTH: Blurred Vision	Month 36	Count of participants self reporting at any time throuhgout the study noticing any blurred vision
Safety and Tolerability of ACTH: Hair Loss	Month 36	Any new physician assessed hair loss over study duration
Safety and Tolerability of ACTH: Acne	Month 36	Count of participants self reporting at any time throuhgout the study that have noticed in increase in acne
Safety and Tolerability of ACTH: Insomnia	Month 36	Count of participants self reporting at any time throuhgout the study that they have been having trouble sleeping
Safety and Tolerability of ACTH: Mood Change	Month 36	Count of participants self reporting at any time throuhgout the study that they have noticed changes in mood
Safety and Tolerability of ACTH: GI Upset	Month 36	Count of participants self reporting at any time throuhgout the study that they have had upset stomach, indigestion, diarrhea, or bloating
Safety and Tolerability of ACTH: Fatigue	Month 36	Count of participants self reporting at any time throuhgout the study that noticed feeling tired or worn out
Safety and Tolerability of ACTH: Unpleasant Taste	Month 36	Count of participants self reporting at any time throuhgout the study noticing a metallic taste in their mouth
Safety and Tolerability of ACTH: Skin Thinning	Month 36	New physician assessed skin thinning over study duration
Safety and Tolerability of ACTH: Cataracts	Month 36	New physician assessed cataracts over study duration
Safety and Tolerability of ACTH: Myopathy	Month 36	New physician assessed myopathy over study duration
Safety and Tolerability of ACTH: Change in Hemoglobin A1c	Month 36	Change in hemoglobin A1c
Safety and Tolerability of ACTH: DEXA Scans	Month 36	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.
Safety and Tolerability of ACTH: Hirsuitism	Month 36	New physician assessed hirsuitism over study duration
Safety and Tolerability of ACTH: Ankle Swelling	Month 36	New physician assessed ankle swelling over study duration

Trial Locations

Locations (3): Sanford Clinic Neuroscience
🇺🇸
Fargo, North Dakota, United States
Clinical Neuroscience Research Unit, University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Wheaton Franciscan Healthcare - St Francis Center for Neurological Disorders
🇺🇸
Milwaukee, Wisconsin, United States