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

University of Oslo (UIO)

Status and phase: Completed; Phase 2

Conditions: Neovascular Age-related Macular Degeneration

Treatments: Drug: Placebos; Drug: Zoledronic Acid 5 MG in 5 ML Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT04304755

2019/583

Details and patient eligibility

About

A pilot study of zoledronic acid as adjuvant therapy to standard anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (AMD).

Full description

This is a one-year, randomized, controlled pilot study. A total of 40 treatment-naïve nAMD patients will be allocated 1:1 to receive an intravenous infusion of either zoledronic acid (ZA) 5 mg or placebo at baseline and after 26 weeks as adjuvant therapy to intravitreal anti-VEGF injections in accordance with a treat and extend algorithm; bevacizumab is the first-line treatment, and refractory eyes are converted to aflibercept.

The participants will be recruited among patients admitted to the Department of Ophthalmology at Oslo University Hospital (OUH). The department is the largest provider of retinal care in Norway and serves a local community of almost one million people, which makes it well-suited for recruitment. Administration of ZA or placebo will take place at Pilestredet Park Specialist Centre, an endocrinology clinic in Oslo with particular interest in treatment of osteoporosis. The Clinical Trial Unit at OUH will monitor the study.

Enrollment: 40 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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).
2. Age ≥50 years
3. Best-corrected visual acuity (BCVA) between 0.1 and 1.0 logMAR
4. Menopausal for at least one year
5. Only one eye per patient will be recruited for the study. If both eyes are eligible for the study, the eye with the wors best-corrected Visual acuity (BCVA) will be selected as the study eye.
6. 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Investigational Medical Product : Zoledronic acid

Experimental group

Description:

Zoledronic acid 5 mg IV at baseline and after 26 weeks.

Treatment:

Drug: Zoledronic Acid 5 MG in 5 ML Injection

Placebo: NaCl 0,9%

Placebo Comparator group

Description:

100 ml 0.9% NaCl IV at baseline and after 26 weeks.

Treatment:

Drug: Placebos