NCT02770807

Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 176 (actual)
• Sponsor: Quince Therapeutics S.p.A. · Industry
• Sex: All
• Age: 6 Years
• Healthy volunteers: Not accepted

Summary

Objectives: The objective of study was to evaluate the safety and the efficacy of EryDex (Dexamethasone sodium phosphate encapsulated in autologous erythrocytes, using the EryDex System - EDS) at two dose levels (low dose and high dose DSP/infusion), compared to placebo, on Neurological Symptoms in Patients With Ataxia Telangiectasia. Initial Double-Blind Treatment Period (0 to 6 Months) Primary Efficacy Objective: • Evaluate the effect of EryDex at two dose levels (low dose and high dose DSP/infusion), compared to placebo, on central nervous system (CNS) symptoms measured by the change in the Modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to Month 6 (Visit 9) in patients with ataxia telangiectasia (A-T). Secondary Efficacy Objectives: * Evaluate the effect of EryDex, compared to placebo, on the Clinical Global Impression of Change (CGI-C) in patients with A-T from baseline to Month 6 (Visit 9). * Evaluate the effect of EryDex, compared to placebo, on measures of Clinical Global Impression of Severity (CGI-S; structured) in patients with A-T from baseline to Month 6 (Visit 9) * Evaluate the effect of EryDex, compared to placebo, on measures of Adaptive behavior measures in patients with A-T by the Vineland Adaptive Behavior Scales (VABS) from baseline to Month 6 (Visit 9). Safety Objectives: • Evaluate the safety and tolerability of two non-overlapping doses of EryDex, compared to placebo, in patients with A-T over the 12-month double-blind study duration. Extension Treatment Period (6-12 Months): Primary Objective: • Evaluate the efficacy of EryDex at two dose levels (low dose and high dose DSP/infusion) compared to placebo, in treating CNS symptoms in A-T patients during longer-term treatment (up to 12 months), as measured by the mICARS. Secondary Objectives: * Evaluate the longer-term (up to 12 months) safety and tolerability of EryDex in A-T patients. * Compare the effects of EryDex on the CGI-C and CGI-S (structured), VABS, and QoL using the EQ-5D-5L scale.

Detailed description

This was an international, multi-center, one-year, randomized, prospective, double-blind, placebo-controlled, phase III study. This study was divided into three periods: Screening (Days -30 to -1), 6-month Initial Treatment Period (Months 1-6; Visits 1-9), and 6-month Extension Treatment Period (Months 7-12; Visits 10-15). A total of 175 patients, of the 180 planned, met all selection criteria at baseline, and were randomized in a 1:1:1 fashion to one of the two EDS-EP dose levels or placebo. These patients were 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 (low dose), 59 pts * Group 2: EDS-EP dose range of \~14-22 mg DSP/infusion (high dose), 57 pts * Group 3: Placebo EDS infusion, 59 pts The initial 6-month treatment period was considered complete when the endpoint assessment (at Visit 9/Month 6 or at early discontinuation) was performed for all patients. All patients who completed the assessments over the initial 6 months of the trial were eligible to continue in an additional 6-month, double-blind, placebo- controlled extension, designed to collect information on the longer-term safety and efficacy of the trial treatments. Following completion of the 6-month Initial Treatment Period, patients that met all entry criteria were re-randomized and treated as follows: * Patients originally randomized to one of the two dose levels of EryDex (low dose or high dose; Groups 1 or 2) continued in the same treatment arm. * Patients originally randomized to the Placebo group (Group 3) were re-allocated as defined at the initial randomization in equal proportions (1:1) and received either the EryDex low dose or high dose as follows: * Following 6 months of treatment, one third of the placebo patients were switched to treatment with EryDex, as described above. * After 9 months of treatment, another third of the placebo patients were switched to treatment with EryDex, as described above. * At 12 months, all remaining placebo patients were eligible to switch to open-label treatment with EryDex, as described above.

Conditions

• Nervous System Disease
• Genetic Syndrome

Interventions

Type	Name	Description
DRUG	EryDex Low dose DSP	EDS-EP dose range of \~5-10 mg DSP/infusion
DRUG	EryDex High dose DSP	EDS-EP dose range of \~14-22 mg DSP/infusion
DRUG	Pooled Placebo	EDS processed autologous erythrocytes using a sodium chloride \[NaCl\] solution.

Timeline

• Start date: 2017-03-02
• Primary completion: 2021-05-13
• Completion: 2021-05-13
• First posted: 2016-05-12
• Last updated: 2024-05-10
• Results posted: 2024-05-09

Locations

22 sites across 12 countries: United States, Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, United Kingdom

Regulatory

• FDA-regulated drug study