EryDex for Ataxia Telangiectasia

(NEAT Trial)

Not currently recruiting at 27 trial locations

Overseen By Pamela Raggi, M.Sc

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Quince Therapeutics S.p.A.

Must not be taking: Steroids

Disqualifiers: Immune impairment, Neoplastic disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EryDex, which uses dexamethasone sodium phosphate (a corticosteroid), to determine its effectiveness on the neurological symptoms of Ataxia Telangiectasia (A-T). A-T is a rare genetic disorder that affects movement and coordination. Participants will receive an IV infusion every 28 days, with some receiving the actual treatment and others a placebo (a substance with no active drug). Suitable candidates have a clinical diagnosis of A-T, can walk independently or with some support, and weigh at least 15 kg (about 33 pounds). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have not used oral or injected steroids for at least 6 weeks before starting. However, you can continue using inhaled or nasal steroids for asthma or allergies, and topical steroids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using dexamethasone sodium phosphate in the EryDex system is generally safe for long-term use in children with ataxia telangiectasia. Studies found that patients who used EryDex for at least 24 months tolerated it well. However, like any treatment, side effects can occur. Some studies raised safety concerns, but overall, most patients managed the treatment well. Prospective trial participants should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Ataxia Telangiectasia?

Unlike the standard treatments for Ataxia Telangiectasia, which often focus on symptom management through physical therapy and medications like steroids, EryDex offers a novel approach. It uses dexamethasone sodium phosphate encapsulated in a patient’s own red blood cells through the EryDex System. This delivery method allows for a more controlled and sustained release of the medication, which could potentially reduce side effects and improve effectiveness. Researchers are excited because this innovative approach targets the underlying issues more directly and could lead to better outcomes for patients.

What evidence suggests that EryDex might be an effective treatment for Ataxia Telangiectasia?

Research has shown that EryDex, which uses dexamethasone sodium phosphate (DSP), may help treat Ataxia Telangiectasia (A-T). In earlier studies, EryDex reduced neurological symptoms in children with A-T. This trial will compare the effects of EryDex, which delivers DSP directly into red blood cells, with a placebo. The goal is to manage symptoms more effectively than the placebo. Overall, early findings suggest EryDex might improve the quality of life for those with A-T by slowing the progression of symptoms. ^{1 3 5 6 7}

Who Is on the Research Team?

Dirk Thye, MD

Principal Investigator

Quince Therapeutics S.p.A.

Are You a Good Fit for This Trial?

This trial is for individuals with a body weight of at least 15 kg who have been clinically diagnosed with Ataxia Telangiectasia (A-T). Participants should be able to walk on their own or occasionally use support and must have genetic confirmation of A-T.

Inclusion Criteria

I can walk on my own or sometimes need support.

Body weight ≥15 kg

My condition is genetically confirmed as Ataxia-Telangiectasia.

Exclusion Criteria

Participation in another clinical study

My immune system is weakened.

History of severe impairment of the immunological system

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EryDex or placebo via IV infusion every 28 days to assess neurological effects

6 months

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone sodium phosphate

Trial Overview The study is testing EryDex, which is dexamethasone sodium phosphate inside red blood cells. It's given through an IV once every month. The goal is to see if it helps with neurological symptoms in A-T patients compared to a placebo.

How Is the Trial Designed?

Group I: Dexamethasone sodium phosphate Experimental Treatment 1 Intervention

IV infusion of dexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes using the EryDex System (EDS)

Group II: Placebo Placebo Group 1 Intervention

IV infusion of placebo encapsulated in autologous erythrocytes using the EryDex System (EDS)

Who Is Running the Clinical Trial?

Quince Therapeutics S.p.A.

Lead Sponsor

Trials

10

Recruited

690+

Erydel

Lead Sponsor

Trials

8

Recruited

550+

Biotrial

Industry Sponsor

Trials

15

Recruited

1,100+

Published Research Related to This Trial

In a study of 15 patients with non-infectious posterior segment uveitis, the dexamethasone intravitreal implant (Ozurdex) significantly reduced central retinal thickness (CRT) and improved best-corrected visual acuity (BCVA) after the first treatment, with 91.4% of eyes showing CRT reduction and 80% showing BCVA improvement.

The effectiveness of the DEX implant was maintained with repeat use, showing similar improvements in CRT and VA, indicating it can be a valuable adjunct treatment alongside other therapies for managing macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema in Chronic Non-infectious Uveitis. Tsang, AC., Virgili, G., Abtahi, M., et al.[2018]

In real-life clinical practice, the average number of dexamethasone implant injections for diabetic macular edema (DME) is about 2.4 per year, with an average interval of approximately 4.9 months between treatments, based on data from three studies involving over 700 prescriptions and patient follow-ups.

The consistency in injection frequency across different studies suggests a need for further research to determine the optimal dosing regimen for dexamethasone in treating DME, as current practices may vary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Real-Life Usage of Intravitreal Dexamethasone Implant in the Treatment of Chronic Diabetic Macular Edema in France. Querques, G., Darvizeh, F., Querques, L., et al.[2018]

In a phase 4 study involving 177 patients with diabetic macular edema (DME), the dexamethasone intravitreal implant (DEX) significantly improved visual acuity, with an average increase of +9.1 letters after the first three injections.

The treatment also led to a substantial reduction in central retinal thickness (CRT) by an average of -137.7 μm, demonstrating its effectiveness in both visual and anatomical outcomes without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study. Singer, MA., Dugel, PU., Fine, HF., et al.[2022]

This study is the first to report that the absolute bioavailability of dexamethasone from topical suspensions is less than 2%, indicating limited effectiveness in reaching the aqueous humor after application.

Intracameral administration of dexamethasone showed a clearance rate of 13.6 µL/min and a volume of distribution of 990 µL, providing valuable pharmacokinetic parameters that can help in designing better ocular delivery systems for dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison. Naageshwaran, V., Ranta, VP., Toropainen, E., et al.[2022]

Dexamethasone (Dex) significantly reduces the sensitivity of C6 glioma cells to methotrexate (MTX), allowing more cells to survive even at high concentrations of MTX.

This protective effect of Dex was also observed in human TE671 cells, indicating that the interaction between Dex and MTX is not limited to a specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. Wolff, JE., Jürgens, H.[2013]

Dexamethasone (Dx) can reduce the effectiveness of cisplatin (cDDP) in inducing apoptosis in osteosarcoma cells, decreasing apoptosis by 10-25% when used as a pre or cotreatment.

The protective effect of Dx is linked to the upregulation of the survival factor Akt and a potential direct action on the mitochondrial apoptotic pathway, suggesting that the timing of glucocorticoid administration in cancer treatment should be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. Meyer, S., Eden, T., Kalirai, H.[2020]

The TROPDEX regimen (tropisetron plus dexamethasone) significantly outperformed the METDEX regimen (metoclopramide, dexamethasone, and diphenhydramine) in preventing acute vomiting in 36 Chinese patients undergoing high-dose cisplatin chemotherapy, achieving complete control in 64% of patients compared to 14% with METDEX.

While TROPDEX was more effective for acute vomiting, both regimens showed similar efficacy in controlling delayed vomiting, and TROPDEX was generally well tolerated, with headache being the most common side effect (27%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial. Chua, DT., Sham, JS., Au, GK., et al.[2022]

Dexamethasone implant (Ozurdex™) is generally considered a safe treatment with minimal adverse events, highlighting its favorable safety profile.

The study presents a rare case of a fractured Ozurdex™ implant occurring immediately after injection, providing insights into potential complications and their outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. Aljohani, SM., Al-Shehri, AM., Al-Rubaie, KR.[2021]

In a study of 51 patients receiving paclitaxel (PTX) with aprepitant (APR) and varying doses of dexamethasone (DEX), the incidence of hypersensitivity reactions (HSR) was similar regardless of whether the DEX dose was reduced (51.5% in the higher dose group vs. 53.8% in the lower dose group).

The results indicate that while it is safe to reduce the DEX dose when using APR, this reduction does not decrease the risk of PTX-induced HSR, suggesting that monitoring for adverse effects remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. Yamamoto, T., Natio, M., Hara, S., et al.[2020]

The Ozurdex dexamethasone drug delivery system (DDS) is an effective biodegradable implant for treating macular edema associated with retinal vein occlusion and other conditions, providing sustained release of dexamethasone directly to the eye.

While the dexamethasone DDS shows a favorable safety profile, potential side effects include temporary cataract formation and elevated intraocular pressure, which can typically be managed with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dexamethasone drug delivery system: indications and evidence. London, NJ., Chiang, A., Haller, JA.[2022]

The mixture of methotrexate and dexamethasone sodium phosphate in 0.9% sodium chloride for intrathecal injection showed excellent stability, with no significant changes in drug concentrations or the appearance of new impurities after mixing.

Visual evaluations and pH monitoring confirmed that the admixture remained clear and stable under normal light conditions, indicating that the two drugs do not negatively affect each other's stability when combined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability and compatibility of methotrexate and dexamethasone in 0.9% sodium chloride for intrathecal injection. Xu, F., Zeng, S.[2021]

The study involving 12 patients and 24 eyes demonstrated that consecutive same-day bilateral intravitreal dexamethasone (Ozurdex) injections are safe and well tolerated, with no complications reported.

This approach may enhance treatment efficiency by reducing the number of patient visits while maintaining safety and clinical effectiveness for conditions like diabetic macular edema and retinal vein occlusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY OF CONSECUTIVE SAME-DAY BILATERAL INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX). Kapoor, KG., Colchao, JB.[2021]

The Surodex Drug Delivery System, containing dexamethasone, is a safe and effective method for reducing inflammation after cataract surgery, showing no significant difference in safety compared to conventional dexamethasone eyedrops.

Surodex demonstrated superior efficacy in reducing aqueous flare levels post-surgery, achieving statistically significant reductions at multiple time points, while conventional eyedrops required more steroid augmentation in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of a new dexamethasone delivery system (Surodex) for treatment of post-cataract surgery inflammation. Tan, DT., Chee, SP., Lim, L., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11800360/

Long-term safety of dexamethasone sodium phosphate ... A phase two study of EryDex in children with ataxia telangiectasia suggested its efficacy (30, 31). Subsequently a large double-blind phase ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39152028/

Safety and efficacy of intra-erythrocyte dexamethasone ... The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in ...

3. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00025-0/fulltext

The ATTeST trial in ataxia telangiectasia: some concerns Additionally, intra-erythrocyte delivery of dexamethasone sodium phosphate was shown to be effective in clinical trials for patients with chronic pulmonary ...

4. ir.quincetx.com ir.quincetx.com/news-releases/news-release-details/quince-therapeutics-presents-data-patient-reported-walking

News Release The objective of the data analysis was to describe the pattern of age-related walking capacity loss in patients with A-T and compare the ...

5. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.70103

Population Pharmacokinetic Modeling and Pediatric Exposure ... The EryDex System (EDS) is a drug/device combination, which has been tested in clinical trials for ataxia telangiectasia (AT).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39917433/

Long-term safety of dexamethasone sodium phosphate ... The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia ...

7. ir.quincetx.com ir.quincetx.com/news-releases/news-release-details/quince-therapeutics-announces-frontiers-neurology-publication

News Release The online publication of safety data from patients with Ataxia-Telangiectasia (AT) treated with EryDex for a minimum of 24 months in Frontiers in Neurology.