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

• ClinicalTrials.gov Identifier: NCT01906658
• Recruitment Status: Completed
• First Posted: July 24, 2013
• Results First Posted: January 6, 2017
• Last Update Posted: January 6, 2017
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Repository corticotropin injection	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Explore the Safety and Tolerability of Acthar in Patients With Amyotrophic Lateral Sclerosis
• Study Start Date: July 2013
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

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: H.P. Acthar Gel; Acthar; ACTH Gel; ACTH
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: H.P. Acthar Gel; Acthar; ACTH Gel; ACTH
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: H.P. Acthar Gel; Acthar; ACTH Gel; ACTH
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: H.P. Acthar Gel; Acthar; ACTH Gel; ACTH

Outcome Measures

Primary Outcome Measures :

1. Proportion of Subjects With Adverse Events (AEs) That Required Study Drug Discontinuation or Could Not be Controlled With Concomitant Medication [ Time Frame: Baseline to Week 8 ]

Secondary Outcome Measures :

1. Proportion of Subjects With Adverse Events That Required Study Drug Discontinuation [ Time Frame: Baseline to Week 8 ]
2. Proportion of Subjects With Adverse Events That Could Not be Controlled by Concomitant Medication [ Time Frame: Baseline to Week 8 ]
3. Proportion of Subjects With Treatment Emergent Suicidality [ Time Frame: Baseline to Week 36 ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Alabama

Questcor Investigational Site

Birmingham, Alabama, United States, 35233

United States, Arizona

Questcor Investigational Site

Phoenix, Arizona, United States, 85018

United States, California

Questcor Investigational Site

San Francisco, California, United States, 94115

Questcor Investigational Site

Stanford, California, United States, 94305

United States, Florida

Questcor Investigational Site

Jacksonville, Florida, United States, 32224

Questcor Investigational Site

Miami, Florida, United States, 33136

Questcor Investigational Site

Tampa, Florida, United States, 33612

United States, Georgia

Questcor Investigational Site

Atlanta, Georgia, United States, 30322

United States, Kansas

Questcor Investigational Site

Kansas City, Kansas, United States, 66160

United States, Minnesota

Questcor Investigational Site

Rochester, Minnesota, United States, 55905

United States, Nebraska

Questcor Investigational Site

Lincoln, Nebraska, United States, 68506

United States, Pennsylvania

Questcor Investigational Site

Hershey, Pennsylvania, United States, 17033

Questcor Investigational Site

Pittsburgh, Pennsylvania, United States, 15212

United States, Tennessee

Questcor Investigational Site

Memphis, Tennessee, United States, 38104

United States, Texas

Questcor Investigational Site

Dallas, Texas, United States, 75214

Questcor Investigational Site

Houston, Texas, United States, 77030

Questcor Investigational Site

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Mallinckrodt

More Information

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT01906658
• Other Study ID Numbers: QSC01-ALS-01
• First Posted: July 24, 2013
• Results First Posted: January 6, 2017
• Last Update Posted: January 6, 2017
• Last Verified: November 2016

Keywords provided by Mallinckrodt:

H.P. Acthar Gel; Acthar; amyotrophic lateral sclerosis; ALS

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Adrenocorticotropic Hormone; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs