Patient with neurological symptoms of Ataxia Telangiectasia MedDRA version: 21.0 Level: PT Classification code 10003594 Term: Ataxia telangiectasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Dexamethasone sodium phosphate
Pharmaceutical Form: Solution for blood fraction modification
INN or Proposed INN: Dexamethasone sodium phosphate
Current Sponsor code: DSP
Other descrip
Sponsors
EryDel S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient meets clinical criteria for diagnosis of AT. The neurological signs of AT (incoordination of the head and eyes in lateral gaze deflection, gait ataxia associated with an inappropriately narrow base) must be documented. Such signs of AT illustrate the body systems in which changes shall be confirmed but the listed changes are examples and other changes in those systems may be observed and documented to confirm the diagnosis of AT. 2. Patient is in autonomous gait or is helped by periodic use of a support (i.e. local ICARS score for Item 1 – Walking Capacities between 0 and 4, included). 3. Patient will be investigated for the proven genetic diagnosis of AT (prior documentation or by central laboratory test report). 4. Patient is at least 6 years of age, of either sex 5. Body weight > 15 kg. 6. The patient and his/her parent/caregiver (if below the age of consent), or a legal representative, has provided written informed consent to participate. If consent is provided solely by the caregiver in accordance with local regulations, the patient must provide assent to participate in the study. Are the trial subjects under 18? yes Number of subjects for this age range: 180 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: General General 1. Females that are a. pregnant, or are breast-feeding (for EU countries only); b. of childbearing potential, pregnant, or are breast-feeding (for US and Rest of World countries). Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, will be eligible. 2. A disability that may prevent the patient from completing all study requirements. 3. Current participation in another clinical study. Medical History and Current Status 4. CD4+ lymphocytes count 6 years). In presence of oral infections, like oral candidiasis, documented at the screening or recurrent as per medical history documentation, the limit increases to 6 years). 5. Loss/removal of 250 mL or more of blood within the past 4 weeks prior to screening. 6. Current neoplastic disease or previous neoplastic disease not in remission for at least 2 years. 7. History of severe impairment of the immunological system. 8. Severe or unstable pulmonary disease. 9. Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible. 10. Any other severe, unstable, or serious disease or condition that in the Investigator’s opinion would put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality. 11. Any clinically significant abnormality on standard laboratory examinations (hematology, biochemistry, urinalysis) at screening that remains abnormal on repeat testing. Eligibility of patients with abnormal laboratory test values will be determined by the Investigator in consultation with the Medical Monitor. 12. Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia. 13. Moderate or severe renal and/or hepatic impairment. Prior/Concomitant Medication 14. Any previous oral or parenteral steroid use within 4 weeks before Baseline. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids will be permitted. 15. Chronic condition or prior allergic reaction representing a contraindication to the use of dexamethasone or other steroid drugs. 16. Has participated in any other trial with an investigational drug and received a dose within 30 days or 10 half-lives (whichever is greater) from the start of the 30-day Screening Period. 17. Has participated in a previous trial with EDS. 18. Requires any concomitant medication prohibited by the protocol. 19. Has taken a drug or treatment known to cause major organ system toxicity during the past year. 20. Use of any drug that is a strong inducer/inhibitor of CYP3A4 within 4 weeks before baseline.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Initial Treatment Period (6 months) To evaluate the effect of two dose ranges (~5-10 and ~14-22 mg DSP/infusion) of EryDex System end product [EDS-EP; the EDS is a combination product that is used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes, creating the EDS end product, which is infused into the patient], compared to placebo, on central nervous system (CNS) symptoms measured by the ‘Modified’ International Cooperative Ataxia Rating Scale (mICARS) in patients with AT. Extension Treatment Period (6 months) To evaluate the efficacy of two dose ranges (~5-10 and ~14-22 mg DSP/infusion) of EDS-EP compared to placebo in treating CNS symptoms in AT patients during long-term treatment (up to 12 months), as measured by the ‘Modified’ ICARS ;Secondary Objective: Initial Treatment Period (6 months) To evaluate the effect of EDS-EP, compared to placebo, in this population on the Clinical Global Impression of Change from baseline (CGI-C) and on the following efficacy measures: - Clinical Global Impression of Severity (CGI-S) of neurological symptoms of AT; - Adaptive behavior measured by the Vineland Adaptive Behavior Scales (VABS); Extension Treatment Period (6 months) To evaluate the long-term (up to 12 months) safety and tolerability of EDS-EP in AT patients; To compare the effects of the two dose ranges of EDS-EP on the clinician’s global impression (CGI-C and CGI-S), adaptive behavior (VABS), and QoL (EQ-5D-5L scale). ;Primary end point(s): The primary efficacy endpoint will be the change from baseline to the follow-up assessments at Days 90 and 180, in the total score on the ‘Modified’ International Cooperative Ataxia Rating Scale (ICARS). ;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint will be the change from baseline to the follow-up assessments at Days 90 and 180, in the total score on the ‘Modified’ International Cooperative Ataxia Rating Scale (ICARS). The analysis will be done once all | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint The key secondary efficacy end point is the CGI-C rating of change from baseline at the follow-up assessments at Days 90 and 180. Other Secondary Efficacy Endpoints The following secondary efficacy endpoints will be assessed in the study: - The change of CGI-S score from baseline to follow-up based on repeated measures at Days 90 and 180 - The change of VABS score from baseline to follow-up based on repeated measures at Days 90 and 180 ;Timepoint(s) of evaluation of this end point: Days 90 and 180 For more details, please refer to study protocol. | — |
Countries
Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, United Kingdom, United States
Contacts
Public ContactClinical Study Manager
Irene Maccabruni at EryDel S.p.A.
Outcome results
None listed