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

Primary Purpose

Neovascular Age-related Macular Degeneration

Status

Active

Phase

Phase 2

Locations

Norway

Study Type

Interventional

Intervention

Zoledronic Acid 5 MG in 5 ML Injection

Placebos

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration focused on measuring zoledronic acid, anti-VEGF, anti-vascular endothelial growth factor, adjuvant therapy, AMD

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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).

Sites / Locations

Spesialistsenteret Pilestredet Park
Oslo university hospital, Department of Ophthamology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Investigational Medical Product : Zoledronic acid

Placebo: NaCl 0,9%

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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).

Full Information

NCT ID

NCT04304755

First Posted

February 23, 2020

Last Updated

March 17, 2023

Sponsor

Oslo University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04304755

Brief Title

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

Acronym

Z-AMD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 25, 2021 (Actual)

Primary Completion Date

February 29, 2024 (Anticipated)

Study Completion Date

February 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oslo University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neovascular Age-related Macular Degeneration

Keywords

zoledronic acid, anti-VEGF, anti-vascular endothelial growth factor, adjuvant therapy, AMD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Investigational Medical Product : Zoledronic acid

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo: NaCl 0,9%

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Zoledronic Acid 5 MG in 5 ML Injection

Other Intervention Name(s)

Intervention Description

Zoledronic acid

Intervention Type

Drug

Intervention Name(s)

Placebos

Other Intervention Name(s)

NaCl

Intervention Description

NaCl 0.9%

Primary Outcome Measure Information:

Title

Mean change from baseline in best-corrected visual acuity (BCVA) after 52 weeks.

Description

To assess the change in best-corrected visual acuity measured by logMAR.

Time Frame

52 weeks

Secondary Outcome Measure Information:

Title

The number of anti-VEGF intravitreal injections given after 52 weeks

Description

To assess the number of anti-VEGF injections needed during 52 weeks of treatment.

Time Frame

52 weeks

Title

Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.

Description

Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.

Time Frame

52 weeks

Title

Proportion of patients with refractory nAMD after 52 weeks.

Description

Proportion of patients with refractory nAMD after 52 weeks.

Time Frame

52 weeks

Title

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).

Description

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

52 weeks

Title

Mean change from baseline in Central retinal thickness (CRT) after 52 weeks.

Description

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

Time Frame

52 weeks

Title

Description

Time Frame

52 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Morten C Moe, MD, PhD

Organizational Affiliation

Oslo University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Spesialistsenteret Pilestredet Park

City

Oslo

ZIP/Postal Code

0176

Country

Norway

Facility Name

Oslo university hospital, Department of Ophthamology

City

Oslo

ZIP/Postal Code

0407

Country

Norway

12. IPD Sharing Statement

Learn more about this trial

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

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