Nervous System DiseasePhase 3ATTeSTNCT02770807
Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients
A Phase 3 study testing EryDex Low dose DSP and EryDex High dose DSP in people with Nervous System Disease and Genetic Syndrome, run by Quince Therapeutics S.p.A. at 22 sites in 12 countries.
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… Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Nervous System Disease, Genetic Syndrome
- What is being tested?
- EryDex Low dose DSP and EryDex High dose DSP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 22 sitesin 12 countries
- Study dates
- 2 Mar 2017to 13 May 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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).
- Patient was investigated for the proven genetic diagnosis of A-T (prior documentation or by central laboratory test report).
- Patient was at least 6 years of age.
- Body weight was >15 kg.
- 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.
Who cannot join
- General
- Females that were:
- Pregnant or breast-feeding (for European Union [EU] countries only).
- 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.
- A disability that may have prevented the patient from completing all study requirements.
- Current participation in another clinical study.
Show all 25Show fewer
- Medical History and Current Status
- 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).
- 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.
- 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.
- 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.
- 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 EryDex.
- 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.
- Used of any drug that is a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) within 4 weeks before baseline.
Trial locations and contacts
22 sites in 12 countries.
22 sites in 12 countries
India7 sites
National Institute of Mental Health and Neurosciences
Bangalore, Karnataka, 560 029
Vijaya Health Centre, Department of Neurology
Chennai, Tamil Nadu, 600026
Nizam's Institute of Medical Sciences
Hyderabad, Telangana, 500082
Amrita Institute of Medical Sciences and Research Centre
Kochi, Kerala, 682041
PD Hinduja National Hospital and Medical Research
Mahīm, Mumbai, 400016
Jaslok Hospital and Research Centre
Mumbai, Maharashtra, 400026
All India Institute of Medical Sciences
New Delhi, 110029
United States4 sites
The Ataxia-Telangiectasia Clinical Center, The Johns Hopkins Hospital
Baltimore, Maryland, 21287-3923
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
UT Health
Houston, Texas, 77030
UCLA-Ataxia Center and HD Center of Exellence
Los Angeles, California, 900951694
Italy2 sites
U.O. Neurologia e Psichiatria dell'Infanzia e dell' Adolescenza. ASST Spedali Civili, Piazzale Spedali Civili, 1
Brescia, 25123
Dipartimento di Pediatria e Neuropsichiatria Infantile, Università Sapienza di Roma, Azienda Policlinico Universitario Umberto I
Rome, 00185
Germany1 site
Klinik für Kinder- und Jugendmedizin Pädiatrische Allergologie, Pneumologie und Mukoviszidose, Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, 60590
Norway1 site
Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital
Oslo
Poland1 site
Department of Clinical Immunology The Children's Memorial Health Institute
Warsaw, 04-730
United Kingdom1 site
Nottingham University Hospitals NHS Trust - Queen's Medical Centre
Nottingham, Nottinghamshire
About this study
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
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.
Read more
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.
Read the 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
- Being tested
- EryDex Low dose DSP, EryDex High dose DSP, Pooled Placebo
- Keywords
- Ataxia Teleangiectasia, AT, EryDex system, Dexamethasone, Dexamethasone sodium phosphate
- Medical subject headings
- Nervous System Diseases, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EryDex Low dose DSPDrug
Also called EryDex System end product
EDS-EP dose range of ~5-10 mg DSP/infusion
EryDex High dose DSPDrug
Also called EryDex System end product
EDS-EP dose range of ~14-22 mg DSP/infusion
Pooled PlaceboDrug
Also called Placebo EDS infusion
EDS processed autologous erythrocytes using a sodium chloride [NaCl] solution.
| Study group | Role | What they receive |
|---|---|---|
| EryDex Low Dose DSP | Experimental | 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 Receives: Drug: EryDex Low dose DSP |
| EryDex High Dose DSP | Experimental | 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 Receives: Drug: EryDex High dose DSP |
| Placebo | Placebo comparator | 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). Receives: Drug: Pooled Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS)
The International Cooperative Ataxia Rating Scale (ICARS) was an assessment of the degree of impairment in patients with cerebellar ataxia and was administered in its entirety; however, the primary efficacy assessment was based on the modified (m)ICARS, which excluded the Oculomotor domain (items 17 to 19) and items 8 to 12 of the Kinetic Functions domain of the ICARS.
The mICARS was a 54 points maximum score (min 0) questionnaire divided into 3 sections:
- Posture and Gait Disturbance section-7 items (min score 0, max score 34)
- Kinetic Function-2 items (min score 0, max score 12)
- Speech Disorder- 2 items (min score 0, max score 8). The assessment was designed to be completed within 30 minutes, and higher scores - both for total and subscores - indicate a higher level of disease impairment. The subscores are added to give the total score.
Measured: to Month 6 (Visit 9)
Secondary outcomes (5)
Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C)
The CGI-C scale assesses the change in the patient's clinical status from baseline using a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change. Clinicians were required to conduct a full clinical interview and examination of the patient.
The interview and examination assessed various aspects of the patient's appearance (grooming, evidence of falls, etc.), ataxia, cognition (orientation, calculation ability, language, ability to follow commands, memory, etc.), apraxia, dysarthria, extrapyramidal motor symptoms, activities of daily living, and mood. The higher the score the worse the outcome.
Measured: to Month 6 (Visit 9)
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
The CGI-S scale measures global severity of illness at a given point in time, and is usually rated on a 7-point, Likert-type scale ranging from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). No version of the CGI-S exists which has been specifically adapted for use in patients with A-T; therefore, a 5-point version was developed that considered the severity of the following symptoms of A-T: ataxia (walking), dysarthria, dysmetria, extrapyramidal symptoms (chorea, myoclonus, dystonia, and tremor), and eye movements. Ratings of none (0), mild (1), moderate (2), severe (3), and very severe (4) were selected based on the level of symptomatology. The higher the score the worse the outcome.
Measured: to Visit 9 (Month 6)
Change From Baseline of Vineland Adaptive Behavior Scale (VABS-II) Scores - Last Observation Carried Forward (LOCF)
VABS-II was a questionnaire to assess adaptive behavior. It contained 4 domains each with 2-3 subdomains, every subdomain contained various items (questions):
- communication (receptive, expressive, written) B) daily living skills (personal, domestic, community) C) socialization (interpersonal relationships, play and leisure time, coping skills) D) motor skills (gross motor, fine motor). The expanded version of the VABS consisted of 540 items, 261 of which used in this trial.
The possible score for each item was from 0 to 4 based on whether the patient performed the activity "never", "rarely", "sometimes", "often" or "almost always".
At the end of each domain section, a total score (the sum of the score for each item) was calculated. Domain A: min score 0, max score 572. Domain B: 0 - 800. Domain C: 0 - 580. Domain D: 0 - 424. A grand total score (A+B+C+D scores) was provided (range:0-2376) The lower the score the higher the disability at each level (domains and subdomains).
Measured: to Visit 9 (Month 6)
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 6
TEAE = Treatment Emergent Adverse Events were any AEs started on or after the day of the first infusion through the day just prior to the day of the Visit 9 ("Month 6") infusion, or <=60 days after last dose if the subject never continued past this period.
Measured: to Visit 9 (Month 6)
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 12
TEAE = Treatment Emergent Adverse Events were any AEs started on or after the day of the first infusion through the day just prior to the day of the Visit 15 ("Month 12") infusion.
Placebo patients who switched to EryDex treatment at 6 and 9 months were not added to the Extension Treatment Period safety data so that the results reported here under are for those patients who remained on placebo from the start of the study till the end of it.
Measured: to Visit 15 (Month 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2016 (estimated)
- Study start2 Mar 2017
- Primary completion13 May 2021
- Study completion13 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nervous System DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Quince Therapeutics S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Guenter R. Janhofer, MD, PhD, Study director, EryDel S.p.A
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02770807
- Sponsor's protocol ID
- IEDAT-02-2015
- Other IDs
- 2015-005241-31, 2015
- Acronym
- ATTeST
- Status last verified
- May 2024
- First submitted
- 2 May 2016
- Last updated
- 10 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koenig MK, Leuzzi V, Gouider R, Yiu EM, Pietrucha B, Stray-Pedersen A, Perlman SL, Wu S, Burgers T, Borgohain R, Kandadai RM, Meyts I, Bucciol G, Udwadia-Hegde A, Yadav R, Roberts D, Dane A, Roden M, Thye D, Horn B, Lederman HM, Whitehouse WP. Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia. Front Neurol. 2025 Jan 23;15:1526914. doi: 10.3389/fneur.2024.1526914. eCollection 2024.
PubMed 39917433Zielen S, Crawford T, Benatti L, Magnani M, Kieslich M, Ryan M, Meyts I, Gulati S, Borgohain R, Yadav R, Pal P, Hegde A, Kumar S, Venkateswar A, Udani V, Vinayan KP, Nissenkorn A, Fazzi E, Leuzzi V, Stray-Pedersen A, Pietrucha B, Pascual SI, Gouider R, Koenig MK, Wu S, Perlman S, Thye D, Janhofer G, Horn B, Whitehouse W, Lederman H. Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2024 Sep;23(9):871-882. doi: 10.1016/S1474-4422(24)00220-5.
PubMed 39152028
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02770807
- Acronym / sponsor ID
- ATTeST / IEDAT-02-2015
- Conditions
- Nervous System Disease, Genetic Syndrome
- Keywords
- Ataxia Teleangiectasia, AT, EryDex system, Dexamethasone, Dexamethasone sodium phosphate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Quince Therapeutics S.p.A.Industry (pharma, biotech, devices)
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 13 May 2021 (actual)
- Study completion
- 13 May 2021 (actual)
- First posted
- 12 May 2016 (estimated)
- Results
- Posted 9 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EryDex Low Dose DSP | Experimental | Drug: EryDex Low dose DSPEDS-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 |
| EryDex High Dose DSP | Experimental | Drug: EryDex High dose DSPEDS-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 | Placebo comparator | Drug: Pooled PlaceboPatients 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). |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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).
- Patient was investigated for the proven genetic diagnosis of A-T (prior documentation or by central laboratory test report).
- Patient was at least 6 years of age.
- Body weight was >15 kg.
Key exclusion criteria (25 listed)
- General
- Females that were:
- A disability that may have prevented the patient from completing all study requirements.
- Current participation in another clinical study.
- Medical History and Current Status
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EryDex Low dose DSPAlso: EryDex System end productEDS-EP dose range of ~5-10 mg DSP/infusion | Drug | EryDex Low Dose DSP |
| EryDex High dose DSPAlso: EryDex System end productEDS-EP dose range of ~14-22 mg DSP/infusion | Drug | EryDex High Dose DSP |
| Pooled PlaceboAlso: Placebo EDS infusionEDS processed autologous erythrocytes using a sodium chloride [NaCl] solution. | Drug | Placebo |
Primary outcome
Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS)
Time frame: to Month 6 (Visit 9)
The International Cooperative Ataxia Rating Scale (ICARS) was an assessment of the degree of impairment in patients with cerebellar ataxia and was administered in its entirety; however, the primary efficacy assessment was based on the modified (m)ICARS, which excluded the Oculomotor domain (items 17 to 19) and items 8 to 12 of the Kinetic Functions domain of the ICARS. The mICARS was a 54 points maximum score (min 0) questionnaire divided into 3 sections: * Posture and Gait Disturbance section-7 items (min score 0, max score 34) * Kinetic Function-2 items (min score 0, max score 12) * Speech Disorder- 2 items (min score 0, max score 8). The assessment was designed to be completed within 30 minutes, and higher scores - both for total and subscores - indicate a higher level of disease impairment. The subscores are added to give the total score.
5 secondary outcomes
Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C)
Time frame: to Month 6 (Visit 9)
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
Time frame: to Visit 9 (Month 6)
Change From Baseline of Vineland Adaptive Behavior Scale (VABS-II) Scores - Last Observation Carried Forward (LOCF)
Time frame: to Visit 9 (Month 6)
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 6
Time frame: to Visit 9 (Month 6)
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 12
Time frame: to Visit 15 (Month 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39917433Koenig MK, Leuzzi V, Gouider R, Yiu EM, Pietrucha B, Stray-Pedersen A, Perlman SL, Wu S, Burgers T, Borgohain R, Kandadai RM, Meyts I, Bucciol G, Udwadia-Hegde A, Yadav R, Roberts D, Dane A, Roden M, Thye D, Horn B, Lederman HM, Whitehouse WP. Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia. Front Neurol. 2025 Jan 23;15:1526914. doi: 10.3389/fneur.2024.1526914. eCollection 2024.
- Derived from this study: PubMed 39152028Zielen S, Crawford T, Benatti L, Magnani M, Kieslich M, Ryan M, Meyts I, Gulati S, Borgohain R, Yadav R, Pal P, Hegde A, Kumar S, Venkateswar A, Udani V, Vinayan KP, Nissenkorn A, Fazzi E, Leuzzi V, Stray-Pedersen A, Pietrucha B, Pascual SI, Gouider R, Koenig MK, Wu S, Perlman S, Thye D, Janhofer G, Horn B, Whitehouse W, Lederman H. Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2024 Sep;23(9):871-882. doi: 10.1016/S1474-4422(24)00220-5.
- Individual participant dataSharing planned: No
Related trials for Nervous System Disease
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
BrainGate2: Feasibility Study of an Intracortical Neural Interface System for Persons With Aphasia (BG-Aphasia-01)
Expressive Aphasia, Aphasia Following Cerebral Infarction
Not yet recruiting
Feasibility of a Robot-Guided Active Play Intervention for Children With Cerebral Palsy
Cerebral Palsy
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guenter R. Janhofer, MD, PhD study director
EryDel S.p.A
22 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EryDex Low dose DSP and EryDex High dose DSP in people with Nervous System Disease and Genetic Syndrome, run by Quince Therapeutics S.p.A. at 22 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in India, United States, Italy, Australia, Belgium and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS) (time frame: to Month 6 (Visit 9)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02770807, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.