A Study to Assess the Efficacy and Safety of H.P. Acthar® Gel in the Treatment of Subjects With Amyotrophic Lateral Sclerosis

This is a multicenter, multiple dose study to examine the effect of Acthar on functional
decline in adult subjects with amyotrophic lateral sclerosis (ALS). Approximately 213
subjects will be enrolled.

Following a screening period of up to 28 days, subjects with ALS and symptom onset (defined
as first muscle weakness or dysarthria) ≤ 2 years prior to the Screening Visit will be
randomized on a 2:1 basis to receive subcutaneous (SC) Acthar 0.2 mL (16 Units [U]) daily
(QD) or SC matching placebo 0.2 mL QD for 36 weeks, followed by a 3 week taper.

Subjects who complete the 36 week double-blind treatment period are eligible to enter an Open
Label Extension phase where all subjects will receive Acthar 0.2 mL (16 U) daily.

Inclusion Criteria:

1. Diagnosis of clinically definite ALS, clinically probable-laboratory supported ALS, or
clinically probable ALS based on revised El Escorial criteria.

2. ALS symptom onset ≤ 2 years prior to the Screening Visit.

3. Subjects who have been on riluzole may enter the study if they have been on a stable
dose of 50 mg BID for ≥ 4 weeks prior to the Screening Visit and, if possible, should
remain on that dose throughout the study.

4. Forced vital capacity (FVC) ≥ 60% at the Screening Visit.

5. Systolic blood pressure ≤ 140 mm Hg and a mean diastolic blood pressure of ≤ 90 mm Hg
at the Screening and Baseline Visits.

Exclusion Criteria:

1. History of use of adrenocorticotropic hormone (ACTH) preparations for treatment of
ALS.

2. Any medical condition known to have an association with motor neuron dysfunction
(other than ALS) which might confound or obscure the diagnosis of ALS.

3. Subject has tracheostomy, diaphragm pacing, or ongoing (used for greater than 7
consecutive days in the 4 weeks prior to the Screening Visit) need for assisted
ventilation of any type.

4. History of chronic active hepatitis including active or chronic hepatitis B, or acute
or chronic hepatitis C.

5. History of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact
with an individual with an active TB infection.

6. Clinically significant infection requiring intravenous administration of antibiotics
and hospitalization in the 4 weeks prior to the Screening Visit.

7. Subject has used edaravone in the 1 week prior to the Screening Visit or in the 2
weeks prior to the Randomization Visit.