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EDS in Ataxia Telangiectasia Patients (ATTeST)

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ClinicalTrials.gov Identifier: NCT02770807
Recruitment Status : Recruiting
First Posted : May 12, 2016
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
Erydel

Tracking Information
First Submitted Date  ICMJE May 2, 2016
First Posted Date  ICMJE May 12, 2016
Last Update Posted Date August 2, 2019
Actual Study Start Date  ICMJE March 2, 2017
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
Modified International Cooperative Ataxia Rating Scale (mICARS) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
Change from baseline analyzed using a Mixed Model Repeated Measures (MMRM) approach
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02770807 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
  • Clinical Global Impression of Change (CGI-C) key secondary outcome measure [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline analyzed using ANCOVA
  • Clinical Global Impression of Severity (CGI-S) of neurological symptoms of AT [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Vineland Adaptive Behavior Scales (VABS) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
  • Clinical Global Impression of Change (CGI-C) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline analyzed using ANCOVA
  • Clinical Global Impression of Severity (CGI-S) of neurological symptoms of AT [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Vineland Adaptive Behavior Scales [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
Current Other Pre-specified Outcome Measures
 (submitted: January 20, 2017)
  • Quality of Life (QoL) EQ-5D-5L scale [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Number of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Vital Signs [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • Laboratory parameters [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • ECGs [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • Number of participants with abnormal physical findings assessed per system [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - questionnaire will be used to assess as normal or abnormal physical findings per system
  • Number of participants with abnormal neurological findings assessed per cranial, motor, sensory, coordination nerves [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - questionnaire will be used to assess as normal or abnormal physical findings per nerve
  • Columbia-Suicide Severity Rating Scale (C- SSR S) Columbia-Suicide Severity Rating Scale (C- SSR S) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline analyzed using ANCOVA
Original Other Pre-specified Outcome Measures
 (submitted: May 10, 2016)
  • Quality of Life (QoL) EQ-5D-5L. [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Number of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline
  • Vital signs [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • Laboratory parameters [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • ECGs [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - results will be summarized descriptively, with abnormal and clinically notable values/findings being identified
  • Number of participants with abnormal physical findings assessed per system [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - questionnaire will be used to assess as normal or abnormal physical findings per system
  • Number of participants with abnormal neurological findings assessed per cranial, motor, sensory, coordination nerves [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline - questionnaire will be used to assess as normal or abnormal physical findings per nerve
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 3 months, 6 months, 9 months, 12 months ]
    Change from baseline will be analyzed using ANCOVA
 
Descriptive Information
Brief Title  ICMJE EDS in Ataxia Telangiectasia Patients
Official Title  ICMJE Multi-center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Effects of Intra-Erythrocyte Dexamethasone Sodium Phosphate on Neurological Symptoms in Patients With Ataxia Telangiectasia
Brief Summary This is an international, multi-center, one-year, randomized, prospective, double-blind, placebo-controlled, phase III study, designed to assess the effect of two non-overlapping dose ranges of EDS EP, administered by IV infusion once per month, on neurological symptoms of patients with Ataxia Telangiectasia.
Detailed Description

All patients who complete the assessments as designed over the initial 6 months of the trial will be eligible to continue in an additional 6-month, double-blind, placebo-controlled extension designed to collect information on the long-term safety and efficacy of the trial treatments.

Upon completion of all screening assessments for eligibility patients meeting all selection criteria at baseline will be randomized in a 1:1:1 fashion to one of the two EDS-EP dose levels or placebo. A minimization procedure will be employed to ensure that the proportions of male and female, and younger (6 to <10 years) and older (≥10 years), patients are comparable across the three treatment groups. Every attempt will be made to ensure the same balance is achieved across different regions.

A minimum of 180 patients will be enrolled, hence, each group will consist of 60 patients randomly assigned to receive one of the two doses of EDS-EP or placebo, as follows:

Group 1: EDS-EP dose range of ~5-10 mg D SP/infusion, Group 2: EDS-EP dose range of ~14-22 mg D SP/infusion, Group 3: Placebo EDS infusion.

The initial 6-month treatment period will be considered complete when the endpoint assessment (at Visit 9/Month 6 or at early discontinuation) has been performed for all patients. Patients who are not experiencing severe side-effects, or have deteriorated significantly while on the treatment and provide informed consent will be eligible to continue treatment for an additional 6 months in a double-blind, placebo-controlled extension treatment period. Patients meeting all entry criteria will be treated as follows:

Patients originally randomized to EDS-EP treatment groups (Group 1 or Group 2) will continue on the same treatment;

Patients originally randomized to the Placebo group (Group 3) will be re-randomized in equal proportions (1:1) to receive either the EDS-EP ~5-10 mg DSP/infusion or ~14-22 mg DSP/infusion, as follows:

Following 6 months of treatment, one third of the originally randomized placebo patients will be re-randomized to treatment with EDS-EP, as described above; After 9 months of treatment, one third of the originally randomized placebo patients will be re-randomized to treatment with EDS-EP, as described above; At 12 months, all remaining placebo patients who continue open-label treatment will receive treatment with EDS-EP, as described above.

The ICARS will be administered by a site rater and scoring verified by a central remote qualified rater, based on a video recording of the assessment at the site. The scores provided by the central remote raters will be used for the primary analysis of the 'Modified' ICARS (primary efficacy endpoint). The site ICARS rater will not be involved in the rating of the CGI- S and CGI-C, VABS, or QoL scale. The CGI rater will not have access to the ICARS ratings, but may refer to other scales in scoring the CGI.

All patients who complete 12 months of treatment in the trial, complete the study assessments, and provide informed consent will be eligible to continue treatment with EDS-EP in an open-label, extension study (IEDAT-03-2016). Retrieved drop-outs (RDO), i.e. patients who discontinued treatment prematurely but completed the final (Visit 15/Month 12) efficacy assessments will also be eligible to enter the open-label extension study. Patients will continue on the dose of EDS-EP they were receiving at the end of Study IEDAT-02, or if on placebo, the patient will be randomly switched (1:1) to one of the two doses of EDS-EP.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double Blind ( Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Nervous System Disease
  • Genetic Syndrome
Intervention  ICMJE
  • Drug: EDS-EP dose range of ~5-10 mg DSP/infusion
    infusion
    Other Name: EryDex System end product
  • Drug: EDS-EP dose range of ~14-22 mg DSP/infusion
    infusion
    Other Name: EryDex System end product
  • Drug: Placebo
    infusion
Study Arms  ICMJE
  • Experimental: EDS-EP dose range of ~5-10 mg DSP/infusion

    Drug: EDS-EP dose range of ~5-10 mg DSP/infusion EDS-EP dose range of ~5-10 mg DSP/infusion: A DSP loading quantity of 50.0 mg will be added to the EDS process, by using 2.0 mL of the 25 mg/mL DSP solution to deliver an EDS dose range of ~5-10 mg. DSP is diluted with 11 mL sterile water for injection in the same syringe, for a total of 13.0 mL.

    Other Names:

    EryDex System end product

    Intervention: Drug: EDS-EP dose range of ~5-10 mg DSP/infusion
  • Experimental: EDS-EP dose range of ~14-22 mg DSP/infusion

    Drug: DSP/infusion EDS-EP dose range of ~14-22 mg DSP/infusion DSP/infusion EDS-EP dose range of ~14-22 mg DSP/infusion: A DSP loading quantity of 125 mg will be added to the EDS process, by using 5.0 mL of the 25 mg/mL DSP solution to deliver an EDS dose range of 14-22 mg. DSP is diluted with 11 mL sterile water for injection in the same syringe, for a total of 16 mL.

    Other Names:

    EryDex System end product

    Intervention: Drug: EDS-EP dose range of ~14-22 mg DSP/infusion
  • Placebo Comparator: Placebo EDS infusion
    Patients will be treated with autologous erythrocytes prepared with the EDS process using a placebo solution (5 mL of 0.372% NaCl solution) instead of experimental drug (DSP). Placebo is diluted with 11 mL sterile water for injection in the same syringe, for a total of 16 mL.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 10, 2016)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • 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.
  • Patient is in autonomous gait or is helped by periodic use of a support.
  • Patient will be investigated for the proven genetic diagnosis of AT (prior documentation or by central laboratory test report).
  • Patient is at least 6 years of age, of either sex
  • Body weight > 15 kg.
  • 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.

Main Exclusion Criteria:

General

  • Females that are

    1. pregnant, or are breast-feeding (for EU countries only);
    2. 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.

  • A disability that may prevent the patient from completing all study requirements.
  • Current participation in another clinical study. Medical History and Current Status
  • CD4+ lymphocytes count <400/mm3 (for patients 6 years of age) or <150/mm3 (for patients >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 <200/mm3 (for patients > 6 years).
  • Loss/removal of 250 mL or more of blood within the past 4 weeks prior to screening.
  • Current neoplastic disease or previous neoplastic disease not in remission for at least 2 years.
  • History of severe impairment of the immunological system.
  • Severe or unstable pulmonary disease.
  • Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible.
  • 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.
  • 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.
  • Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia.
  • Moderate or severe renal and/or hepatic impairment. Prior/Concomitant Medication
  • 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
  • Chronic condition or prior allergic reaction representing a contraindication to the use of dexamethasone or other steroid drugs.
  • 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.
  • Has participated in a previous trial with EDS.
  • Requires any concomitant medication prohibited by the protocol.
  • Has taken a drug or treatment known to cause major organ system toxicity during the past year.
  • Use of any drug that is a strong inducer/inhibitor of CYP3A4 within 4 weeks before baseline.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Irene Maccabruni, M.Sc. +39 0236504470 irene.maccabruni@erydel.com
Contact: Jarno Vannucchi, M.Sc. +39 0236504470 jarno.vannucchi@erydel.com
Listed Location Countries  ICMJE Australia,   Belgium,   Germany,   India,   Israel,   Italy,   Norway,   Poland,   Spain,   Tunisia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02770807
Other Study ID Numbers  ICMJE IEDAT-02-2015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Erydel
Study Sponsor  ICMJE Erydel
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Guenter R. Janhofer, MD, PhD EryDel S.p.A
PRS Account Erydel
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP