A Study to Explore the Safety and Tolerability of Acthar in Patients With Amyotrophic Lateral Sclerosis
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Repository corticotropin injection
Intervention description: Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks
Intervention MeSH terms: Adrenocorticotropic Hormone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: H.P. Acthar Gel; Acthar; amyotrophic lateral sclerosis; ALS

Summary:

      This 8-week randomized, open-label evaluation will examine the acute safety and tolerability
      of 4 different dosing regimens of Acthar to inform dose selection for future studies of
      Acthar in patients with Amyotrophic Lateral Sclerosis (ALS). The study will also investigate
      the mean rate of change in the ALSFRS-R total score as an exploratory endpoint to help design
      future studies.

      This study will enroll up to 40 patients and include an optional 28-week open-label extension
      period plus a 3-week treatment taper and 1-week follow up period. After completion of Week 8,
      patients enrolled in a treatment group that is considered safe and tolerable at that time
      have the option to continue into the open-label extension period. A 3-week treatment taper
      and a follow-up visit are planned for all patients enrolled in the study, beginning either at
      Week 8 or at Week 36 if a patient continues into the optional open-label extension period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to provide informed consent.

          -  Diagnosis of clinically definite ALS, clinically probable-laboratory supported ALS,
             clinically probable ALS, or clinically possible ALS based on the revised El Escorial
             criteria.

          -  Patients with ALS ≤ 3 years since symptom onset. Symptom onset is defined as date of
             first muscle weakness or dysarthria.

          -  Upright slow vital capacity (SVC)≥ 60% of predicted.

          -  If taking riluzole and/or Nuedexta®, stable regimen is required for ≥ 30 days prior to
             screening.

          -  Medically (either independently or with caregiver assistance) able to comply with
             study procedures, including subcutaneous (SC) injections of study medication and
             adherence to concomitant medication restrictions.

        Exclusion Criteria:

          -  Any medical condition known to have an association with motor neuron dysfunction which
             might confound or obscure the diagnosis of ALS.

          -  Tracheostomy, diaphragm pacing, or ongoing need for assisted ventilation of any type
             (e.g., bilevel positive airway pressure) for treatment of ALS-related respiratory
             dysfunction (vital capacity of < 60% predicted, nocturnal desaturation, and/or
             nocturnal hypoventilation). Patients on assisted ventilation for other reasons require
             approval from the Medical Monitor. (Supplemental oxygen is acceptable).

          -  Recorded diagnosis or evidence of major psychiatric disorder.

          -  Clinically evident cognitive and/or behavioral impairment that in the opinion of the
             Investigator would impair the ability of the patient to comply with the study
             procedures.

          -  Therapies and/or Medications:

               1. History of prior sensitivity to Acthar or other porcine protein products.

               2. Chronic systemic corticosteroid use, defined as > 20 mg of prednisone or
                  equivalent systemic corticosteroid taken for more than 4 consecutive weeks within
                  6 months prior to randomization. Topical, inhaled, or intra-articular
                  corticosteroids are allowed.

               3. Planned treatment with live or live attenuated vaccines once enrolled in the
                  study.

          -  Participation in another therapeutic (drug or device) investigational study within 30
             days prior to screening.

          -  Type 1 or type 2 diabetes mellitus, or patients currently taking hypoglycemic
             medication.

          -  Contraindication per Acthar Prescribing Information, Appendix D Section 4:
             scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent
             surgery, history of or the presence of peptic ulcer, congestive heart failure,
             uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical
             hyperfunction.

               1. For the purposes of this study, osteoporosis is defined as a history of a lumbar
                  spine and/or femoral neck T-score ≤ -2.5 on bone densitometry (DXA), OR
                  osteoporosis requiring pharmacologic therapy, OR a history of non-traumatic low
                  impact hip or vertebral fracture, OR patient reported history of osteoporosis.

               2. For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months
                  prior to screening.

               3. For the purposes of this study, uncontrolled hypertension is defined as mean
                  systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg on ≥ 3
                  seated readings taken at least 5 minutes apart during the screening period.

               4. For the purposes of this study, congestive heart failure is defined as New York
                  Heart Association Functional Class III-IV.