Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients — ATTeST  

Genetic Syndrome Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Ataxia
• Ataxia Telangiectasia
• Genetic Syndrome
• Nervous System Disease
• Nervous System Diseases
• Telangiectasis

• NCT number: NCT02770807
• Study type: Interventional
• Source: Quince Therapeutics S.p.A.
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2017
• Completion date: May 13, 2021