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

Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (The Z-AMD Study): A Randomized Controlled Pilot Study

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).

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Zoledronic Acid 5 MG in 5 ML Injection; Drug: Placebos

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Morten C Moe, MD, PhD; Phone Number: +47 23015166; Email: mortmo@ous-hf.no
• Study Contact Backup: Name: Øystein K Jørstad, MD; Phone Number: +47 22118545; Email: oeyjoe@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway, 0176
    • Spesialistsenteret Pilestredet Park
  • Oslo, Norway, 0407
    • Oslo university hospital, Department of Ophthamology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Medical Product : Zoledronic acid; Zoledronic acid 5 mg IV at baseline and after 26 weeks.	Drug: Zoledronic Acid 5 MG in 5 ML Injection; Zoledronic acid; Other Names: ZA
Placebo Comparator: Placebo: NaCl 0,9%; 100 ml 0.9% NaCl IV at baseline and after 26 weeks.	Drug: Placebos; NaCl 0.9%; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in best-corrected visual acuity (BCVA) after 52 weeks.	To assess the change in best-corrected visual acuity measured by logMAR.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of anti-VEGF intravitreal injections given after 52 weeks	To assess the number of anti-VEGF injections needed during 52 weeks of treatment.	52 weeks
Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.	Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.	52 weeks
Proportion of patients with refractory nAMD after 52 weeks.	Proportion of patients with refractory nAMD after 52 weeks.	52 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).	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).	52 weeks
Mean change from baseline in Central retinal thickness (CRT) after 52 weeks.	Mean change from baseline in Central retinal thickness (CRT) after 52 weeks.To assess the proportion of patients with a considerable change in visual function	52 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).	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).	52 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Morten C Moe, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): January 24, 2024
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: February 23, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: adjuvant therapy; AMD; anti-VEGF; anti-vascular endothelial growth factor; zoledronic acid
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 2019/583

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No