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

NCT01906658 | Completed Phase 2 Results

• 1 other identifier: QSC01-ALS-01
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 17

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (4)

Acthar 80 U (1.0 mL) SC twice weekly

EXPERIMENTAL

Acthar (Repository Corticotropin Injection) 80 U (1.0 mL) SC twice weekly

Drug: Repository corticotropin injection

Acthar 24 U (0.3 mL) SC daily

EXPERIMENTAL

Acthar (Repository Corticotropin Injection) 24 U (0.3 mL) SC daily

Drug: Repository corticotropin injection

Acthar 56 U (0.7 mL) SC twice weekly

EXPERIMENTAL

Acthar (Repository Corticotropin Injection) 56 U (0.7 mL) SC twice weekly

Drug: Repository corticotropin injection

Acthar 16 U (0.2 mL) SC daily

EXPERIMENTAL

Acthar (Repository Corticotropin Injection) 16 U (0.2 mL) SC daily

Drug: Repository corticotropin injection

Interventions

Repository corticotropin injection DRUG

Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks

Also known as: H.P. Acthar Gel, Acthar, ACTH Gel, ACTH

Acthar 16 U (0.2 mL) SC daily; Acthar 24 U (0.3 mL) SC daily; Acthar 56 U (0.7 mL) SC twice weekly; Acthar 80 U (1.0 mL) SC twice weekly

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (17)

Questcor Investigational Site

Birmingham, Alabama, 35233, United States

Location

Questcor Investigational Site

Phoenix, Arizona, 85018, United States

Location

Questcor Investigational Site

San Francisco, California, 94115, United States

Location

Questcor Investigational Site

Stanford, California, 94305, United States

Location

Questcor Investigational Site

Jacksonville, Florida, 32224, United States

Location

Questcor Investigational Site

Miami, Florida, 33136, United States

Location

Questcor Investigational Site

Tampa, Florida, 33612, United States

Location

Questcor Investigational Site

Atlanta, Georgia, 30322, United States

Location

Questcor Investigational Site

Kansas City, Kansas, 66160, United States

Location

Questcor Investigational Site

Rochester, Minnesota, 55905, United States

Location

Questcor Investigational Site

Lincoln, Nebraska, 68506, United States

Location

Questcor Investigational Site

Hershey, Pennsylvania, 17033, United States

Location

Questcor Investigational Site

Pittsburgh, Pennsylvania, 15212, United States

Location

Questcor Investigational Site

Memphis, Tennessee, 38104, United States

Location

Questcor Investigational Site

Dallas, Texas, 75214, United States

Location

Questcor Investigational Site

Houston, Texas, 77030, United States

Location

Questcor Investigational Site

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Lawrence Hill
• Organization: Mallinckrodt Pharmaceuticals

lawrence.hill@mallinckrodt.com

908-238-6370

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 24, 2013
• Study Start: July 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 6, 2017
• Results First Posted: January 6, 2017

Record last verified: 2016-11

Locations

US (17)