Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Multiple Sclerosis, Acthar Gel, ACTH, Fatigue
Brief summary
This is a study of Acthar gel (ACTH) in patients with relapsing multiple sclerosis who are experiencing chronic fatigue.
Detailed description
This is a multi-center, randomized, double-blind, placebo-controlled study to demonstrate the safety, tolerability, and effect of ACTH on fatigue in patients with relapsing multiple sclerosis (RMS). The primary objective of this study is to assess the efficacy of ACTH versus placebo in reducing fatigability in patients with RMS. Secondary objectives include assessment of the tolerability and safety of twice-weekly ACTH treatment vs. placebo and evaluation of ACTH on depression, sleepiness, and quality of life measures and correlations between these measures.
Interventions
DRUGACTH
ACTH injections twice weekly for 28 weeks.
DRUGPlacebo
Placebo injections twice weekly for 28 weeks.
Sponsors
Mallinckrodt
Providence Health & Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have documented diagnosis of Relapsing MS as defined by McDonald Criteria 2011 Revision for at least 6 months * Have been treated with interferon beta 1a or 1b, glatiramer acetate, fingolimod, dimethyl fumarate, or teriflunomide for at least 6 months, with reported adherence rate of at least 75%, at time of screening * Have an Kurtzke Expanded Disability Status Scale (EDSS) score of 0 to 4, inclusive * Have Modified Fatigue Impact Scale (MFIS) ≥ 38 or Functional Systems Scores (FSS) ≥ 36, Beck Depression Inventory-II (BDI-II) greater than or equal to 19, and Expanded Disability Status Scale (EDSS) greater than or equal to 9 * Women of childbearing potential must employ proven methods to prevent pregnancy during the course of the trial * Able to understand the purpose and risks of the study * Must be willing to sign an inform consent * Must be willing to follow the protocol requirements * Subject must agree not to receive any live or live-attenuated vaccine during the trial
Exclusion criteria
* Have any of the contraindications for Acthar Gel as listed in the approved label, including sensitivity to proteins of porcine origin. * Had treatment of systemic or oral corticosteroids of any type in 90 days prior to baseline/randomization * Had a relapse or documented objective neurologic worsening in 90 days prior to baseline/randomization * Has concurrent neurological disease other than multiple sclerosis * History of sleep apnea * History (within 90 days) of nocturnal pain and / or nocturnal spasms that interferes with or disrupts sleep, or uncontrolled nocturnal restless leg syndrome * History of psychosis, bipolar disorder, mania/hypomania * History of coronary heart disease, congestive heart failure, chronic pulmonary disease, emphysema, anemia, bleeding disorder, gastrointestinal bleeding, intestinal ulcer, clinically significant cardiac arrhythmia, Type I or II diabetes, uncontrolled hypertension, seizure disorder, cardiac arrhythmia, immune deficiency disorder, HIV-AIDS, tuberculosis, or dysthyroidal state (patients with a history of hypothyroidism or hyperthyroidism, which has been corrected to physiological levels will not be excluded) * History of substance abuse, other than tobacco within the past 5 years or current alcohol dependence * Current use of cannabis, opiates, benzodiazepines, barbiturates, gabapentin, pregabalin, topiramate, divalproex sodium, carbamazepine, oxcarbazepine, or any gaba-ergic medications other than tizanidine or Baclofen, which are permitted for spasticity treatment * History of any malignant neoplasm except for past basal cell or squamous cell carcinoma of the skin, that has been successfully treated prior to the screening visit * History of psychosis or history of use of neuroleptics including, but not restricted to, haloperidol, chlorpromazine, aripiprazole, olanzapine, risperidone * History of suicide attempt, current suicidal thinking or is preparing for suicide * Current use of Amphetamines or methylphenidate * Current use of modafinil, or armodafinil * Current use of amantidine * The subject must have had a medication-free interval of: a. 7 days for prior use of: i. methylphenidate, amphetamine or dextroamphetamine ii. modafinil or armodafinil iii. diphenhydramine, phenylephrine, loratadine iv. gabapentin, pregabalin, topiramate, valproate/divalproex v. oxcarbazepine vi. codeine, hydrocodone, oxycodone, diphenhydramine, phenylephrine, gabapentin, pregabalin, topiramate, valproate/divalproex, oxcarbazepine, codeine, hydrocodone, oxycodone b. 14 days for prior use of: i. desloratadine ii. Amantidine iii. alprazolam, lorazepam, morphine, hydromorphone, amantidine, alprazolam, lorazepam iv. morphine, hydromorphone c. 28 days for prior use of: i. clonazepam ii. cannabis or other cannabinoids d. 90 days for prior use of carbamazepine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue at 28 Weeks | 28 weeks | Patient-reported levels of fatigue as measured by score on the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) at 28 weeks. The full-length MFIS consists of 21 items. A higher score on the MFIS indicates a greater impact of fatigue on a patient's activities. The FSS is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. Higher scores on each scale indicate a greater severity of fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression at 28 Weeks | 28 weeks | Patient-reported depression as measured by the Beck Depression Inventory-II (BDI-II) at 28 weeks. The BDI-II is a 21-item self-report multiple-choice inventory used as an indicator of the severity of depression. A higher score indicates a greater severity of depression. |
| Sleepiness at 28 Weeks | 28 weeks | Patient-reported daytime sleepiness as measure by the Epworth Sleepiness Scale (ESS) at 28 weeks. The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life, or their 'daytime sleepiness'. |
| Quality of Life at 28 Weeks | 28 weeks | Patient-reported quality of life as measured by the 36-Item Short Form Health Survey (SF-36) at 28 weeks. The SF-36 is a 36-item, patient-reported survey of patient mental and physical health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ACTH The study drug (ACTH 40 units) will be given subcutaneously twice weekly for 2 weeks. If the patient tolerates this dosage regimen, the dose will be increased to 80 units twice weekly. If the 80 unit dosage is not tolerated, the dosage will be reduced to 40 units twice weekly for the remainder of the 24 week participation. The weekly doses will be given 3 days apart, for example, on every Monday and Thursday or every Tuesday and Friday.
ACTH: ACTH injections twice weekly for 28 weeks. | 4 |
| Placebo Placebo will be given subcutaneously twice weekly for 28 weeks.
Placebo: Placebo injections twice weekly for 28 weeks. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Total | Placebo | ACTH |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 3 Participants | 4 Participants |
| Age, Continuous | 53.25 years | 52 years | 54.5 years |
| Beck Depression Inventory-II (BDI-II) | 11.375 units on a scale | 9.75 units on a scale | 13 units on a scale |
| Fatigue Severity Scale | 48.875 units on a scale | 44.5 units on a scale | 53.25 units on a scale |
| Modified Fatigue Impact Scale (MFIS) | 48.125 units on a scale | 48.5 units on a scale | 47.75 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 8 participants | 4 participants | 4 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 3 Participants |
| SF-36 Physical Score | 41.25 units on a scale | 45 units on a scale | 37.75 units on a scale |
| Short Form (36) Health Survey (SF-36) Mental Score | 45.25 units on a scale | 47.5 units on a scale | 43 units on a scale |
| The Epworth Sleepiness Scale (ESS) | 8.875 units on a scale | 10.75 units on a scale | 7 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Fatigue at 28 Weeks
Patient-reported levels of fatigue as measured by score on the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) at 28 weeks. The full-length MFIS consists of 21 items. A higher score on the MFIS indicates a greater impact of fatigue on a patient's activities. The FSS is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. Higher scores on each scale indicate a greater severity of fatigue.
Time frame: 28 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ACTH | Fatigue at 28 Weeks | MFIS | 56.50 score on a scale |
| ACTH | Fatigue at 28 Weeks | FSS | 55.00 score on a scale |
| Placebo | Fatigue at 28 Weeks | MFIS | 29.00 score on a scale |
| Placebo | Fatigue at 28 Weeks | FSS | 40.00 score on a scale |
Secondary
Depression at 28 Weeks
Patient-reported depression as measured by the Beck Depression Inventory-II (BDI-II) at 28 weeks. The BDI-II is a 21-item self-report multiple-choice inventory used as an indicator of the severity of depression. A higher score indicates a greater severity of depression.
Time frame: 28 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ACTH | Depression at 28 Weeks | 16.50 score on a scale |
| Placebo | Depression at 28 Weeks | 40.00 score on a scale |
Secondary
Quality of Life at 28 Weeks
Patient-reported quality of life as measured by the 36-Item Short Form Health Survey (SF-36) at 28 weeks. The SF-36 is a 36-item, patient-reported survey of patient mental and physical health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.
Time frame: 28 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ACTH | Quality of Life at 28 Weeks | SF-36 Mental | 39.50 score on a scale |
| ACTH | Quality of Life at 28 Weeks | SF-36 Physical | 37.50 score on a scale |
| Placebo | Quality of Life at 28 Weeks | SF-36 Mental | 49.00 score on a scale |
| Placebo | Quality of Life at 28 Weeks | SF-36 Physical | 45.00 score on a scale |
Secondary
Sleepiness at 28 Weeks
Patient-reported daytime sleepiness as measure by the Epworth Sleepiness Scale (ESS) at 28 weeks. The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life, or their 'daytime sleepiness'.
Time frame: 28 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ACTH | Sleepiness at 28 Weeks | 11.00 score on a scale |
| Placebo | Sleepiness at 28 Weeks | 7.00 score on a scale |