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

NCT02593773 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: HZNP-ACT-302
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 4

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.

Conditions

Friedreich's Ataxia

Keywords

Interferon gamma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs

  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.

  Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit)

• Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests

  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.

  Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit)

• Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (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). A negative change from baseline is an improvement.

  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.

Secondary Outcomes (4)

• Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score

  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.

• Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW)

  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.

• Number of FARS-mNeuro Responders and Non-Responders at Week 26

  Week 26

• Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)

  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.

Study Arms (1)

interferon γ-1b

EXPERIMENTAL

Subcutaneous (SC) doses of ACTIMMUNE® TIW for a total of 26 weeks.

Drug: Interferon γ-1b

Interventions

Interferon γ-1b DRUG

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).

Also known as: ACTIMMUNE®

interferon γ-1b

Eligibility Criteria

• Age: 10 Years - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Friedreich's Ataxia Research Alliance: collaborator

Study Sites (4)

University of California, Los Angeles Neurology Clinic

Los Angeles, California, 90038, United States

Location

University of Florida - Clinical Research Center

Gainesville, Florida, 32603, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

interferon gamma-1b

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

This study was terminated early by the Sponsor because the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia was discontinued after Study HZNP-ACT-301 (NCT02415127) failed to meet its primary efficacy endpoint.

Results Point of Contact

• Title: Julie Ball, Executive Director, Clinical Development & Operations
• Organization: Horizon Pharma Ireland, Ltd, Dublin Ireland

clinicaltrials@horizonpharma.com

(224) 383-3000

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: November 2, 2015
• Study Start: December 25, 2015
• Primary Completion: March 21, 2017
• Study Completion: March 21, 2017
• Last Updated: December 19, 2024
• Results First Posted: May 18, 2018

Record last verified: 2024-11

Locations

US (4)