Effects of Acthar on Recovery From Cognitive Relapses in MS

This is a prospective, open-label study of Acthar administered as treatment for an acute
cognitive relapse. Primary and secondary endpoints will be collected prior to Acthar
administration and at 3-month follow-up. Comparison will be made to a stable MS control
group.

The objectives of the study are:

1. To replicate prior findings with steroid therapy for MS patients for cognitive relapses,
using instead Acthar Gel as the treating agent. The investigators will determine if the
decrease on cognitive endpoints at the time of relapse exceeds that of stable MS
controls.

2. To compare the effects above to a previously acquired dataset of relapsing patients
treated with steroids. This is a quasi-experimental design in so far as the steroid
treated group data were previously acquired in a separate study.

The primary hypothesis of the study is that, due to the enhanced melanocortin response in
Acthar the recovery from cognitive changes occurring during cognitively focused relapse will
be significant compared to stable MS patients matched on age, time since testing, and
cognitive performance on the SDMT.

Target enrollment for the Acthar treatment group will be 30 MS patients under care at the
Jacobs Neurological Institute with existing neuropsychological baseline in the past four
years in whom a cognitive relapse or new supratentorial GAD enhancing lesion(s) on MRI have
been identified. Cognitive relapse will be identified based on clinical presentation of acute
worsening of cognitive symptoms in the domains of processing speed, concentration, episodic
memory, working memory, and/or fatigue. Patients whose clinical MRI indicate new active GAD
enhancing lesions will be screened for the presence of self-perceived cognitive decline,
without new physical symptoms. Thirty (30) clinically stable MS patients matched on age, time
since testing, and cognitive performance on the SDMT will be recruited from the pool of
patients with existing cognitive baselines.

Inclusion Criteria:

1. Males/Females between 18 and 65 years of age who are capable of understanding and
complying with the protocol (ie. have completed at least a 9th grade education and are
fluent English).

2. Have a diagnosis of Relapsing Remitting MS (RRMS) or early Secondary Progressive MS
(SPMS) as per revised McDonald's Criteria.

3. Have an Expanded Disability Severity Scale (EDSS) of ≤ 7.0.

4. Have had valid neuropsychological testing (NP) within the past 4 years

5. Experiencing an acute cognitive relapse identified by a clinical care provider as a.)
a cognitive symptom of recent origin developing over 48 hours, or b.) supratentorial
GAD enhancing lesions on MRI with confirmed cognitive decline.

- Confirmation of cognitive decline will be obtained by administering the Symbol
Digit Modalities Test (SDMT) as a screening procedure for the study and comparing
it to scores obtained within 4 years (see inclusion criteria #4). Participants
qualify if a raw point change on the SDMT greater than or equal to -3 points is
detected.

6. Are capable of performing the requirements of neuropsychological (NP) testing,
including near visual acuity 20/70 or better with correction.

7. Have given written informed consent prior to any study-related procedure not part of
normal medical care, with the understanding that consent may be withdrawn by the
subject at any time without prejudice to his/her future medical care.

Exclusion Criteria:

1. Are found to have evidence on MRI of new lesions in the brainstem, spinal cord, or
optic nerve.

2. Have clear new physical signs or symptoms that are referable to the cord, brainstem or
optic nerve.

3. Have cognitive deficits/impairment caused by concomitant medication usage, or are
attributable to another medical condition or significant neurological/psychological
disease.

4. Have evidence of current major depression as determined by a positive Beck Depression
Inventory-Fast Screen (BDI-FS) and clinician interview.

5. Patients with changes to medications known to influence cognition (narcotics,
stimulants, etc.) or disease modifying therapy within one month of study initiation
(or within a time frame deemed high risk by treating physician) will be excluded.

6. Are taking any medication, or have any medical condition contraindicated with Acthar.

7. Presence of current infections as determined by clinician interview.

8. Are currently nursing, intentionally seeking pregnancy, or deemed at-risk for
unplanned pregnancy.