NCT02770807: ATTeST

Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients

Completed Phase 3 Results posted Last updated 10 May 2024

What this trial tests

Phase 3 trial testing EryDex Low dose DSP in Nervous System Disease in 176 participants. Completed in 13 May 2021.

Timeline

2 March 2017

Primary endpoint
13 May 2021

13 May 2021

Quick facts

Lead sponsor	Quince Therapeutics S.p.A.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	176
Start date	2 March 2017
Primary completion	13 May 2021
Estimated completion	13 May 2021
Sites	22 locations across Tunisia, Italy, Belgium, United Kingdom, Germany, Israel, Norway, Poland

Drugs / interventions tested

• EryDex Low dose DSP — full drug profile →
• EryDex High dose DSP — full drug profile →
• Pooled Placebo — full drug profile →

Conditions studied

• Nervous System Disease — all drugs for Nervous System Disease →
• Genetic Syndrome — all drugs for Genetic Syndrome →

Sponsor

Quince Therapeutics S.p.A. — full company profile →

Who can join

6 and older, any sex, with Nervous System Disease or Genetic Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS) Primary · 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

Group	Value	95% CI
EryDex Low Dose DSP - mITT	0.8	± 3.56
EryDex High Dose DSP - mITT	1.0	± 3.32
Placebo - mITT	2.3	± 5.03

Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) Secondary · to Month 6 (Visit 9)

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 l

Improvement (Scores 1-3)

Group	Value	95% CI
EryDex Low Dose DSP - mITT	19
EryDex High Dose DSP - mITT	27
Placebo - mITT	19

Stable or Worsening (Scores 4-7)

Group	Value	95% CI
EryDex Low Dose DSP - mITT	37
EryDex High Dose DSP - mITT	27
Placebo - mITT	35

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 Secondary · to Visit 9 (Month 6)

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 (

CGI-S Score - 0

Group	Value	95% CI
EryDex Low Dose DSP - mITT	0
EryDex High Dose DSP - mITT	0
Placebo - mITT	0

CGI-S Score - 1

Group	Value	95% CI
EryDex Low Dose DSP - mITT	15
EryDex High Dose DSP - mITT	16
Placebo - mITT	17

CGI-S Score - 2

Group	Value	95% CI
EryDex Low Dose DSP - mITT	29
EryDex High Dose DSP - mITT	26
Placebo - mITT	24

CGI-S Score - 3

Group	Value	95% CI
EryDex Low Dose DSP - mITT	12
EryDex High Dose DSP - mITT	12
Placebo - mITT	13

CGI-S Score - 4

Group	Value	95% CI
EryDex Low Dose DSP - mITT	0
EryDex High Dose DSP - mITT	0
Placebo - mITT	0

Change From Baseline of Vineland Adaptive Behavior Scale (VABS-II) Scores - Last Observation Carried Forward (LOCF) Secondary · to Visit 9 (Month 6)

VABS-II was a questionnaire to assess adaptive behavior. It contained 4 domains each with 2-3 subdomains, every subdomain contained various items (questions): A) 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", "rarel

Group	Value	95% CI
EryDex Low Dose DSP - mITT	42.6	± 125.95
EryDex High Dose DSP - mITT	-26.5	± 214.52
Placebo - mITT	57.5	± 200.37

Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 6 Secondary · to Visit 9 (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.

Patients With Pre- treatment AE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	14
EryDex High Dose DSP - SAF	16
Pooled Placebo - SAF	14

Patients With Any TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	43
EryDex High Dose DSP - SAF	47
Pooled Placebo - SAF	43

Patients With Any Treatment-related TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	15
EryDex High Dose DSP - SAF	21
Pooled Placebo - SAF	15

Patients With Any Serious TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	6
EryDex High Dose DSP - SAF	7
Pooled Placebo - SAF	7

Patients With Any Serious Treatment-related TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	0
EryDex High Dose DSP - SAF	1
Pooled Placebo - SAF	0

Patients With Any TEAE Leading to Discontinuation

Group	Value	95% CI
EryDex Low Dose DSP - SAF	0
EryDex High Dose DSP - SAF	2
Pooled Placebo - SAF	0

Patients With Any TEAE Leading to Death

Group	Value	95% CI
EryDex Low Dose DSP - SAF	0
EryDex High Dose DSP - SAF	0
Pooled Placebo - SAF	0

Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 12 Secondary · to Visit 15 (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.

Patients With Any TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	45
EryDex High Dose DSP - SAF	50
Non-switch Placebo - SAF	15

Patients With Any Treatment-related TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	19
EryDex High Dose DSP - SAF	25
Non-switch Placebo - SAF	5

Patients With Any Serious TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	8
EryDex High Dose DSP - SAF	9
Non-switch Placebo - SAF	4

Patients With Any Serious Treatment-related TEAE

Group	Value	95% CI
EryDex Low Dose DSP - SAF	1
EryDex High Dose DSP - SAF	1
Non-switch Placebo - SAF	1

Patients With Any TEAE Leading to Discontinuation

Group	Value	95% CI
EryDex Low Dose DSP - SAF	1
EryDex High Dose DSP - SAF	2
Non-switch Placebo - SAF	0

Patients With Any TEAE Leading to Death

Group	Value	95% CI
EryDex Low Dose DSP - SAF	0
EryDex High Dose DSP - SAF	0
Non-switch Placebo - SAF	0

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAEs were all the AEs reported up to the end of the Extension Treatment Period (Month 12). All AEs with an onset date on/after the start of the first infusion through 60 days after the last dose are included. A patient with more than one event with the same SOC is counted once. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

EryDex Low Dose DSP - SAF

Serious: 8/59 (14%)

Deaths: 0/59

EryDex High Dose DSP - SAF

Serious: 9/57 (16%)

Deaths: 0/57

Non-switch Placebo - SAF

Serious: 4/19 (21%)

Deaths: 1/19

Placebo Patients Switch to Low Dose - Month 6

Serious: 1/9 (11%)

Deaths: 0/9

Placebo Patients Switch to High Dose - Month 6

Serious: 1/9 (11%)

Deaths: 0/9

Placebo Patients Switch to Low Dose - Month 9

Serious: 1/11 (9%)

Deaths: 0/11

Placebo Patients Switch to High Dose - Month 9

Serious: 4/11 (36%)

Deaths: 0/11

Serious adverse events (14 terms)

Reaction	System	EryDex Low Dose DSP - SAF	EryDex High Dose DSP - SAF	Non-switch Placebo - SAF	Placebo Patients Switch to…	Placebo Patients Switch to…	Placebo Patients Switch to…	Placebo Patients Switch to…
Bacterial test positive	Investigations	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Hepato-Lenticular Degeneration	Congenital, familial and genetic disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Herpes Zoster	Infections and infestations	—	—	—	—	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—
Juvenile idiophatic arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
B-cell limphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Dystonia	Nervous system disorders	—	—	—	—	—	—	—
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Aortic stenosis	Vascular disorders	—	—	—	—	—	—	—

Other adverse events (146 terms — click to expand)

Reaction	System	EryDex Low Dose DSP - SAF	EryDex High Dose DSP - SAF	Non-switch Placebo - SAF	Placebo Patients Switch to…	Placebo Patients Switch to…	Placebo Patients Switch to…	Placebo Patients Switch to…
Pyrexia	General disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Bacterial test positive	Investigations	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Iron deficiency	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—
Osteoporosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Platelet count increased	Investigations	—	—	—	—	—	—	—
White blood cell count increased	Investigations	—	—	—	—	—	—	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Ataxia	Nervous system disorders	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Lethargy	Nervous system disorders	—	—	—	—	—	—	—
Irritability	Psychiatric disorders	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—
Liver disorder	Hepatobiliary disorders	—	—	—	—	—	—	—
Blood iron decreased	Investigations	—	—	—	—	—	—	—
Haemoglobin decreased	Investigations	—	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Iron Deficiency Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Bacterial test positive, Anaemia, Hepato-Lenticular Degeneration, Vomiting, Pyrexia, Herpes Zoster, Lower respiratory tract infection, Pneumonia.

Data from ClinicalTrials.gov NCT02770807 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cell therapies in the clinic.
   Wang LL, Janes ME, Kumbhojkar N, Kapate N, et al · · 2021 · cited 99× · PMID 34027097 · DOI 10.1002/btm2.10214
2. Erythrocytes as Carriers: From Drug Delivery to Biosensors.
   Koleva L, Bovt E, Ataullakhanov F, Sinauridze E. · · 2020 · cited 69× · PMID 32197542 · DOI 10.3390/pharmaceutics12030276
3. Cell-Based Drug Delivery Systems with Innate Homing Capability as a Novel Nanocarrier Platform.
   Choi A, Javius-Jones K, Hong S, Park H. · · 2023 · cited 40× · PMID 36742991 · DOI 10.2147/ijn.s394389
4. Red Blood Cell Membrane Processing for Biomedical Applications.
   Rossi L, Fraternale A, Bianchi M, Magnani M. · · 2019 · cited 37× · PMID 31481901 · DOI 10.3389/fphys.2019.01070
5. Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies.
   Rossi L, Pierigè F, Aliano MP, Magnani M. · · 2020 · cited 34× · PMID 32198632 · DOI 10.1007/s40259-020-00415-0
6. Update on the Treatment of Ataxia: Medication and Emerging Therapies.
   Perlman SL. · · 2020 · cited 21× · PMID 33021724 · DOI 10.1007/s13311-020-00941-3
7. 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.
   Zielen S, Crawford T, Benatti L, Magnani M, et al · · 2024 · cited 17× · PMID 39152028 · DOI 10.1016/s1474-4422(24)00220-5
8. Nucleic Acid Delivery with Red-Blood-Cell-Based Carriers.
   Della Pelle G, Kostevšek N. · · 2021 · cited 17× · PMID 34067699 · DOI 10.3390/ijms22105264