Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (Z-AMD)

Overview

A PHASE IIA CLINICAL TRIAL OF ZOLEDRONIC ACID AS ADJUVANT THERAPY TO STANDARD ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR (ANTI-VEGF) TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (AMD)

Full Title of Study: “Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (The Z-AMD Study): a Randomized Clinical Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: March 2024

Interventions

  • Drug: Zoledronic Acid 4 MG in 5 ML Injection
    • Zoledronic acid
  • Drug: Placebos
    • NaCl 0.9%

Arms, Groups and Cohorts

  • Experimental: Zoledronic acid
    • Zoledronic acid 5 mg IV at baseline and after 24 weeks.
  • Placebo Comparator: NaCl
    • 100 ml 0.9% NaCl IV at baseline and after 24 weeks.

Clinical Trial Outcome Measures

Primary Measures

  • The number of anti-VEGF intravitreal injections given after 48 weeks.
    • Time Frame: After 48 weeks of treatment.
    • To assess the number of anti-VEGF injections needed during 48 weeks of treatment.

Secondary Measures

  • The number of anti-VEGF intravitreal injections given after 96 weeks.
    • Time Frame: After 96 weeks of treatment.
    • To assess the number of anti-VEGF injections needed during 96 weeks of treatment.
  • Mean change from baseline in best-corrected visual acuity (BCVA) after 48 weeks.
    • Time Frame: 48 weeks
    • To assess the change in best-corrected visual acuity measured by logMAR.
  • Mean change from baseline in best-corrected visual acuity (BCVA) after 96 weeks.
    • Time Frame: 96 weeks
    • To assess the change in best-corrected visual acuity measured by logMAR.
  • Number of patients with a change in BCVA of 0.3 logMAR or more after 48 weeks.
    • Time Frame: 48 weeks
    • Number of patients with a change in BCVA of 0.3 logMAR or more after 48 weeks.
  • Number of patients with a change in BCVA of 0.3 logMAR or more after 96 weeks.
    • Time Frame: 96 weeks
    • Number of patients with a change in BCVA of 0.3 logMAR or more after 96 weeks.
  • Proportion of patients on extended anti-VEGF injection interval (>4 weeks) after 48 weeks.
    • Time Frame: 48 weeks
    • Proportion of patients on extended anti-VEGF injection interval (>4 weeks) after 48 weeks.
  • Proportion of patients on extended anti-VEGF injection interval (>4 weeks) after 96 weeks.
    • Time Frame: 96 weeks
    • Proportion of patients on extended anti-VEGF injection interval (>4 weeks) after 96 weeks.
  • Proportion of patients reaching the Maximum anti-VEGF injection interval of 12 weeks after 48 weeks.
    • Time Frame: 48 weeks
    • Proportion of patients reaching the Maximum anti-VEGF injection interval of 12 weeks after 48 weeks.
  • Proportion of patients reaching the Maximum anti-VEGF injection interval of 12 weeks after 96 weeks.
    • Time Frame: 96 weeks
    • Proportion of patients reaching the Maximum anti-VEGF injection interval of 12 weeks after 96 weeks.
  • Mean change from baseline in Central retinal thickness (CRT) after 48 weeks.
    • Time Frame: 48 weeks
    • Mean change from baseline in Central retinal thickness (CRT) after 48 weeks.
  • Mean change from baseline in Central retinal thickness (CRT) after 96 weeks.
    • Time Frame: 96 weeks
    • Mean change from baseline in Central retinal thickness (CRT) after 96 weeks.
  • Proportion of patients with treatment-resistant AMD.
    • Time Frame: 48 weeks and 96 weeks
    • Proportion of patients with treatment-resistant AMD.
  • EQ 5D score (ranging from 0-1; 0 designates “perfect health” and NEI-VFQ-25 score (ranging from 0 to 100 where 100 reflects best vision-specific health).
    • Time Frame: Baseline, 48 weeks and 96 weeks
    • EQ 5D score (ranging from 0-1; 0 designates “perfect health” and NEI-VFQ-25 score (ranging from 0 to 100 where 100 reflects best vision-specific health).
  • Proportion of patients experiencing adverse events of special interest (ESI): osteonecrosis of the jaw or atypical femoral fracture, endophthalmitis or orbital, scleral, or serious intraocular inflammation (grade 4 aqueous cells/FLARE).
    • Time Frame: 48 weeks and 96 weeks
    • Proportion of patients experiencing adverse events of special interest (ESI): osteonecrosis of the jaw or atypical femoral fracture, endophthalmitis or orbital, scleral, or serious intraocular inflammation (grade 4 aqueous cells/FLARE).

Participating in This Clinical Trial

Inclusion Criteria

Active, treatment-naïve neovascular AMD in the study eye, intraretinal or subretinal fluid involving the fovea centre on optical coherence tomography (OCT), and evidence of choroidal neovascularization on fluorescein angiography (FA) and/or OCT angiography (OCT-A). 1. Age ≥50 years 2. Best-corrected visual acuity (BCVA) between 0.1 and 1.0 logMAR 3. Menopausal for at least one year 4. Subjects must give written informed consent before any study related procedures are performed Exclusion Criteria:

1. Lesions comprising more than 50% blood or fibrosis involving the fovea centre 2. Polypoidal choroidal vasculopathy (PCV) – indocyanine green (ICG) angiography is performed at the discretion of the investigator on clinical suspicion of PCV 3. Presence of other ocular disease causing concurrent vision loss 4. Presence of ocular disease making intravitreal treatment contraindicated (e.g. current ocular or periocular infection, active uveitis or uncontrolled glaucoma/intraocular pressure ≥ 25 mmHg) 5. Systemic anti-vascular endothelial growth factor (anti-VEGF) or bisphosphonate treatment within one year preceding the initial study treatment 6. Confirmed or suspected active malignancy 7. Other factors (i.e. lack of cooperation) that, in the opinion of the investigator, can interfere with the study protocol 8. Known or suspected hypersensitivity to any of the trial products 9. Hypocalcemia (total Ca < 2.15 mmol/L) 10. Renal impairment (estimated ClCR < 35 ml/min).

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Oslo University Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Morten Carstens Moe, MD, Professor in Ophthalmology – Oslo University Hospital
  • Overall Official(s)
    • Morten C Moe, MD, PhD, Principal Investigator, Oslo University Hospital
  • Overall Contact(s)
    • Morten C Moe, MD, PhD, +47 23015166, mortmo@ous-hf.no

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