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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01906658
• Other study ID #: QSC01-ALS-01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 15, 2013
• Last updated: April 4, 2014
• Start date: July 2013
• Est. completion date: December 2014

Study information

• Verified date: April 2014
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Repository corticotropin injection
Acthar given SC twice weekly (80 U or 56 U) or daily (24 U or 16 U) for 8 weeks

Locations

Country	Name	City	State
United States	Questcor Investigational Site	Atlanta	Georgia
United States	Questcor Investigational Site	Birmingham	Alabama
United States	Questcor Investigational Site	Dallas	Texas
United States	Questcor Investigational Site	Hershey	Pennsylvania
United States	Questcor Investigational Site	Houston	Texas
United States	Questcor Investigational Site	Jacksonville	Florida
United States	Questcor Investigational Site	Kansas City	Kansas
United States	Questcor Investigational Site	Lincoln	Nebraska
United States	Questcor Investigational Site	Memphis	Tennessee
United States	Questcor Investigational Site	Miami	Florida
United States	Questcor Investigational Site	Phoenix	Arizona
United States	Questcor Investigational Site	Pittsburgh	Pennsylvania
United States	Questcor Investigational Site	Rochester	Minnesota
United States	Questcor Investigational Site	San Antonio	Texas
United States	Questcor Investigational Site	San Francisco	California
United States	Questcor Investigational Site	Stanford	California
United States	Questcor Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with adverse events (AEs) that require study drug discontinuation or cannot be controlled with concomitant medication		Week 8	Yes
Secondary	Proportion of patients with clinically significant change in routine clinical laboratory testing from baseline	Significant change in routine clinical laboratory testing from baseline as measured by complete blood count, hemoglobin A1c, chemistry (including serum glucose and lipid panel), serum cortisol, and routine urinalysis.	Week 4, 8, 12, 36, and 40	Yes
Secondary	Proportion of patients with clinically significant change in vital signs from baseline	Significant change in vital signs from baseline as measured by blood pressure, heart rate, and body temperature.	Week 4, 8, 12, 36, and 40	Yes
Secondary	Proportion of patients with other adverse events (AEs)		Week 4, 8, 12 ,36, and 40	Yes