Neovascular Age-related Macular DegenerationPhase 2Z-AMDNCT04304755
Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (Z-AMD)
A Phase 2 study testing Zoledronic Acid 5 MG in 5 ML Injection in people with Neovascular Age-related Macular Degeneration, run by Oslo University Hospital at 2 sites in Norway.
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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascular Age-related Macular Degeneration
- What is being tested?
- Zoledronic Acid 5 MG in 5 ML Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesNorway
- Study dates
- 25 Oct 2021to 24 Jan 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Spesialistsenteret Pilestredet Park
Oslo, 0176
Oslo university hospital, Department of Ophthamology
Oslo, 0407
About this study
Official title: 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).
Read the 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.
- Being tested
- Zoledronic Acid 5 MG in 5 ML Injection, Placebos
- Keywords
- zoledronic acid, anti-VEGF, anti-vascular endothelial growth factor, adjuvant therapy, AMD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic Acid 5 MG in 5 ML InjectionDrug
Also called ZA
Zoledronic acid
PlacebosDrug
Also called NaCl
NaCl 0.9%
| Study group | Role | What they receive |
|---|---|---|
| Investigational Medical Product : Zoledronic acid | Experimental | Zoledronic acid 5 mg IV at baseline and after 26 weeks. Receives: Drug: Zoledronic Acid 5 MG in 5 ML Injection |
| Placebo: NaCl 0,9% | Placebo comparator | 100 ml 0.9% NaCl IV at baseline and after 26 weeks. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 52 weeks
Secondary outcomes (6)
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.
Measured: 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.
Measured: 52 weeks
Proportion of patients with refractory nAMD after 52 weeks.
Proportion of patients with refractory nAMD after 52 weeks.
Measured: 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).
Measured: 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
Measured: 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).
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start25 Oct 2021
- Primary completion24 Jan 2024
- Study completion24 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neovascular Age-related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Morten Carstens Moe, Oslo University Hospital
- Investigators
- Morten C Moe, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04304755
- Sponsor's protocol ID
- 2019/583
- Acronym
- Z-AMD
- Status last verified
- Apr 2024
- First submitted
- 23 Feb 2020
- Last updated
- 5 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Husum YS, Moe MC, Fagerland MW, Eriksen EF, Jorstad OK. Zoledronic acid as adjuvant therapy in neovascular age-related macular degeneration: a randomised controlled pilot study. BMJ Open Ophthalmol. 2024 Dec 25;9(1):e001964. doi: 10.1136/bmjophth-2024-001964.
PubMed 39721968
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (The Z-AMD Study): A Randomized Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT04304755
- Acronym / sponsor ID
- Z-AMD / 2019/583
- Keywords
- zoledronic acid, anti-VEGF, anti-vascular endothelial growth factor, adjuvant therapy, AMD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 24 Jan 2024 (actual)
- Study completion
- 24 Jan 2024 (actual)
- First posted
- 11 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Investigational Medical Product : Zoledronic acid | Experimental | Drug: Zoledronic Acid 5 MG in 5 ML InjectionZoledronic acid 5 mg IV at baseline and after 26 weeks. |
| Placebo: NaCl 0,9% | Placebo comparator | Drug: Placebos100 ml 0.9% NaCl IV at baseline and after 26 weeks. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic Acid 5 MG in 5 ML InjectionAlso: ZAZoledronic acid | Drug | Investigational Medical Product : Zoledronic acid |
| PlacebosAlso: NaClNaCl 0.9% | Drug | Placebo: NaCl 0,9% |
Primary outcome
Mean change from baseline in best-corrected visual acuity (BCVA) after 52 weeks.
Time frame: 52 weeks
To assess the change in best-corrected visual acuity measured by logMAR.
6 secondary outcomes
The number of anti-VEGF intravitreal injections given after 52 weeks
Time frame: 52 weeks
Number of patients with a change in BCVA of 0.3 logMAR or more after 52 weeks.
Time frame: 52 weeks
Proportion of patients with refractory nAMD after 52 weeks.
Time frame: 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).
Time frame: 52 weeks
Mean change from baseline in Central retinal thickness (CRT) after 52 weeks.
Time frame: 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).
Time frame: 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2024.
- Derived from this study: PubMed 39721968Husum YS, Moe MC, Fagerland MW, Eriksen EF, Jorstad OK. Zoledronic acid as adjuvant therapy in neovascular age-related macular degeneration: a randomised controlled pilot study. BMJ Open Ophthalmol. 2024 Dec 25;9(1):e001964. doi: 10.1136/bmjophth-2024-001964.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morten C Moe, MD, PhD principal investigator
Oslo University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zoledronic Acid 5 MG in 5 ML Injection in people with Neovascular Age-related Macular Degeneration, run by Oslo University Hospital at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change from baseline in best-corrected visual acuity (BCVA) after 52 weeks. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04304755, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2024; AzTrials last refreshed its copy on 8 Nov 2026.