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

Tracking Information

• First Submitted Date: July 15, 2013
• First Posted Date: July 24, 2013
• Results First Submitted Date: November 8, 2016
• Results First Posted Date: January 6, 2017
• Last Update Posted Date: January 6, 2017
• Study Start Date: July 2013
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 8, 2016): 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 ]
• Original Primary Outcome Measures (submitted: July 19, 2013): Proportion of patients with adverse events (AEs) that require study drug discontinuation or cannot be controlled with concomitant medication [ Time Frame: Week 8 ]

Current Secondary Outcome Measures (submitted: November 8, 2016)

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

Original Secondary Outcome Measures (submitted: July 19, 2013)

• Proportion of patients with clinically significant change in routine clinical laboratory testing from baseline [ Time Frame: Week 4, 8, 12, 36, and 40 ]
  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.
• Proportion of patients with clinically significant change in vital signs from baseline [ Time Frame: Week 4, 8, 12, 36, and 40 ]
  Significant change in vital signs from baseline as measured by blood pressure, heart rate, and body temperature.
• Proportion of patients with other adverse events (AEs) [ Time Frame: Week 4, 8, 12 ,36, and 40 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral 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

Other Names:

• H.P. Acthar Gel
• Acthar
• ACTH Gel
• ACTH

Study Arms

• Experimental: Acthar 80 U (1.0 mL) SC twice weekly
  Acthar (Repository Corticotropin Injection) 80 U (1.0 mL) SC twice weekly
  Intervention: Drug: Repository corticotropin injection
• Experimental: Acthar 24 U (0.3 mL) SC daily
  Acthar (Repository Corticotropin Injection) 24 U (0.3 mL) SC daily
  Intervention: Drug: Repository corticotropin injection
• Experimental: Acthar 56 U (0.7 mL) SC twice weekly
  Acthar (Repository Corticotropin Injection) 56 U (0.7 mL) SC twice weekly
  Intervention: Drug: Repository corticotropin injection
• Experimental: Acthar 16 U (0.2 mL) SC daily
  Acthar (Repository Corticotropin Injection) 16 U (0.2 mL) SC daily
  Intervention: Drug: Repository corticotropin injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2016): 43
• Original Estimated Enrollment (submitted: July 19, 2013): 40
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01906658
• Other Study ID Numbers: QSC01-ALS-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mallinckrodt
• Original Responsible Party: Same as current
• Current Study Sponsor: Mallinckrodt
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Mallinckrodt
• Verification Date: November 2016