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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Repository corticotropin injection

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Questcor Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Questcor Investigational Site
  • California
    • San Francisco, California, United States, 94115
      • Questcor Investigational Site
    • Stanford, California, United States, 94305
      • Questcor Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Questcor Investigational Site
    • Miami, Florida, United States, 33136
      • Questcor Investigational Site
    • Tampa, Florida, United States, 33612
      • Questcor Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Questcor Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Questcor Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Questcor Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Questcor Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Questcor Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Questcor Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Questcor Investigational Site
  • Texas
    • Dallas, Texas, United States, 75214
      • Questcor Investigational Site
    • Houston, Texas, United States, 77030
      • Questcor Investigational Site
    • San Antonio, Texas, United States, 78229
      • Questcor Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acthar 80 U (1.0 mL) SC twice weekly; Acthar (Repository Corticotropin Injection) 80 U (1.0 mL) SC twice weekly	Drug: Repository corticotropin injection; Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks; Other Names: ACTH; Acthar; ACTH Gel; H.P. Acthar Gel
Experimental: Acthar 24 U (0.3 mL) SC daily; Acthar (Repository Corticotropin Injection) 24 U (0.3 mL) SC daily	Drug: Repository corticotropin injection; Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks; Other Names: ACTH; Acthar; ACTH Gel; H.P. Acthar Gel
Experimental: Acthar 56 U (0.7 mL) SC twice weekly; Acthar (Repository Corticotropin Injection) 56 U (0.7 mL) SC twice weekly	Drug: Repository corticotropin injection; Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks; Other Names: ACTH; Acthar; ACTH Gel; H.P. Acthar Gel
Experimental: Acthar 16 U (0.2 mL) SC daily; Acthar (Repository Corticotropin Injection) 16 U (0.2 mL) SC daily	Drug: Repository corticotropin injection; Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks; Other Names: ACTH; Acthar; ACTH Gel; H.P. Acthar Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 15, 2013
• First Submitted That Met QC Criteria: July 19, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Estimate): January 6, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: ALS; amyotrophic lateral sclerosis; Acthar; H.P. Acthar Gel
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: QSC01-ALS-01