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

Sponsor

Oslo University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04304755

Collaborator

(none)

Enrollment

Locations

Arms

22.6

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration	Drug: Zoledronic Acid 5 MG in 5 ML Injection Drug: Placebos	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 25, 2021

Anticipated Primary Completion Date :

Sep 13, 2023

Anticipated Study Completion Date :

Sep 13, 2023

Arms and Interventions

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

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:

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

Outcome Measures

Primary Outcome Measures

Mean change from baseline in best-corrected visual acuity (BCVA) after 52 weeks. [52 weeks]
To assess the change in best-corrected visual acuity measured by logMAR.

Secondary Outcome Measures

The number of anti-VEGF intravitreal injections given after 52 weeks [52 weeks]
To assess the number of anti-VEGF injections needed during 52 weeks of treatment.
Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks. [52 weeks]
Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.
Proportion of patients with refractory nAMD after 52 weeks. [52 weeks]
Proportion of patients with refractory nAMD after 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). [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).
Mean change from baseline in Central retinal thickness (CRT) after 52 weeks. [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
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]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).
Age ≥50 years
Best-corrected visual acuity (BCVA) between 0.1 and 1.0 logMAR
Menopausal for at least one year
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.
Subjects must give written informed consent before any study related procedures are performed

Exclusion Criteria:

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