Undersøgelse for at evaluere ACDN-01 i ABCA4-relateret retinopati (STELLAR)
ACDN-01-001: Open-Label, enkelt stigende dosisundersøgelse til evaluering af sikkerheden, tolerabiliteten og den foreløbige effektivitet af subretinal ACDN-01 hos deltagere med ABCA4-relateret retinopati
This study is an open-label, single ascending dose clinical trial in participants who have ABCA4-related retinopathies. This is the first-in-human clinical trial in which ACDN-01 will be evaluated for safety, tolerability, and preliminary efficacy following a single subretinal injection of ACDN-01.
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
This is an open-label, single ascending dose study of ACDN-01 in adult participants with ABCA4-related retinopathy. The study is designed to evaluate the safety, tolerability, and evidence of biological effect of SAD levels (low, medium, and high) of ACDN-01 when delivered subretinally.
Participants will be followed on study for 2 years for the primary safety and preliminary efficacy endpoints, after which they will continue in the study in a 3-year long-term follow-up period, for a total study duration of 5 years.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
California
-
San Francisco, California, Forenede Stater, 94158
- University of San Francisco
-
-
Florida
-
Gainesville, Florida, Forenede Stater, 32607
- Vitreo Retinal Associates
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Miami, Florida, Forenede Stater, 33136
- Bascom Palmer Eye Institute
-
-
Maryland
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Baltimore, Maryland, Forenede Stater, 21218
- Wilmer Eye Institute at John Hopkins
-
-
Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts Eye and Ear
-
-
Michigan
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Ann Arbor, Michigan, Forenede Stater, 48105
- University of Michigan Kellogg Eye Center
-
-
Ohio
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Cincinnati, Ohio, Forenede Stater, 45245
- Cincinnati Eye Institute
-
-
Oregon
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Portland, Oregon, Forenede Stater, 97239
- Casey Eye Institute OHSU
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Children's Hospital of Philadelphia
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Texas
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Dallas, Texas, Forenede Stater, 75382
- Retina Foundation of the Southwest
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Houston, Texas, Forenede Stater, 77401
- Retina Consultants of Texas
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-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Key Inclusion Criteria:
- Presence of mutations in the ABCA4 gene
- ABCA4 retinopathy phenotype (Stargardt disease type 1 or cone-rod dystrophy)
- Area of atrophy located in the macula of the study eye
- BCVA of 20/50 (0.4 logMAR) or worse
Key Exclusion Criteria:
- The presence of pathogenic or likely pathogenic mutations in other genes known to cause cone-rod dystrophy or Stargardt maculopathy
- Retinal disease other than ABCA4-related retinopathy
- Presence of a medical condition (systemic or ophthalmic), psychiatric condition, including substance abuse disorder, or physical examination or laboratory finding that may in the opinion of the principal investigator and sponsor preclude adherence to the scheduled study visits, safe participation in the study, or affect the results of the study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Low dose of ACDN-01
One time low dose of ACDN-01. |
ACDN-01 is an AAV-based vector carrying a DNA construct encoding for an ABCA4 RNA exon editor. One time administration is via subretinal injection. |
|
Eksperimentel: Mid-dose of ACDN-01
One time mid-dose of ACDN-01. |
ACDN-01 is an AAV-based vector carrying a DNA construct encoding for an ABCA4 RNA exon editor. One time administration is via subretinal injection. |
|
Eksperimentel: High dose of ACDN-01
One time high dose of ACDN-01. |
ACDN-01 is an AAV-based vector carrying a DNA construct encoding for an ABCA4 RNA exon editor. One time administration is via subretinal injection. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Safety and tolerability of ACDN-01 as measured by the number and severity of adverse events and serious adverse events.
Tidsramme: 12 months
|
To evaluate the safety and tolerability of a single dose of ACDN-01 when administered to participants with ABCA4-related retinopathy. |
12 months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum tolerated dose for subsequent clinical evaluation will be determined by review of all available safety and tolerability data.
Tidsramme: 12 months
|
To determine maximum tolerated dose (MTD) for subsequent clinical evaluation. |
12 months
|
|
To evaluate for evidence of preliminary efficacy based on fundus autofluorescence (FAF).
Tidsramme: 24 months
|
To evaluate for evidence of preliminary efficacy based on change from baseline in the study eye in the area of macular atrophy in mm2 as measured on FAF over 24 months. |
24 months
|
|
To evaluate for evidence of preliminary efficacy based on optical coherence tomography (OCT).
Tidsramme: 24 months
|
To evaluate for evidence of preliminary efficacy based on change from baseline in the study eye in change in thickness in retinal layers as measured on OCT, over 24 months. |
24 months
|
Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on best corrected visual acuity.
Tidsramme: 24 months
|
Best Corrected Visual Acuity is measured by number of ETDRS letters read in each eye compared to baseline. |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on patient reported outcome measures.
Tidsramme: 24 months
|
Patient-reported outcome measures will be measured by overall and subscale scores on the Michigan Retinal -Degeneration Questionnaire (MRDQ). |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on contrast sensitivity.
Tidsramme: 24 months
|
Contrast sensitivity is measured using qCSF tests and will measure number of letters read and change in AUC (area under curve). |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on contrast sensitivity.
Tidsramme: 24 months
|
Contrast sensitivity is measured using Pelli-Robson tests and will measure number of letters read and change in AUC (area under curve). |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on microperimetry.
Tidsramme: 24 months
|
Retinal sensitivity will be measured by change in the location of detectable points. |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on microperimetry.
Tidsramme: 24 months
|
Retinal sensitivity will be measured by change in the intensity (dB) of detectable points. |
24 months
|
|
To assess for evidence of preliminary efficacy of ACDN-01 based on microperimetry.
Tidsramme: 24 months
|
Retinal sensitivity will be measured by change in the number of detectable points. |
24 months
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Murray Abramson, MD, PhD, Ascidian Therapeutics
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- ACDN-01-001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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