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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02770807




Registration number
NCT02770807
Ethics application status
Date submitted
2/05/2016
Date registered
12/05/2016
Date last updated
10/05/2024

Titles & IDs
Public title
Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients
Scientific 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
Secondary ID [1] 0 0
2015-005241-31
Secondary ID [2] 0 0
IEDAT-02-2015
Universal Trial Number (UTN)
Trial acronym
ATTeST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nervous System Disease 0 0
Genetic Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EryDex Low dose DSP
Treatment: Drugs - EryDex High dose DSP
Treatment: Drugs - Pooled Placebo

Experimental: EryDex Low Dose DSP - EDS-EP dose range of \~5-10 mg DSP/infusion. This study treatment was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period). Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment).

Other Names:

EryDex System end product Low dose DSP

Experimental: EryDex High Dose DSP - EDS-EP dose range of \~14-22 mg DSP/infusion. This study treatment was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period). Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment).

Other Names:

EryDex System end product High dose DSP

Placebo comparator: Placebo - Patients were treated with autologous erythrocytes prepared with the EDS process using a placebo solution. Placebo was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period).

Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment).


Treatment: Drugs: EryDex Low dose DSP
EDS-EP dose range of \~5-10 mg DSP/infusion

Treatment: Drugs: EryDex High dose DSP
EDS-EP dose range of \~14-22 mg DSP/infusion

Treatment: Drugs: Pooled Placebo
EDS processed autologous erythrocytes using a sodium chloride \[NaCl\] solution.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS)
Timepoint [1] 0 0
to Month 6 (Visit 9)
Secondary outcome [1] 0 0
Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C)
Timepoint [1] 0 0
to Month 6 (Visit 9)
Secondary outcome [2] 0 0
Number of Patients With None to Severe (0 to 4) Scores in Clinical Global Impression of Severity (CGI-S)-Structured of Neurological Symptoms of AT
Timepoint [2] 0 0
to Visit 9 (Month 6)
Secondary outcome [3] 0 0
Change From Baseline of Vineland Adaptive Behavior Scale (VABS-II) Scores - Last Observation Carried Forward (LOCF)
Timepoint [3] 0 0
to Visit 9 (Month 6)
Secondary outcome [4] 0 0
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 6
Timepoint [4] 0 0
to Visit 9 (Month 6)
Secondary outcome [5] 0 0
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 12
Timepoint [5] 0 0
to Visit 15 (Month 12)

Eligibility
Key inclusion criteria
1. Patient met clinical criteria for diagnosis of A-T. The neurological signs of A-T (incoordination of the head and eyes in lateral gaze deflection, gait ataxia associated with an inappropriately narrow base) must have been documented. Such signs of A-T illustrated the body systems in which changes were confirmed, but the listed changes were examples and other changes in those systems may have been observed and documented to confirm the diagnosis of A-T.
2. Patient was in autonomous gait or was helped by periodic use of a support (i.e., score for Item 1 of the full ICARS - Walking Capacities between 0 and 4, included).
3. Patient was investigated for the proven genetic diagnosis of A-T (prior documentation or by central laboratory test report).
4. Patient was at least 6 years of age.
5. Body weight was >15 kg.
6. The patient and parent/caregiver (if below the age of consent), or a legal representative, provided written informed consent to participate. If consent was provided solely by the caregiver in accordance with local regulations, the patient must have provided assent to participate in the study.
Minimum age
6 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

General

1. Females that were:

1. Pregnant or breast-feeding (for European Union [EU] countries only).
2. Of childbearing potential, pregnant, or breast-feeding (for US and Rest of World countries) not using adequate birth control, as determined by their Healthcare Provider.
2. A disability that may have prevented the patient from completing all study requirements.
3. Current participation in another clinical study.

Medical History and Current Status
4. Cluster differential 4 positive (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 increased to <200/mm3 (for patients >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.
10. Any other severe, unstable, or serious disease or condition that in the Investigator's opinion 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 was 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 EryDex.
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. Used of any drug that is a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) within 4 weeks before baseline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/05/2021
Sample size
Target
Accrual to date
Final
176
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Germany
State/province [6] 0 0
Hessen
Country [7] 0 0
India
State/province [7] 0 0
Karnataka
Country [8] 0 0
India
State/province [8] 0 0
Kerala
Country [9] 0 0
India
State/province [9] 0 0
Maharashtra
Country [10] 0 0
India
State/province [10] 0 0
Mumbai
Country [11] 0 0
India
State/province [11] 0 0
Tamil Nadu
Country [12] 0 0
India
State/province [12] 0 0
Telangana
Country [13] 0 0
India
State/province [13] 0 0
New Delhi
Country [14] 0 0
Israel
State/province [14] 0 0
Tel HaShomer
Country [15] 0 0
Italy
State/province [15] 0 0
Brescia
Country [16] 0 0
Italy
State/province [16] 0 0
Rome
Country [17] 0 0
Norway
State/province [17] 0 0
Oslo
Country [18] 0 0
Poland
State/province [18] 0 0
Warsaw
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Tunisia
State/province [20] 0 0
Manouba
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Nottinghamshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Quince Therapeutics S.p.A.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT02770807
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Guenter R. Janhofer, MD, PhD
Address 0 0
EryDel S.p.A
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02770807