Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia Study (STEADFAST)

• ClinicalTrials.gov Identifier: NCT02593773
• Recruitment Status: Completed
• First Posted: November 1, 2015
• Results First Posted: May 18, 2018
• Last Update Posted: May 18, 2018
• Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Collaborator: Friedreich's Ataxia Research Alliance
• Information provided by (Responsible Party): Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Description

Brief Summary:

The purpose of this phase 3 multi-center, open-label extension study is to evaluate the long-term safety of ACTIMMUNE® (interferon-γ 1b) in participants with Friedreich's Ataxia.

Condition or disease	Intervention/treatment	Phase
Friedreich's Ataxia	Drug: Interferon γ-1b	Phase 3

Detailed Description:

Participants who complete 26 weeks of blinded treatment in HZNP-ACT-301 (NCT02415127), will be eligible to enter this 6-month study. All participants will receive ACTIMMUNE® 3 times a week (TIW) for 26 weeks. In order to maintain the study blind in HZNP-ACT-301 (NCT02415127), all participants in this open-label extension study will undergo ACTIMMUNE® titration, regardless if they received ACTIMMUNE® or placebo in HZNP-ACT-301 (NCT02415127). The Week 26 Visit from HZNP-ACT-301 (NCT02415127) will serve as the Baseline Visit (Day 1) for this study. During the treatment period, additional clinic visits are scheduled at Weeks 4, 13, and 26; in between clinic visits, participants (and/or caregivers) will be monitored via emails/phone calls on a weekly basis until participants reach their maximum tolerated dose, and on a monthly basis thereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Safety and Efficacy, Open-Label Extension Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia
• Actual Study Start Date: December 25, 2015
• Actual Primary Completion Date: March 21, 2017
• Actual Study Completion Date: March 21, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: interferon γ-1b; Subcutaneous (SC) doses of ACTIMMUNE® TIW for a total of 26 weeks.

Drug: Interferon γ-1b; The study drug dose is planned to be escalated on a weekly basis over the first 4 weeks of treatment (from 10 µg/m² to 25, 50, and 100 µg/m²). The dose may be reduced, interrupted, or held based on tolerability. By Week 13, all participants are to be on a stable tolerated dose of study drug in order to continue study participation; the dose may not be further increased after Week 13, however, it may be reduced on a case-by-case basis to manage drug-related adverse events (AEs).; Other Name: ACTIMMUNE®

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs [ Time Frame: Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) ]
   An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject's baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. An SAE is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event.
2. Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests [ Time Frame: Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit) ]
   NAb testing only for those participants with a positive ADA test. Baseline is defined as the last non-missing measurement/assessment on the date of Week 26 Visit from study HZNP-ACT-301 (NCT02415127). If this measurement was missing or otherwise unavailable, it was the last non-missing measurement/assessment on or prior to first dose in this study. If the participant discontinued the study, then premature withdrawal assessments were mapped to the nearest scheduled visit based on schedule of the assessment and the study day. If the mapped visit was already available then the visit was mapped to the next schedule visit. Last on study assessment is the last non-missing post-baseline assessment for each participant.
3. Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score [ Time Frame: From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. ]
   The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement.

Secondary Outcome Measures :

1. Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score [ Time Frame: From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. ]
   Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement.
2. Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW) [ Time Frame: From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. ]
   The T25FW is a quantitative measure of lower extremity function. Participants are directed to 1 end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the participant walk back the same distance, and the score for the test is the average of the 2 walks (after reciprocal transformation). Participants may use assistive devices when performing this task, with the same assistive device used at each assessment. A negative change from Baseline indicates improvement.
3. Number of FARS-mNeuro Responders and Non-Responders at Week 26 [ Time Frame: Week 26 ]
   A participant was considered a responder if they had an improvement (decrease) of at least 3 points from Baseline at Week 26 for the FARS-mNeuro score. The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment).
4. Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot) [ Time Frame: From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. ]
   The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement.

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 26 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent and child assent, if applicable.
• Completed 26 weeks of blinded treatment in Study HZNP-ACT-301 (NCT02415127).
• If female, the subject is not pregnant or lactating or intending to become pregnant during the study, or within 30 days after the last dose of study drug. Female subjects of child-bearing potential must have a negative urine pregnancy test result at Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), and agree to use a reliable method of contraception throughout the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

• Subjects will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the study protocol or have a concomitant disease or condition that could interfere with the conduct of the study or potentially put the subject at unacceptable risk.

NOTE: Additional inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

United States, California

University of California, Los Angeles Neurology Clinic

Los Angeles, California, United States, 90038

United States, Florida

University of Florida - Clinical Research Center

Gainesville, Florida, United States, 32603

United States, Iowa

University of Iowa Children's Hospital

Iowa City, Iowa, United States, 52242

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Horizon Pharma Ireland, Ltd., Dublin Ireland

Friedreich's Ataxia Research Alliance

Investigators

• Study Director: Julie Ball, MS; Horizon Pharma Ireland, Ltd., Dublin Ireland

  Study Documents (Full-Text)

Documents provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:

Study Protocol  [PDF] September 28, 2016

Statistical Analysis Plan  [PDF] May 22, 2017

More Information

• Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
• ClinicalTrials.gov Identifier: NCT02593773
• Other Study ID Numbers: HZNP-ACT-302
• First Posted: November 1, 2015
• Results First Posted: May 18, 2018
• Last Update Posted: May 18, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:

Interferon gamma

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases; Interferons; Interferon-gamma; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents