A Study to Explore the Safety and Tolerability of Acthar in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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.

Official Title
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A Study to Explore the Safety and Tolerability of Acthar in Patients With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Repository corticotropin injection


Participation Criteria
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Eligibility Criteria
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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: History of prior sensitivity to Acthar or other porcine protein products. 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. 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. 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. For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months prior to screening. 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. For the purposes of this study, congestive heart failure is defined as New York Heart Association Functional Class III-IV.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acthar 80 U (1.0 mL) SC twice weekly<br>Acthar (Repository Corticotropin Injection) 80 U (1.0 mL) SC twice weekly | Drug: Repository corticotropin injection<br>* Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks<br>* Other names: ACTH;|
| Experimental: Acthar 24 U (0.3 mL) SC daily<br>Acthar (Repository Corticotropin Injection) 24 U (0.3 mL) SC daily | Drug: Repository corticotropin injection<br>* Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks<br>* Other names: ACTH;|
| Experimental: Acthar 56 U (0.7 mL) SC twice weekly<br>Acthar (Repository Corticotropin Injection) 56 U (0.7 mL) SC twice weekly | Drug: Repository corticotropin injection<br>* Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks<br>* Other names: ACTH;|
| Experimental: Acthar 16 U (0.2 mL) SC daily<br>Acthar (Repository Corticotropin Injection) 16 U (0.2 mL) SC daily | Drug: Repository corticotropin injection<br>* Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks<br>* Other names: ACTH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Adverse Events (AEs) That Required Study Drug Discontinuation or Could Not be Controlled With Concomitant Medication |  | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Adverse Events That Required Study Drug Discontinuation |  | Baseline to Week 8 | 
| Proportion of Subjects With Adverse Events That Could Not be Controlled by Concomitant Medication |  | Baseline to Week 8 | 
| Proportion of Subjects With Treatment Emergent Suicidality |  | Baseline to Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H.P. Acthar Gel, Acthar, amyotrophic lateral sclerosis, ALS