Safety and Efficacy of AM712 in Patients with NAMD

A Prospective, Multi-Center, Open-label, Sequential, Multiple Ascending-Dose and High Concentration Cohorts Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AM712 Following Intravitreal Administration in Patients with Neovascular Age-related Macular Degeneration.

The purpose of this Phase 1 study is comprised of multiple ascending-dose component (Part 1) and high concentration component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age- related macular degeneration (nAMD).

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Biological: AM712(ASKG712)

Detailed Description

The Part 1 of study is a multicenter, open-label, sequentially, multiple ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in subjects with nAMD.

Subjects will be sequentially enrolled into different dose-level cohorts following the traditional "3+3" design until the maximally tolerated dose (MTD) or the maximally administered dose (MAD) has been reached.

The Part 2 of study is a multicenter, open-label, sequential study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in treatment-naïve patients with nAMD.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Poway, California, United States, 92064
      • Retina Consultants San Diego
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina
  • Florida
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Retina Research Institute at New England Retina Consultants
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina, PC
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects with 50 years of age or older
2. Active sub-foveal CNV lesion secondary to nAMD including juxta or extra-foveal lesions that partially affect the fovea
3. The area of CNV must occupy at least 50% of total lesion
4. Total lesion area ≤ 12 DA
5. ETDRS BCVA letter score measured at screening and baseline
6. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging in study eye

Exclusion Criteria:

1. Any previous systemic anti-VEGF treatment
2. Any systemic treatment or therapy to treat neovascular AMD
3. Continuous use of systemic corticosteroids
4. Diseases that affect intravenous injection and venous blood sampling
5. Presence of CNV due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic myopia in study eye
6. History or any concurrent ocular condition which, in opinion of investigator, could either confound interpretation of efficacy and safety of IP or require medical or surgical intervention.
7. The area of fibrosis occupies ≥ 50% of total lesion area in study eye
8. Evidence of myopia degeneration, diagnosis supported by the axial length examination in study eye
9. History or any concurrent macular abnormality other than AMD in study eye
10. Current vitreous hemorrhage or history of vitreous hemorrhage in study eye
11. History of recurrent inflammation in study eye
12. History of treatment for nAMD
13. Subject having out of range laboratory values defined as:

ALT or AST > 2 x ULN, total bilirubin > 1.5 x ULN Serum creatinine > 1.5 x ULN, BUN > 2 x ULN HbA1c > 7.5% at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I- All; Subjects with neovascular AMD	Biological: AM712(ASKG712); AM712 is a recombinant anti-VEGF humanized monoclonal antibody and Ang-2 antagonist peptide fusion protein, which has high specificity for the binding of VEGF-A and Ang-2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ocular adverse events (AEs) of the study eyes	To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)	252 days
Incidence of non-ocular AEs	To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)	252 days
Any relevant safety observations derived from BCVA	To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)	252 days
Any relevant safety observations derived from SD-OCT	To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)	252 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in central subfield thickness as assessed by SD-OCT	To evaluate the efficacy of AM712 in Subjects with nAMD	252 days
Proportion of patients with no intraretinal fluid, subretinal fluid, or pigment epithelial detachment as assessed by SD-OCT	To evaluate the efficacy of AM712 in Subjects with nAMD	252 days
Mean change from baseline in BCVA (ETDRS)	To evaluate the efficacy of AM712 in Subjects with nAMD	252 days
Proportion of patients gaining ≥ 15 letters from baseline BCVA	To evaluate the efficacy of AM712 in Subjects with nAMD	252 days

Collaborators and Investigators

• Sponsor: AffaMed Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): November 4, 2024
• Study Completion (Actual): November 4, 2024

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 7, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: AM712E1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No