A Multi-center, Randomized, Double-blind, Placebocontrolled Trial to Evaluate the Effects of IntraErythrocyte Dexamethasone Sodium Phosphate on Neurological Symptoms in Patients with Ataxia Telangiectasia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- EryDel SpA
- 入组人数
- 180
- 试验地点
- 7
- 主要终点
- To evaluate the effect of two dose ranges (approx 5-10 and approx 14-22 mg DSP/infusion) compared to placebo, on CNS symptoms measured by the ‘Modified’ ICARS in patients with AT.
研究概览
简要总结
This is an international (North America, Europe, Africa, Asia and Australia), 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 AT. 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 DSP/infusion,
- Group 2: EDS-EP dose range of ~14-22 mg DSP/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:
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Patients originally randomized to EDS-EP treatment groups (Group 1 or Group 2) will continue on the same treatment;
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Patients originally randomized to the Placebo group (Group 3) will be rerandomized in equal proportions (1:1) to receive either the EDS-EP ~5-10 mg DSP/infusion or ~14-22 mg DSP/infusion, as follows:
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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;
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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;
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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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 6.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patient meets clinical criteria for diagnosis of AT.
- •The neurological signs of AT (in coordination of the head and eyes in lateral gaze deflection, gait ataxia associated with an inappropriately narrow base) must be documented.
- •2.Patient is in autonomous gait or is helped by periodic use of a support.
- •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.
- •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.
排除标准
- •General 1.Females that are of childbearing potential, pregnant, or are breast-feeding.
- •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.
- •3.Current participation in another clinical study.
- •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 lifethreatening 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.
结局指标
主要结局
To evaluate the effect of two dose ranges (approx 5-10 and approx 14-22 mg DSP/infusion) compared to placebo, on CNS symptoms measured by the ‘Modified’ ICARS in patients with AT.
时间窗: 6 Months and 12 Months
次要结局
- To evaluate the effect of EDS-EP, compared to placebo, in this population on the following efficacy measures:(1. CGI-S of neurological symptoms of AT)
- To evaluate the safety and tolerability of EDS-EP compared to placebo in AT patients, based on the occurrence of Treatment-Emergent Adverse Events (TEAEs), including Serious AEs and discontinuations due to AEs, and changes in vital signs, laboratory parameters, ECGs and physical/neurological examination findings.(6 months)