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

Neovascular Age-related Macular Degeneration Clinical Trial

— Z-AMD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04304755
• Other study ID #: 2019/583
• Status: Completed
• Phase: Phase 2
• Start date: October 25, 2021
• Est. completion date: January 24, 2024

Study information

• Verified date: April 2024
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 24, 2024
• Est. primary completion date: January 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

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

Locations

Country	Name	City	State
Norway	Oslo university hospital, Department of Ophthamology	Oslo
Norway	Spesialistsenteret Pilestredet Park	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Proportion of patients with refractory nAMD after 52 weeks.	Proportion of patients with refractory nAMD after 52 weeks.	52 weeks
Secondary	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
Secondary	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
Secondary	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