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INFINITY: ADVM-022 Intravitreal Gene Therapy for DME

Sponsor
Adverum Biotechnologies, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04418427
Collaborator
(none)
36
Enrollment
14
Locations
3
Arms
30.1
Anticipated Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 2, Multi-Center, Randomized, Double-Masked*, Active Controlled Study of ADVM-022 (AAV.7m8-aflibercept) in Subjects with Diabetic Macular Edema [INFINITY]

*sponsor unmasked for enhanced safety monitoring as of May 2021

Condition or Disease Intervention/Treatment Phase
  • Biological: 6E11 vg/eye of ADVM-022
  • Biological: 2E11 vg/eye of ADVM-022
  • Biological: Aflibercept
 Phase 2

Detailed Description

ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of serious retinal vascular diseases including Diabetic Macular Edema (DME). DME affects up to 10% of people with diabetes is caused by fluid accumulation in the macula and is the most frequent cause of sight loss in people with diabetic retinopathy. Available therapies for treating DME include laser and anti-vascular endothelial growth factor (anti-VEGF) drugs. Anti-VEGFs require frequent and long-term intravitreal (IVT) injections to achieve and maintain efficacy. A one-time IVT administration of ADVM-022 has the potential to treat DME by providing durable expression of an anti-VEGF protein (aflibercept) to limit abnormal blood vessel leakage. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment, progression of disease and subsequent vision loss in patients with DME.

In INFINITY, approximately 33 eligible subjects will be randomly assigned to receive one of the two doses of ADVM-022, or, assigned to the control arm to receive a sham ocular injection with a preceding aflibercept injection. Subjects who are assigned to receive ADVM-022 will be further randomized to receive a preceding aflibercept or sham ocular injection. All subjects will be assessed regularly and will receive additional aflibercept injections should DME disease activity progress.

The primary objective is to assess the durability of a single intravitreal (IVT) injection of ADVM-022. All subjects will be followed for 96 weeks after randomization.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
From May 2020 through April 2021: Double-masked study Subjects, outcomes assessors and the designated masked study personnel will be masked to subject's treatment assignment throughout the study. There must be a minimum of two physicians per site to fulfill the masking requirements of the study. A masked and unmasked investigator are required to be present for administration of the preceding dose of aflibercept or sham and following dose of ADVM-022 or sham visits, thereafter only the masked investigator is required to be present. Starting May 2021: Open label study, study was unmasked for enhance safety monitoring.
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multi-Center, Randomized, Double-Masked, Active Controlled Study of ADVM-022 (AAV.7m8-aflibercept) in Subjects With Diabetic Macular Edema [INFINITY]
Actual Study Start Date :
May 28, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

6E11 vg/eye ADVM-022 +/- aflibercept 2mg IVT

Biological: 6E11 vg/eye of ADVM-022
ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
Other Names:
  • AAV.7m8-aflibercept

    • Biological: Aflibercept
    Commercially available Active Comparator
    Other Names:
  • Eylea

    		•
    Experimental: 2

    2E11 vg/eye ADVM022 +/- aflibercept 2mg IVT

    Biological: 2E11 vg/eye of ADVM-022
    ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
    Other Names:
  • AAV.7m8-aflibercept

    • Biological: Aflibercept
    Commercially available Active Comparator
    Other Names:
  • Eylea

    		•
    Active Comparator: 3

    Aflibercept 2mg IVT

    Biological: Aflibercept
    Commercially available Active Comparator
    Other Names:
  • Eylea

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to worsening of DME disease activity in the study eye. [96 weeks]

      Time to worsening of DME disease activity in the study eye.

    Secondary Outcome Measures

    1. Incidence and severity of ocular and non-ocular adverse events (AEs) [96 weeks]

      Incidence and severity of ocular and non-ocular adverse events (AEs)

    2. Change from Baseline in central subfield thickness (CST) and macular volume over time measured by SD-OCT [96 weeks]

      Change from Baseline in central subfield thickness (CST) and macular volume over time measured by SD-OCT

    3. Change from Baseline in BCVA over time [96 weeks]

      Change from Baseline in BCVA over time

    4. Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study [96 weeks]

      Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study

    5. Incidence of improvement in DRSS score over time [96 weeks]

      Incidence of improvement in DRSS score over time

    6. Incidence of worsening in DRSS score over time [96 weeks]

      Incidence of worsening in DRSS score over time

    7. Occurrence of vision threatening complication over time [96 weeks]

      Occurrence of vision threatening complication over time

    8. Incidence of CST <300 μm over time through Week 48 [96 weeks]

      Incidence of CST <300 μm over time through Week 48

    9. Incidence of clinically significant findings via physical examinations, ocular examinations, imaging, and laboratory evaluation [96 weeks]

      Incidence of clinically significant findings via physical examinations, ocular examinations, imaging, and laboratory evaluation

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age ≥ 18

    • Type 1 or Type 2 diabetes mellitus

    • Willing and able to provide informed consent

    • Vision impairment due to center involving diabetic macular edema

    Exclusion Criteria:

    • Uncontrolled diabetes defined as HbA1C >10%, or history of diabetic ketoacidosis within 3 months prior to randomization; or subjects who, within the last 3 months, initiated intensive insulin treatment (a pump or multiple daily injection) or plan to do so in the next 3 months.

    • Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months

    • Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg

    • Known severe renal impairment

    • High risk Proliferative Diabetic Retinopathy

    • History of retinal disease in the study eye other than diabetic retinopathy

    • History of retinal detachment (with or without repair) in the study eye

    • History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye

    • Any prior focal or grid laser photocoagulation or any prior PRP in the study eye

    • Current or planned pregnancy or breastfeeding

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Adverum Clinical Site Phoenix Arizona United States 85014
    2 Adverum Clinical Site Bakersfield California United States 93309
    3 Adverum Clinical Site Beverly Hills California United States 90211
    4 Adverum Clinical Site Golden Colorado United States 80401
    5 Adverum Clinical Site Deerfield Beach Florida United States 33064
    6 Adverum Clinical Site Reno Nevada United States 89502
    7 Adverum Clinical Site Philadelphia Pennsylvania United States 19107
    8 Adverum Clinical Site West Columbia South Carolina United States 29169
    9 Adverum Clinical Site Nashville Tennessee United States 37203
    10 Adverum Clinical Site Abilene Texas United States 79606
    11 Adverum Clinical Site Austin Texas United States 78705
    12 Adverum Clinical Site Houston Texas United States 77030
    13 Adverum Clinical Site The Woodlands Texas United States 77384
    14 Adverum Clinical Site Arecibo Puerto Rico 00612

    Sponsors and Collaborators

    • Adverum Biotechnologies, Inc.

    Investigators

    • Study Chair: INFINITY Medical Monitor, MD, Adverum Biotechnologies, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Adverum Biotechnologies, Inc.
    ClinicalTrials.gov Identifier:
    NCT04418427
    Other Study ID Numbers:
    • ADVM-022-04
    First Posted:
    Jun 5, 2020
    Last Update Posted:
    Jan 11, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Adverum Biotechnologies, Inc.
    ADVM-022
    ADVM-022-04
    AAV.7m8
    Anti-VEGF therapy
    Blindness
    INFINITY
    Gene therapy
    Aflibercept (Eylea)
    Retinal Diseases
    Eye Diseases
    AAV Vector
    Adverum
    DME
    Diabetic macular edema
    Diabetic eye disease
    Diabetic retinopathy
    DR
    AAV.7m8-aflibercept
    Additional relevant MeSH terms:
    Macular Edema
    Retinal Diseases
    Diabetic Retinopathy
    Edema
    Aflibercept

    Study Results

    No Results Posted as of Jan 11, 2022