Clinical trial NCT04567550: RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) With and Without Center Involved-Diabetic Macular Edema (CI-DME)
Official title: A Phase 2, Randomized, Controlled, Dose-escalation Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via a Single Suprachoroidal Space (SCS) Injections in Participants With Diabetic Retinopathy (DR) With and Without Center Involved-Diabetic Macular Edema (CI-DME)(ALTITUDE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Retinopathy (DR)
Center-Involved Diabetic Macular Edema (CI-DME)
Keywords: DR
CI-DME
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: REGENXBIO Inc.
First posted: 2020-09-28
Enrollment: 130
Sex: ALL
Minimum age (years): 25
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: ABBV-RGX-314 is being developed as a novel, potential one-time gene therapy treatment for the treatment of Diabetic Retinopathy (DR) with and without Center-Involved Diabetic Macular Edema (CI-DME). DR is a chronic and progressive complication of diabetes mellitus. It is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that leads to further deterioration of functional vision. Despite the availability of current treatments, diabetic retinopathy remains the leading cause of vision loss in working-age adults, those between the ages of 20 and 74. Existing treatment with anti-VEGF agents, although shown to be effective, are limited by short therapeutic half-lives, which then require frequent intravitreal injections over the patient's lifetime, resulting in increased risk of associated adverse events and significant treatment burden. Due to the burden of treatment, patients often do not closely adhere to treatment regimens and experience sub-optimal outcomes and a decline in vision.

Detailed description: This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 gene therapy in subjects with DR with and without center-involved diabetic macular edema (CI-DME).

Part 1: For subjects with DR without CI-DME, approximately 100 participants who meet the inclusion/exclusion criteria will be enrolled into one of 5 cohorts. Participants will be randomized in Cohorts 1, 2, 4 and 5 to receive ABBV-RGX-314 or to be observed, and participants enrolled in Cohort 3 will receive ABBV-RGX-314. Cohort 1 will evaluate ABBV-RGX-314 Dose 1, Cohorts 2 and 3 will evaluate ABBV-RGX-314 Dose 2, and Cohorts 4 and 5 will evaluate ABBV-RGX-314 Dose 3. Following SCS ABBV-RGX-314 administration, participants in Cohorts 4 and 5 will receive a protocol-mandated post-procedure steroid regimen for 7 weeks. Participants who are randomized to be observed in Cohorts 1, 2, 4 and 5 will be offered ABBV-RGX-314 after completing the study.

Part 2: For subjects with DR with CI-DME, approximately 30 participants who meet the inclusion/exclusion criteria will be enrolled into one cohort (Cohort A). Participants will be randomized to receive ABBV-RGX-314 or Aflibercept Control. Cohort A will evaluate ABBV-RGX-314 Dose 4. Participants randomized to receive SCS ABBV-RGX-314 will receive a protocol-mandated course of steroid. Participants who are randomized to the Aflibercept Control arm will be offered ABBV-RGX-314 after completing the study.

Eligibility criteria: Part 1 (DR without CI-DME):

Inclusion Criteria:

* Patients 25-89 years of age with a diabetic retinopathy (DR) diagnosis of nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) secondary to diabetes mellitus Type 1 or 2 for which PRP or anti-VEGF injections can be safely deferred for at least 6 months
* HbA1c \< 12%.
* Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better).
* Prior history of CI-DME in the study eye is acceptable.
* Must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

* Neovascularization in the study eye from a cause other than DR.
* Presence of any active CI-DME.
* Active or history of retinal detachment in the study eye.
* Any evidence or documented history of PRP or retinal laser in the study eye.
* Patients who had a prior vitrectomy surgery.
* Women of childbearing potential.

Part 2 (DR with CI-DME):

Inclusion Criteria:

* Patients 25-89 years of age with diabetic retinopathy secondary to diabetes mellitus Type 1 or 2.
* HbA1c \< 12%
* Macular thickening secondary to DME involving the center of the fovea, CST on SD-OCT (≥ 325 μm)
* Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of 78-25 letters (approximate Snellen equivalent of 20/32 to 20/320)
* Participants must have demonstrated a meaningful response to anti-VEGF therapy.
* Must be willing and able to provide written, signed informed consent

Exclusion Criteria:

* Neovascularization in the study eye from a cause other than DR.
* Active or history of retinal detachment in the study eye.
* Any evidence or documented history of PRP or retinal laser in the study eye.
* Patients who had a prior vitrectomy surgery.
* Women of childbearing potential.

Note: Other inclusions/exclusions criteria apply.

Primary outcomes:
measure: Part 1: Proportion of participants achieving a 2-step or greater improvement in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography at Week 48
timeFrame: At Week 48
measure: Part 2: Mean change from baseline in Best Corrected Visual Acuity (BCVA) in the study eye at Week 54.
timeFrame: At Week 54
Secondary outcomes:
measure: Part 1: Proportion of participants achieving an improvement in DR in the study eye per the ETDRS DRSS on 4 widefield digital stereoscopic fundus photography.
timeFrame: At Week 4, Week 12, Week 24, and Week 36
measure: Part 1:Proportion of participants achieving a 0-step (no change) or greater improvement in DR in the study eye per the ETDRS DRSS on 4 widefield digital stereoscopic fundus photography.
timeFrame: At Week 4, Week 12, Week 24, Week 36, and Week 48
measure: Part 1:Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography.
timeFrame: At Week 4, Week 12, Week 24, Week 36, and Week 48
measure: Part 1: Proportion of participants in the NPDR and PDR subgroups at baseline achieving an improvement or worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography.
timeFrame: At Week 4, Week 12, Week 24, Week 36, and Week 48
measure: Part 1: Proportion of participants graded as proliferative diabetic retinopathy (PDR) in the study eye at baseline achieving regression to nonproliferative diabetic retinopathy (NPDR) in the study eye.
timeFrame: At Week 24, Week 36, and Week 48
measure: Part 1: Proportion of participants achieving a 0-step (no change) or greater improvement in DR in the study eye per the ETDRS-DRSS on 4-widefield digital stereoscopic fundus photography
timeFrame: At Week 54, Week 62, and Week 74 (Crossover (CO) participants)
measure: Part 1: Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography.
timeFrame: At Week 54, Week 62, and Week 74 (Crossover participants)
measure: Part 1: Mean change from baseline in the study eye in ETDRS-DRSS severity steps at Week 12, Week 24, Week 36, and Week 48 and (CO participants) change from Week 48 at Week 54, Week 62, and Week 74
timeFrame: Baseline to Week 12, Week 24, Week 36, and Week 48; Week 48 to Week 54, Week 62, and Week 74 (Crossover participants)
measure: Part 1: Incidences of overall and ocular AEs
timeFrame: Through Week 48; and through Week 74 (Crossover participants)
measure: Part 1: Vector shedding analysis in serum, urine, and tears
timeFrame: Through Week 48; and through Week 74 (Crossover participants)
measure: Part 1: Proportion of participants who experience ocular inflammation in the study eye following Suprachoroidal Space (SCS) ABBV-RGX-314 administration.
timeFrame: Through Week 48; and through Week 74 (Crossover participants)
measure: Part 1: Proportion of participants requiring any additional intervention in the study eye for ocular diabetic complications
timeFrame: Through Week 48 or Week 74 (Crossover participants)
measure: Part 1: Proportion of participants with any sight threatening ocular diabetic complications in the study eye based on duration of time to development of sight threatening ocular conditions
timeFrame: Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)
measure: Part 1:Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on number of treatments received and duration of time from intervention to first treatment per SOC
timeFrame: Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)
measure: Part 1: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on duration of time from study intervention to first treatment and proportion of participants requiring more than 1 treatment
timeFrame: Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)
measure: Part 1: Proportion of participants developing ocular diabetic complications in the study eye requiring surgical intervention per SOC based on duration of time from study intervention to surgical intervention
timeFrame: Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)
measure: Part 1: Aqueous ABBV-RGX-314 TP concentration at assessed time points
timeFrame: Through Week 48 or Week 74 (Crossover participants)
measure: Part 1: Serum ABBV-RGX-314 TP concentration at assessed time points
timeFrame: Through Week 48 or Week 74 (Crossover participants)
measure: Part 2: Mean change from baseline in BCVA in the study eye over time
timeFrame: Through Week 54
measure: Part 2: Proportion of participants with improved BCVA in the study eye over time
timeFrame: Through Week 54
measure: Part 2: Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography
timeFrame: At Week 14, Week 30, Week 38, and Week 54
measure: Part 2: Proportion of participants achieving an improvement in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography
timeFrame: At Week 14, Week 30, Week 38, and Week 54
measure: Part 2: Proportion of participants achieving a 0-step (no change) or greater improvement in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography
timeFrame: At Week 66 and Week 82 (Crossover participants)
measure: Part 2: Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4-widefield digital stereoscopic fundus photography
timeFrame: At Week 66 and Week 82 (Crossover participants)
measure: Part 2: Mean change from baseline in the study eye in ETDRS-DRSS severity steps at Week 22, Week 38, and Week 54 and (CO participants) change from Week 56 at Week 74 and Week 82
timeFrame: Baseline to Week 22, Week 38, and Week 54; Week 56 to Week 74 and Week 82 (Crossover participants)
measure: Part 2: Proportion of participants with an absence of CI-DME in the study eye
timeFrame: At Week 54
measure: Part 2: Incidences of overall and ocular AEs
timeFrame: Through Week 54 or Week 82 (Crossover participants)
measure: Part 2: Vector shedding analysis in serum, urine, and tears
timeFrame: Through Week 54 or Week 82 (Crossover participants)
measure: Part 2: Proportion of participants who experience ocular inflammation in the study eye following SCS ABBV-RGX-314 administration
timeFrame: Through Week 54 or Week 82 (Crossover participants)
measure: Part 2: Proportion of participants requiring any additional intervention in the study eye for ocular diabetic complications to Week 54 and (CO participants) Week 82
timeFrame: Through Week 54 or Week 82 (Crossover participants)
measure: Part 2: Proportion of participants with any sight threatening ocular diabetic complications in the study eye based on duration of time to development of sight-threatening ocular conditions
timeFrame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
measure: Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on number of treatments received and duration of time from study intervention to first treatment per SOC
timeFrame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
measure: Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on duration of time from study intervention to first treatment and proportion of participants requiring more than 1 treatment
timeFrame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
measure: Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring surgical intervention per SOC
timeFrame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
measure: Part 2: Mean change from baseline in CST in the study eye on SD OCT at Week 30 and Week 54
timeFrame: At Week 30 and Week 54
measure: Part 2: Mean change from Week 54 in CST in the study eye on SD OCT at Week 82 (Crossover participants)
timeFrame: At Week 82
measure: Part 2: Proportion of participants achieving a reduction in CST in the study eye on SD-OCT at Week 30 and Week 54
timeFrame: At Week 30 and Week 54
measure: Part 2: Aqueous ABBV-RGX-314 TP concentration at assessed time points
timeFrame: Through Week 54 or Week 82 (Crossover participants)
measure: Part 2: Serum ABBV-RGX-314 TP concentration at assessed time points
timeFrame: Through Week 54 or Week 82 (Crossover participants)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates Medical Group, Inc.
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical Group, Inc
state: California
city: Poway
country: United States
facility: Retinal Consultants San Diego
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Baltimore
country: United States
facility: Wilmer Eye Institute/Johns Hopkins University School of Medicine
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Teaneck
country: United States
facility: NJ Retina
state: New Jersey
city: Albuquerque
country: United States
facility: Vision Research Center Eye Associates of New Mexico
state: New Mexico
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Germantown
country: United States
facility: Charles Retina Institute, P.C.
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas, LLC
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: Burleson
country: United States
facility: Star Retina
state: Texas
city: The Woodlands
country: United States
facility: Retinal Consultants of Texas
state: Texas
Study officials:
References: