Ataxia Telangiectasia, Genetic Syndrome
Conditions
Keywords
Ataxia Telangiectasia, AT, EryDex system, Dexamethasone, Dexamethasone sodium phosphate
Brief summary
Primary Objective To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients. Secondary Objective To evaluate the long-term effect of EDS-EP on health-related Quality of Life (QoL; EQ-5D-5L scale). Exploratory Objective: To evaluate the long-term effect of EDS-EP in treating central nervous system (CNS) symptoms, as measured by the Modified International Cooperative Ataxia Rating Scale (mICARS), and Clinical Global Impression of severity and change (CGI-S/C).
Detailed description
This was an international (North America, Europe, Africa, Asia and Australia), multi-center, prospective, open-label treatment study, designed to continue to provide the study medication to all patients who completed 12 months of treatment (including those treated with placebo) in the ATTeST-IEDAT-02-2015 trial, completed the study assessments, do not present safety contraindication to continuation of treatment, and provided informed consent. The study aimed to collect information on the long-term safety and efficacy of the trial treatment. Patients meeting all selection criteria received monthly infusions of EDS-EP (dose range of \ 14-22 mg DSP/infusion). If this dose of EDS-EP was not tolerated, the patient was discontinued from the study. During the study, long-term efficacy assessments were performed every 6 months, while safety parameters were assessed at each monthly visit. The Schedule of Visits and assessments for the first 12 months were replicated for the second year onwards for patients who continued EryDex treatment beyond 12 months. The analysis of the EryDex long-term safety and tolerability was based on the occurrence of Treatment-Emergent Adverse Events (TEAEs), including Serious AEs and discontinuations due to AEs. The long-term effect was measured by the Modified International Cooperative Ataxia Rating Scale, (mICARS), Rescored mICARS, Clinical Global Impression of severity and change (CGI-S/C) and health-related Quality of Life (QoL; EQ-5D-5L scale). The ICARS, EQ-5D-5L and the CGI-C / S were administered by a properly qualified rater identified at each site who performed the ratings on the efficacy measures. The ICARS rater remained blinded to other assessments and did not have access to the safety data. The CGI rater did not have access to the ICARS ratings or safety data but was able to refer to other scales in scoring the CGI. All patients enrolled in this study have participated in Study ATTeST-IEDAT-02-2015, and there was no de novo enrollment of new patients. EryDel S.p.A (now Quince Therapeutics) decided to discontinue the IEDAT-03-2018 study in India due to the COVID-19 pandemic. On 13 Apr 2022, after the last patient completed one year of EryDex treatment, EryDel S.p.A. communicated the end of the open label extension study IEDAT-03-2018 and the stop of the EryDex treatment for patients in the context of this study.
Interventions
COMBINATION_PRODUCTEryDex System
EryDex System was a combination product that was used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EDS) creating the EDS-end product which was infused into the patients. EryDex treatment consisted of a dose range correspondent to the ATTeST High Dose (obtained by loading 125 mg of DSP to the EryDex process and that, in the ATTeST, resulted in a mean of 17.4 ± 5.4 mg (mean ± standard deviation) of DSP infused to patients) administered via ex vivo encapsulation into EDS that were infused into the patient with A-T. The dose of EryDex treatment was selected to allow collection of long-term safety data on the dose of erythrocyte encapsulated DSP that was considered more effective among the two different doses that were employed in the ATTeST study, based on the analysis of the ATTeST blinded, Phase 3 study data.
Sponsors
Quince Therapeutics S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
It's a open label extension study, so no blinding was applicable.
Intervention model description
Open-label, Long-term, Extension Treatment
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient completed the double-blind period in the ATTeST study and completed the final (Visit 15 / Month 12) Efficacy Assessments of ATTeST or discontinued the study during the COVID-19 pandemic. 2. Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe events / serious adverse events. 3. Body weight \> 15 kg. 4. The patient and his / her 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 also was asked to provide their assent to participate in the study. 5. Patient did not present safety contraindication for continuation of treatment, as determined by the Principal Investigator (PI) according to the procedures described below. Moreover, patients who were discontinued from the ATTeST study during the COVID-19 pandemic were eligible to receive the EryDex treatment in the IEDAT-03-2018 study, in the absence of safety contraindications to continuation of the treatment, and after signing the informed consent. There were no de novo enrolled patients.
Exclusion criteria
Patients who met one or more of the following criteria were not considered to be eligible to participate in the study: General 1. Females that were: 1. Pregnant, or were breast-feeding (for EU countries only) 2. Of childbearing potential, pregnant, or were breast-feeding (for US and Rest of World countries). Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, were eligible. 2. A disability that may prevent the patient from completing all study requirements. 3. Current participation in another clinical study with another investigational drug. 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 increases to \< 200 / mm3 (for patients \> 6 years). 5. Current neoplastic disease. 6. Severe impairment of the immunological system. 7. Severe or unstable pulmonary disease. 8. Uncontrolled diabetes. Patients with diabetes that had been stabilized (i.e., no hypoglycemic or hyperglycemic episodes in the past 3 months) were eligible. 9. Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality. 10. Eligibility of patients with abnormal laboratory test values were determined by the Investigator. 11. Confirmed haemoglobinopathies, e.g., haemoglobin C disease, sickle cell anaemia, or thalassemia. 12. Moderate or severe renal and / or hepatic impairment. 13. Patients who experienced moderate / severe steroid side effects, or moderate / severe adverse events associated with the EryDex treatment administered in the ATTeST study. Prior / Concomitant Medication 14. Requires treatment with an oral or parenteral steroid. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids were permitted. 15. Requires any other concomitant medication prohibited by the protocol. 16. Use of any drug that is a strong inducer / inhibitor of Cytochrome P450 3A4 (CYP3A4).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months) | Assessment of TEAEs, treatment-emergent serious adverse events (TESAE), and adverse events of special interest (AESI) were performed throughout the study, from the time of signing of the ICF at Baseline Visit through to the Final Study Visit (Month 12 or early discontinuation). All patients were to be followed up through 30 days after the Final Visit (Month 12 or early discontinuation) or at least 60 days after the final infusion, whichever was longer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | From Baseline (Visit 1- Day 0) to Month 36 | The EQ-5D included single item measures of 5 health dimensions: * mobility, * self-care, * usual activities, * pain / discomfort, and * anxiety / depression. The EQ-5D-5L included five levels of severity (i.e., no problems, slight problems, moderate problems, severe problems, and extreme problems) for each of the five EQ-5D dimensions. These levels were scored from 1 = no problems to 5 = extreme problems: from 5, min/worst, to 25, best/max).The EQ-5D results were converted into a continuous index score: as for this index score, the closer the value is to 1, the better is the health status. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations. |
| Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | From Baseline (Visit 1- Day 0) to Month 36 | 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. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations. |
| 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 From Baseline (Visit 1 - Day 0) to Month 36 | From Baseline (Visit 1- Day 0) to Month 36 | 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. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations. |
| Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | From Baseline (Visit 1- Day 0) to Month 36 | 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 0, max 12) * Speech Disorder- 2 items (min 0, max 8). An higher scores - both for total and subscores - indicate a higher level of disease impairment. The subscores are added to give the total score. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations. |
Countries
Australia, Belgium, Germany, India, Italy, Norway, Poland, Spain, Tunisia, United Kingdom, United States
Participant flow
Recruitment details
Out of a total of 108 patients who completed the full treatment period (including placebo treatment) in the ATTeST - IEDAT-02 study, 104 patients were enrolled in the IEDAT-03-2018 study (OLE-IEDAT) and comprised the Total Set. These patients signed the ICF, completed the ATTeST study assessments, and did not present safety contraindication prior continuation with the EryDex treatment.
Participants by arm
| Arm | Count |
|---|---|
| Overall Population (Total Set) The Total Set (N=104) included all patients who provided informed consent or assent as documented by a date of informed consent or date of assent on the 'Informed Consent' Electronic Case Report form (eCRF) page. | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Due to the COVID-19 pandemic | 12 |
| Overall Study | Physician Decision | 1 |
| Overall Study | study terminated by sponsor | 71 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Overall Population (Total Set) |
|---|---|
| Age, Categorical <=18 years | 104 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 11.4 years STANDARD_DEVIATION 4.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Region of Enrollment Australia | 2 participants |
| Region of Enrollment Belgium | 3 participants |
| Region of Enrollment Germany | 13 participants |
| Region of Enrollment India | 15 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment Norway | 5 participants |
| Region of Enrollment Poland | 10 participants |
| Region of Enrollment Spain | 11 participants |
| Region of Enrollment Tunisia | 7 participants |
| Region of Enrollment United Kingdom | 11 participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 104 |
| other Total, other adverse events | 98 / 104 |
| serious Total, serious adverse events | 12 / 104 |
Outcome results
Primary
Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study
Assessment of TEAEs, treatment-emergent serious adverse events (TESAE), and adverse events of special interest (AESI) were performed throughout the study, from the time of signing of the ICF at Baseline Visit through to the Final Study Visit (Month 12 or early discontinuation). All patients were to be followed up through 30 days after the Final Visit (Month 12 or early discontinuation) or at least 60 days after the final infusion, whichever was longer.
Time frame: From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months)
Population: Safety Population (SAF): the Safety Analysis Set consisted of all patients who provided informed consent or assent and who received any dose of study medication during IEDAT-03-2018 study. The Safety Analysis Set was used for all safety analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Number of TEAEs | 1232 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Number of Serious TEAEs | 19 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Number of TEAE leading to Death | 0 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Number of TEAE leading to Permanent Withdrawal of Treatment | 5 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Adverse Events During COVID-19 Interruption - On Dose | 5 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Adverse Events During COVID-19 Interruption - Off Dose | 3 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Adverse Events During COVID-19 Interruption - Restart | 55 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Worst Intensity - Mild | 1028 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Worst Intensity - Moderate | 187 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Worst Intensity - Severe | 17 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Closest Relationship to Treatment - Probable | 283 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Closest Relationship to Treatment - Possible | 167 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Closest Relationship to Treatment - Unlikely | 178 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | TEAE by Closest Relationship to Treatment - Not related | 604 Number of events |
| Overall Population (SAF) | Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study | Number of AESI | 83 Number of events |
Secondary
Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36
The EQ-5D included single item measures of 5 health dimensions: * mobility, * self-care, * usual activities, * pain / discomfort, and * anxiety / depression. The EQ-5D-5L included five levels of severity (i.e., no problems, slight problems, moderate problems, severe problems, and extreme problems) for each of the five EQ-5D dimensions. These levels were scored from 1 = no problems to 5 = extreme problems: from 5, min/worst, to 25, best/max).The EQ-5D results were converted into a continuous index score: as for this index score, the closer the value is to 1, the better is the health status. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations.
Time frame: From Baseline (Visit 1- Day 0) to Month 36
Population: Full Analysis Set Population (FAS): the FAS comprised all patients who entered IEDAT-03-2018 study, had a Baseline Efficacy Assessment in IEDAT-03-2018 and who received at least one dose of study medication and had at least one post-Baseline Efficacy Assessment of the ICARS in this extension study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 6 | 0.015 score on a scale | Standard Deviation 0.1131 |
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 12 | -0.022 score on a scale | Standard Deviation 0.1145 |
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 18 | 0.007 score on a scale | Standard Deviation 0.1233 |
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 24 | 0.011 score on a scale | Standard Deviation 0.1746 |
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 30 | -0.021 score on a scale | Standard Deviation 0.1117 |
| Overall Population (SAF) | Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36 | to Month 36 | 0.011 score on a scale | Standard Deviation 0.1242 |
Secondary
Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36
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 0, max 12) * Speech Disorder- 2 items (min 0, max 8). An higher scores - both for total and subscores - indicate a higher level of disease impairment. The subscores are added to give the total score. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations.
Time frame: From Baseline (Visit 1- Day 0) to Month 36
Population: The FAS comprised all patients who entered IEDAT-03-2018 study, had a Baseline Efficacy Assessment in IEDAT-03-2018 and who received at least one dose of study medication and had at least one post-Baseline Efficacy Assessment of the ICARS in this extension study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 6 | 0.7 score on a scale | Standard Deviation 4.09 |
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 12 | 1.5 score on a scale | Standard Deviation 3.36 |
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 30 | 4.5 score on a scale | Standard Deviation 5.41 |
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 36 | 34.0 score on a scale | Standard Deviation 5.17 |
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 18 | 2.7 score on a scale | Standard Deviation 4.28 |
| Overall Population (SAF) | Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36 | to Month 24 | 3.9 score on a scale | Standard Deviation 4.96 |
Secondary
Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36
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. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations.
Time frame: From Baseline (Visit 1- Day 0) to Month 36
Population: The FAS comprised all patients who entered IEDAT-03-2018 study, had a Baseline Efficacy Assessment in IEDAT-03-2018 and who received at least one dose of study medication and had at least one post-Baseline Efficacy Assessment of the ICARS in this extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 6 - Improved (Score 1-3) | 9 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 6 - No change or Worsened (Score 4-7) | 68 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 12 - Improved (Score 1-3) | 14 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 12 - No change or Worsened (Score 4-7) | 45 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 18 - Improved (Score 1-3) | 6 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 18 - No change or Worsened (Score 4-7) | 41 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 24 - Improved (Score 1-3) | 5 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 24 - No change or Worsened (Score 4-7) | 26 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 30 - No change or Worsened (Score 4-7) | 17 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 36 - Improved (Score 1-3) | 3 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 36 - No change or Worsened (Score 4-7) | 16 Participants |
| Overall Population (SAF) | Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36 | Month 30 - Improved (Score 1-3) | 2 Participants |
Secondary
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 From Baseline (Visit 1 - Day 0) to Month 36
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. The efficacy data focus mainly up to Month 36 as afterwards the number of patients / assessments dropped below 20% of the initial sample size, which was required for the efficacy evaluations.
Time frame: From Baseline (Visit 1- Day 0) to Month 36
Population: The FAS comprised all patients who entered IEDAT-03-2018 study, had a Baseline Efficacy Assessment in IEDAT-03-2018 and who received at least one dose of study medication and had at least one post-Baseline Efficacy Assessment of the ICARS in this extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Baseline - CGI-S Score - 0 | 2 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Baseline - CGI-S Score - 1 | 18 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Baseline - CGI-S Score - 2 | 31 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Baseline - CGI-S Score - 3 | 23 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Baseline - CGI-S Score - 4 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 6 - CGI-S Score - 0 | 1 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 6 - CGI-S Score - 1 | 20 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 6 - CGI-S Score - 2 | 30 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 6 - CGI-S Score - 3 | 22 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 6 - CGI-S Score - 4 | 3 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 12 - CGI-S Score - 0 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 12 - CGI-S Score - 1 | 12 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 12 - CGI-S Score - 3 | 17 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 12 - CGI-S Score - 4 | 2 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 18 - CGI-S Score - 0 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 18 - CGI-S Score - 1 | 13 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 18 - CGI-S Score - 2 | 21 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 18 - CGI-S Score - 3 | 12 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 24 - CGI-S Score - 0 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 24 - CGI-S Score - 1 | 10 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 24 - CGI-S Score - 2 | 10 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 24 - CGI-S Score - 3 | 9 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 24 - CGI-S Score - 4 | 2 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 30 - CGI-S Score - 0 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 30 - CGI-S Score - 1 | 5 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 30 - CGI-S Score - 2 | 10 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 30 - CGI-S Score - 3 | 4 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 36 - CGI-S Score - 0 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 36 - CGI-S Score - 1 | 3 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 36 - CGI-S Score - 2 | 10 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 36 - CGI-S Score - 3 | 6 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 36 - CGI-S Score - 4 | 0 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 12 - CGI-S Score - 2 | 28 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 18 - CGI-S Score - 4 | 1 Participants |
| Overall Population (SAF) | 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 From Baseline (Visit 1 - Day 0) to Month 36 | Month 30 - CGI-S Score - 4 | 0 Participants |