Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Progressive Relapsing Multiple Sclerosis
Conditions
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.
Interventions
DRUGACTH
Acthar gel
DRUGPlacebo
Placebo
Sponsors
Mallinckrodt
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months | Month 36 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: Bruising | Month 36 | Count of participants self reporting at any time throuhgout the study that they bruise more easily |
| 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: Hair Loss | Month 36 | Count of participants self reporting at any time throuhgout the study that have noticed losing more hair |
| 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: 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: Blurred Vision | Month 36 | Count of participants self reporting at any time throuhgout the study noticing any blurred vision |
| Safety and Tolerability of ACTH: Moon Facies | Month 36 | New physician assessed moon facies over study duration |
| Safety and Tolerability of ACTH: Skin Thinning | Month 36 | New physician assessed skin thinning over study duration |
| 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 |
| 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: Unpleasant Taste | Month 36 | Count of participants self reporting at any time throuhgout the study noticing a metallic taste in their mouth |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ACTH ACTH administered subcutaneously as a pulsed regimen of 3 consecutive days per month
ACTH: Acthar gel | 29 |
| Placebo Placebo subcutaneous injections administered on 3 consecutive days per month
Placebo: Placebo | 30 |
| Total | 59 |
Baseline characteristics
| Characteristic | ACTH | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 9.3 | 51.5 years STANDARD_DEVIATION 10.2 | 53.9 years STANDARD_DEVIATION 9.9 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 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 | 29 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 17 Participants | 19 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 29 / 29 | 29 / 30 |
| serious Total, serious adverse events | 8 / 29 | 7 / 30 |
Outcome results
Primary
Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months | 3 Participants |
| Placebo | Proportion of Patients Exhibiting a 20% Worsening in T25FW at 36 Months | 4 Participants |
Secondary
Safety and Tolerability of ACTH: Acne
Count of participants self reporting at any time throuhgout the study that have noticed in increase in acne
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Acne | 2 Participants |
| Placebo | Safety and Tolerability of ACTH: Acne | 4 Participants |
Secondary
Safety and Tolerability of ACTH: Ankle Swelling
New physician assessed ankle swelling over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Ankle Swelling | 7 Participants |
| Placebo | Safety and Tolerability of ACTH: Ankle Swelling | 5 Participants |
Secondary
Safety and Tolerability of ACTH: Blurred Vision
Count of participants self reporting at any time throuhgout the study noticing any blurred vision
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Blurred Vision | 4 Participants |
| Placebo | Safety and Tolerability of ACTH: Blurred Vision | 7 Participants |
Secondary
Safety and Tolerability of ACTH: Bruising
Count of participants self reporting at any time throuhgout the study that they bruise more easily
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Bruising | 7 Participants |
| Placebo | Safety and Tolerability of ACTH: Bruising | 8 Participants |
Secondary
Safety and Tolerability of ACTH: Bruising
New physician assessed bruising over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Bruising | 4 Participants |
| Placebo | Safety and Tolerability of ACTH: Bruising | 4 Participants |
Secondary
Safety and Tolerability of ACTH: Cataracts
New physician assessed cataracts over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Cataracts | 2 Participants |
| Placebo | Safety and Tolerability of ACTH: Cataracts | 1 Participants |
Secondary
Safety and Tolerability of ACTH: Change in Hemoglobin A1c
Change in hemoglobin A1c
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Change in Hemoglobin A1c | 0.14 percent | Standard Deviation 0.36 |
| Placebo | Safety and Tolerability of ACTH: Change in Hemoglobin A1c | 0.05 percent | Standard Deviation 0.32 |
Secondary
Safety and Tolerability of ACTH: DEXA Scans
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.
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACTH | Safety and Tolerability of ACTH: DEXA Scans | -0.41 units on a scale | Standard Deviation 0.49 |
| Placebo | Safety and Tolerability of ACTH: DEXA Scans | 0 units on a scale | Standard Deviation 0.5 |
Secondary
Safety and Tolerability of ACTH: Fatigue
Count of participants self reporting at any time throuhgout the study that noticed feeling tired or worn out
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Fatigue | 16 Participants |
| Placebo | Safety and Tolerability of ACTH: Fatigue | 14 Participants |
Secondary
Safety and Tolerability of ACTH: GI Upset
Count of participants self reporting at any time throuhgout the study that they have had upset stomach, indigestion, diarrhea, or bloating
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: GI Upset | 5 Participants |
| Placebo | Safety and Tolerability of ACTH: GI Upset | 7 Participants |
Secondary
Safety and Tolerability of ACTH: Hair Loss
Count of participants self reporting at any time throuhgout the study that have noticed losing more hair
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Hair Loss | 7 Participants |
| Placebo | Safety and Tolerability of ACTH: Hair Loss | 7 Participants |
Secondary
Safety and Tolerability of ACTH: Hair Loss
Any new physician assessed hair loss over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Hair Loss | 4 Participants |
| Placebo | Safety and Tolerability of ACTH: Hair Loss | 3 Participants |
Secondary
Safety and Tolerability of ACTH: Hirsuitism
New physician assessed hirsuitism over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Hirsuitism | 1 Participants |
| Placebo | Safety and Tolerability of ACTH: Hirsuitism | 1 Participants |
Secondary
Safety and Tolerability of ACTH: Insomnia
Count of participants self reporting at any time throuhgout the study that they have been having trouble sleeping
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Insomnia | 12 Participants |
| Placebo | Safety and Tolerability of ACTH: Insomnia | 11 Participants |
Secondary
Safety and Tolerability of ACTH: Menstrual Changes [Female]
Count of participants self reporting at any time throuhgout the study noticing any changes in menstrual cycle or period.
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Menstrual Changes [Female] | 1 Participants |
| Placebo | Safety and Tolerability of ACTH: Menstrual Changes [Female] | 1 Participants |
Secondary
Safety and Tolerability of ACTH: Mood Change
Count of participants self reporting at any time throuhgout the study that they have noticed changes in mood
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Mood Change | 12 Participants |
| Placebo | Safety and Tolerability of ACTH: Mood Change | 11 Participants |
Secondary
Safety and Tolerability of ACTH: Moon Facies
New physician assessed moon facies over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Moon Facies | 0 Participants |
| Placebo | Safety and Tolerability of ACTH: Moon Facies | 0 Participants |
Secondary
Safety and Tolerability of ACTH: Myopathy
New physician assessed myopathy over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Myopathy | 0 Participants |
| Placebo | Safety and Tolerability of ACTH: Myopathy | 0 Participants |
Secondary
Safety and Tolerability of ACTH: Skin Thinning
New physician assessed skin thinning over study duration
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Skin Thinning | 3 Participants |
| Placebo | Safety and Tolerability of ACTH: Skin Thinning | 3 Participants |
Secondary
Safety and Tolerability of ACTH: Swelling Ankles
Count of participants self reporting at any time throuhgout the study that have noticed swelling in their ankles
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Swelling Ankles | 15 Participants |
| Placebo | Safety and Tolerability of ACTH: Swelling Ankles | 9 Participants |
Secondary
Safety and Tolerability of ACTH: Unpleasant Taste
Count of participants self reporting at any time throuhgout the study noticing a metallic taste in their mouth
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACTH | Safety and Tolerability of ACTH: Unpleasant Taste | 4 Participants |
| Placebo | Safety and Tolerability of ACTH: Unpleasant Taste | 3 Participants |