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Age-related Macular Degeneration (AMD)Phase 1/2NCT02398500

Safety Tolerability and Efficacy of Intravitreal LMG324 in the Treatment of Neovascular Age-Related Macular Degeneration

A Phase 1/2 study testing LMG324 and Ranibizumab 0.5 mg in people with Age-related Macular Degeneration (AMD), run by Alcon Research at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this first-in-human study is to evaluate the safety and tolerability of single ascending doses of LMG324 to determine the maximum tolerated dose (MTD) in neovascular age-related macular degeneration (nvAMD) subjects. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Age-related Macular Degeneration (AMD)
What is being tested?
LMG324 and Ranibizumab 0.5 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
1 siteUnited States
Study dates
22 Jul 2015to 20 May 2016
Phase
Phase 1/2
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

  • Must give written informed consent, be able to make the required study visits and follow instructions.
  • Best corrected visual acuity (BCVA) of 34 letters (approximately 20/200 Snellen or better) in the non-study eye.
  • SAD population only:
  • Subject's study eye must have a choroidal neovascularization (CNV) lesion due to age-related macular degeneration (AMD), either treatment naïve or previously treated, that can be expected to benefit, in the opinion of the investigator, from anti-vascular endothelial growth factor (anti-VEGF) therapy.
  • Previously treated eyes must have a history of least 3 administrations of any intravitreal (IVT) anti-VEGF therapeutic for the treatment of CNV with the last injection administered ≥ 1 month prior to the planned administration of the study drug.
  • Enrollment expansion population only
  • Subject's study eye must have untreated and active CNV lesion due to AMD.
  • BCVA, between 73 - 23 letters, inclusive (approximate Snellen equivalent 20/40 - 20/320) in the study eye.

Who cannot join

  • SAD and enrollment expansion population
  • Both eyes: any active ocular or periocular infection or active intraocular inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis).
  • Study eye: current vitreous hemorrhage or a history of rhegmatogenous retinal detachment.
  • Study eye: uncontrolled glaucoma (intraocular pressure [IOP] >25 mmHg on medication or according to Investigator's judgment).
  • SAD population only
  • Presence of any contraindications, in the Investigator's opinion, to IVT anti-VEGF therapeutic administration.
Show all 13Show fewer
  • Enrollment expansion population only
  • Study eye: subject has received any approved or investigational treatment for exudative (wet) AMD other than vitamin supplements.
  • Study eye: any current or history of macular or retinal disease other than exudative AMD
  • Study eye: serous pigment epithelial detachment (PED) under the foveal center or retinal pigment epithelium (RPE) tear/rip.
  • Study eye: any concurrent intraocular condition (eg, cataract, diabetic retinopathy) that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study.
  • Study eye: other ocular diseases that, in the opinion of the Investigator, can compromise the visual acuity
  • Study eye: Surgery, as specified in the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Call Alcon Call Center for Trial Locations

    Fort Worth, Texas, 76134

Other trials in United States

About this study

Official title: An Open-label Single Ascending Dose and Randomized Double-Masked, Ranibizumab Controlled, Safety, Tolerability, and Efficacy Study of Intravitreal LMG324 in Subjects With Neovascular Age-Related Macular Degeneration

The purpose of this first-in-human study is to evaluate the safety and tolerability of single ascending doses of LMG324 to determine the maximum tolerated dose (MTD) in neovascular age-related macular degeneration (nvAMD) subjects. Enrollment will be expanded at a safe and tolerated dose in treatment naïve nvAMD subjects to compare a single intravitreal (IVT) dose of LMG324 to ranibizumab 0.5 mg administered every 4 weeks for change from baseline in best-corrected visual acuity (BCVA) at Week 12 (Day 85).

Read the detailed description

The study will start with a single dose ascending (SAD) phase. LMG324 will be administered on Day 1 with no further treatment until implementation of standard of care (SoC) therapy. SoC therapy is ranibizumab 0.5 mg administered per label. Dose groups will be implemented sequentially to allow for safety review between the current and subsequent dose group. All treatments will be open-label, including ranibizumab used as SoC therapy.

In the enrollment expansion phase, subjects randomized to LMG324 arm will receive a single LMG324 IVT injection on Day 1 followed by sham (fake) IVT injections until implementation of SoC therapy. After implementation, SoC therapy will be applied monthly with sham injections applied at the interim planned visits. The enrollment expansion phase may start at a selected dose level whilst the dose escalation phase is still ongoing.

Being tested
LMG324, Ranibizumab 0.5 mg, Sham
Keywords
First-in-human, anti-VEGF, neovascular AMD (nvAMD)
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LMG324Biological

    IVT injection

  • Ranibizumab 0.5 mgBiological

    Also called Lucentis®

    IVT injection

  • ShamBiological

    Fake injection used for masking purposes

Study groups in NCT02398500
Study groupRoleWhat they receive
LMG324ExperimentalSAD: LMG324 administered as a single IVT injection in 1 eye (study eye) in 1 of 4 doses, with 15-day follow-up
Receives: Biological: LMG324
LMG324 + shamExperimentalExpansion: LMG324 administered as a single IVT injection in 1 eye (study eye), followed by sham injections, until implementation of SoC therapy as specified in the protocol, for 24 weeks
Receives: Biological: LMG324; Biological: Sham
Lucentis + shamActive comparatorExpansion: Ranibizumab 0.5 mg administered as monthly IVT injections in 1 eye (study eye) with interim sham injections, for 24 weeks
Receives: Biological: Ranibizumab 0.5 mg; Biological: Sham

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean change from baseline in best corrected visual acuity (BCVA) at Day 85

    Measured: Baseline, Day 85

Secondary outcomes (17)
  1. Percentage of LMG324-treated subjects with no identified SoC treatment need up to and including Day 85

    Measured: Up to Day 85

  2. Best Corrected Visual Acuity (BCVA)

    Measured: Up to Day 169

  3. Central subfield thickness total (CSFTtot)

    Measured: Up to Day 169

  4. Central subfield thickness neuro-retina (CFSTnr)

    Measured: Up to Day 169

  5. Lesion thickness

    Measured: Up to Day 169

  6. Subretinal fluid with foveal involvement (SRFfi) thickness

    Measured: Up to Day 169

  7. Retinal pigment epithelial detachment with foveal involvement (PEDfi) thickness

    Measured: Up to Day 169

  8. Area of lesion (associated with CNV)

    Measured: Up to Day 169

  9. Area of CNV within a lesion

    Measured: Up to Day 169

  10. Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

    Measured: Up to Day 169

  11. Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

    Measured: Up to Day 169

  12. Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)

    Measured: Up to Day 169

  13. Maximum observed maximum plasma concentration (Cmax)

    Measured: Up to Day 169

  14. Time to reach the maximum observed plasma concentration (Tmax)

    Measured: Up to Day 169

  15. Observed maximum plasma concentration following drug administration, by dose (Cmax/D)

    Measured: Up to Day 169

  16. Area under the plasma concentration-time curve divided by dose (AUC/D)

    Measured: Up to Day 169

  17. Frequency of subjects with anti-LMG324 antibodies

    Measured: Up to Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2015 (estimated)
  2. Study start22 Jul 2015
  3. Primary completion29 Feb 2016
  4. Study completion20 May 2016

Why it stopped: Management decision

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02398500
Sponsor's protocol ID
LMG324-2201
Other IDs
2014-005214-37, 2014
Status last verified
Jun 2019
First submitted
20 Mar 2015
Last updated
5 Jun 2019
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LMG324 and Ranibizumab 0.5 mg in people with Age-related Macular Degeneration (AMD), run by Alcon Research at 1 site in United States.

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 8 inclusion and 13 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: stopped early, as of the sponsor's last update on 5 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 was stopped early (reason given: Management decision). Results are not available in the source record.

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) at Day 85 (time frame: Baseline, Day 85). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 Jun 2019.

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