A Phase IIa Trial to Test Safety and Efficacy Interferon Gamma Treatment in Elevating Frataxin Levels in FRDA Patients

A Phase IIa Clinical Trial to Test the Safety and Efficacy of Interferon Gamma Treatment in Elevating Frataxin Levels in Friedreich's Ataxia (FRDA) Patients

The primary objective of this study is to investigate whether the treatment with IFN gamma can induce significant accumulation of frataxin in FRDA patients, a possibility suggested by pre-clinical evidence in an animal model of the disease.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: gamma interferon

Detailed Description

This is a Phase 2 clinical trial. A total of 10 FRDA patients will be recruited All subjects will be treated with a dose of 100-150-200-micrograms of IFN gamma 1b (Imukin®) subcutaneously, with an interval of 14 days, for a total of 3 injections.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Italy/Rome
    • Rome, Italy/Rome, Italy, 00161
      • Policlinico Umberto I°

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. FRDA patients should have their diagnosis genetically confirmed.
2. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

4. Male and/or female subjects between the ages of > 18 and < 45 years

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Exclusion Criteria:

1. Pregnant or breastfeeding women.

2. Significant concurrent medical conditions at the time of screening or baseline visit, including, but not limited to, the following:

   • Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, GI, endocrine, pulmonary, immunologic, or local active infection/infectious illness) that, in the investigator's judgment, will substantially increase the risk to the subject if he or she participates in the study.
   • Class III or IV congestive heart failure as defined by the New York Heart Association.
   • Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and any history of significant cerebrovascular disease within 24 weeks before screening.
3. Presence of a transplanted organ.
4. Previous assumption of IFN gamma 1b.

5. Abnormality in any of the below hematology or chemistry profile values at screening:

   • Positive hepatitis B surface antigen (HBsAg), Total hepatitis B core antibody (HBcAb; also called anti HBc), and/or hepatitis C antibody (HCVAb) with confirmation by hepatitis C virus ribonucleic acid (HCV RNA).
   • ALT/AST levels > or = 1.5X ULN.
   • Total bilirubin level > or = 1.5 times the ULN.
   • Hemoglobin level < or = 80 gL (8.0 g/dL).
   • Platelet count < or = 100 x 109/L (100,000 cells/mm³) or > or = 1000 x 109/L (1,000,000 cells/mm³).
   • White blood cell count < or = 3.5 x 109/L (3500 cells/mm³).
   • Absolute neutrophil count (ANC) <2000 cells/mm³.
   • Serum creatinine level > or = 177 μmol/ L (2 mg/dL).
   • Glycosylated hemoglobin (HbA1c >10%).
6. Current or history of serious psychiatric disorder or alcohol or drug abuse.
7. Participation in other studies within 30 days before screening and/or during study participation.

8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or ability to comply with study procedures, investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gamma interferon; IFN gamma 1b (Immukin ®) will be administered by subcutaneous route at day 0, 14 and 28 at a dose of 100, 150 and 200 ug respectively.	Drug: gamma interferon; IFN gamma 1b (Immukin ®) will be administered by subcutaneous route at day 0, 14 and 28 at a dose of 100, 150 and 200 ug respectively.; Other Names: Imukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cellular frataxin	The primary endpoint is to test the increase of cellular frataxin after treatment with IFN gamma. Quantitation of cellular frataxin will be performed after 24 hours and 7 days from each study drug administration	24 hours and 7 days from each study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Blood sample	Secondary endpoint is the safety and tolerability of IFN gamma in FRDA patients. The on treatment adverse events and withdrawals due to adverse effects will be reported. Any subject who receives at least 1 dose of investigational product will be included in the evaluation for safety	day 0-14-28-35

Collaborators and Investigators

• Sponsor: Azienda Policlinico Umberto I
• Investigators: Principal Investigator: Carlo Casali, MD, Policlinico Umberto I°

Publications and helpful links

General Publications

• Tomassini B, Arcuri G, Fortuni S, Sandi C, Ezzatizadeh V, Casali C, Condo I, Malisan F, Al-Mahdawi S, Pook M, Testi R. Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model. Hum Mol Genet. 2012 Jul 1;21(13):2855-61. doi: 10.1093/hmg/dds110. Epub 2012 Mar 23.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): July 30, 2014
• Study Completion (Actual): July 30, 2014

Study Registration Dates

• First Submitted: January 12, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Actual): April 21, 2017
• Last Update Submitted That Met QC Criteria: April 20, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: frataxin, gamma interferon, Friedreich ataxia
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: GIFT/1