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

NCT ID: NCT02398500

Last Updated: 2019-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-22
• Study Completion Date: 2016-05-20

Brief 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. 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).

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.

Conditions

Age-related Macular Degeneration (AMD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

LMG324

SAD: LMG324 administered as a single IVT injection in 1 eye (study eye) in 1 of 4 doses, with 15-day follow-up

Group Type: EXPERIMENTAL

LMG324

Intervention Type: BIOLOGICAL

IVT injection

LMG324 + sham

Expansion: 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

Group Type: EXPERIMENTAL

LMG324

Intervention Type: BIOLOGICAL

IVT injection

Sham

Intervention Type: BIOLOGICAL

Fake injection used for masking purposes

Lucentis + sham

Expansion: Ranibizumab 0.5 mg administered as monthly IVT injections in 1 eye (study eye) with interim sham injections, for 24 weeks

Group Type: ACTIVE_COMPARATOR

Ranibizumab 0.5 mg

Intervention Type: BIOLOGICAL

IVT injection

Sham

Intervention Type: BIOLOGICAL

Fake injection used for masking purposes

Interventions

LMG324

IVT injection

Intervention Type: BIOLOGICAL

Ranibizumab 0.5 mg

IVT injection

Intervention Type: BIOLOGICAL

Sham

Fake injection used for masking purposes

Intervention Type: BIOLOGICAL

Other Intervention Names

Lucentis®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

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.

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Institutes for BioMedical Research

OTHER

Sponsor Role: collaborator

Alcon Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Scientist I, NIBR

Role: STUDY_DIRECTOR

Alcon Research

Locations

Call Alcon Call Center for Trial Locations

Fort Worth, Texas, United States

Countries

United States

Other Identifiers

2014-005214-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LMG324-2201

Identifier Type: -

Identifier Source: org_study_id