Trial Outcomes & Findings for Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia Study (NCT NCT02593773)

Last Updated: 2024-12-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

86 participants

Primary outcome timeframe

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

Results posted on

2024-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Interferon γ-1b Subcutaneous (SC) ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Study STARTED	86
Overall Study COMPLETED	51
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon γ-1b Subcutaneous (SC) ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Study Voluntary Withdrawal	3
Overall Study Study Terminated by Sponsor	31
Overall Study Death	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon γ-1b n=86 Participants SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Age, Continuous	16.8 years STANDARD_DEVIATION 4.05 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

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

Population: Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=86 Participants SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 TEAE	78 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 Related TEAE	61 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 SAE	4 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 Related SAE	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 TEAE Leading to Discontinuation	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs ≥ 1 TEAE Leading to Death	1 participants

PRIMARY outcome

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

Population: Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit. Participants with an assessment at each time point are presented.

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.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=86 Participants SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Baseline ADA = negative	85 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Baseline ADA = positive	1 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Baseline NAb = negative	1 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Baseline NAb = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 4 ADA = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 13 ADA = negative	79 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 13 ADA = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 26 ADA = negative	64 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 26 ADA = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 28 (Follow-up) ADA = negative	56 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 28 (Follow-up) ADA = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Last On Study Assessment ADA = negative	85 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Last On Study Assessment ADA = positive	0 participants
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests Week 4 ADA = negative	84 participants

PRIMARY outcome

Timeframe: 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.

Population: Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

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.

Outcome measures

Outcome data not reported

Adverse Events

Interferon γ-1b

Serious events: 4 serious events

Other events: 66 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Interferon γ-1b n=86 participants at risk SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Cardiac disorders Atrial fibrillation	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Cardiac disorders Cardiogenic shock	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Cardiac disorders Eosinophilic myocarditis	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
General disorders Chest pain	2.3% 2/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Infections and infestations Sepsis	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Injury, poisoning and procedural complications Chest injury	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Investigations Heart rate increased	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Vascular disorders Haemodynamic instability	1.2% 1/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.

Other adverse events

Other adverse events
Measure	Interferon γ-1b n=86 participants at risk SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Blood and lymphatic system disorders Neutropenia	20.9% 18/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Gastrointestinal disorders Abdominal pain upper	5.8% 5/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Gastrointestinal disorders Nausea	15.1% 13/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Gastrointestinal disorders Vomiting	15.1% 13/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
General disorders Chills	5.8% 5/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
General disorders Fatigue	8.1% 7/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
General disorders Pain	8.1% 7/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
General disorders Pyrexia	17.4% 15/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Infections and infestations Gastroenteritis viral	5.8% 5/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Infections and infestations Nasopharyngitis	8.1% 7/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Infections and infestations Sinusitis	5.8% 5/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Infections and infestations Upper respiratory tract infection	8.1% 7/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Musculoskeletal and connective tissue disorders Myalgia	5.8% 5/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Nervous system disorders Dizziness	9.3% 8/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Nervous system disorders Headache	29.1% 25/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Respiratory, thoracic and mediastinal disorders Cough	15.1% 13/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.8% 11/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.5% 9/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Skin and subcutaneous tissue disorders Rash	8.1% 7/86 • Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.

Additional Information

Julie Ball, Executive Director, Clinical Development & Operations

Horizon Pharma Ireland, Ltd, Dublin Ireland

Phone: (224) 383-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
Publication restrictions are in place

Restriction type: OTHER