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

NCT02398500 | Terminated Phase 1

• 2 other identifiers: LMG324-22012014-005214-37
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Age-related Macular Degeneration (AMD)

Keywords

First-in-human; anti-VEGF; neovascular AMD (nvAMD)

Outcome Measures

Primary Outcomes (1)

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

  Baseline, Day 85

Secondary Outcomes (17)

• Percentage of LMG324-treated subjects with no identified SoC treatment need up to and including Day 85

  Up to Day 85

• Best Corrected Visual Acuity (BCVA)

  Up to Day 169

• Central subfield thickness total (CSFTtot)

  Up to Day 169

• Central subfield thickness neuro-retina (CFSTnr)

  Up to Day 169

• Lesion thickness

  Up to Day 169

Study Arms (3)

LMG324

EXPERIMENTAL

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

Biological: LMG324

LMG324 + sham

EXPERIMENTAL

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

Biological: LMG324; Biological: Sham

Lucentis + sham

ACTIVE COMPARATOR

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

Biological: Ranibizumab 0.5 mg; Biological: Sham

Interventions

LMG324 BIOLOGICAL

IVT injection

LMG324; LMG324 + sham

Ranibizumab 0.5 mg BIOLOGICAL

IVT injection

Also known as: Lucentis®

Lucentis + sham

Sham BIOLOGICAL

Fake injection used for masking purposes

LMG324 + sham; Lucentis + sham

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alcon Research: lead
• Novartis Institutes for BioMedical Research: collaborator

Study Sites (1)

Call Alcon Call Center for Trial Locations

Fort Worth, Texas, 76134, United States

Location

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Scientist I, NIBR

  Alcon Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2015
• First Posted: March 25, 2015
• Study Start: July 22, 2015
• Primary Completion: February 29, 2016
• Study Completion: May 20, 2016
• Last Updated: June 5, 2019

Record last verified: 2019-06

Locations

US (1)