A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of IVT MHU650 in Macular Edema Patients

A First-in-human, Open-label, Single Ascending Dose Study to Assess Safety and Tolerability of Intravitreal MHU650 in Participants With Macular Edema From Diabetic Macular Edema (DME), Neovascular Age-related Macular Degeneration (nAMD), or Retinal Vein Occlusion (RVO)

This was an open-label, multi-center, FIH study with a single ascending dose (SAD) design that assessed the safety, tolerability and pharmacokinetics (PK) of a single IVT dose of MHU650 in up to 24 participants with macular edema.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema; Macular Edema; Retinal Vein Occlusion; Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: MHU650

Detailed Description

A total of up to 4 cohorts were planned to be enrolled, with an additional lower or intermediate cohort of participants. First to third generation Japanese participants could be enrolled in all cohorts but were not required to be enrolled. The screening period for this study will be up to 60 days. A single dose of MHU650 intravitreal injection will be administered at Baseline / Day 1 in the study eye. The follow up period will last until Day 60 / end of study (EOS). A post study safety phone contact call will occur 30 days after the EOS visit.

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

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Novartis Investigative Site
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Novartis Investigative Site
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78793
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Patients with macular edema in at least one eye, including those with focal or diffuse diabetic macular edema (DME), neovascular age-related macular degeneration (nAMD), or retinal vein occlusion (RVO). In the opinion of the investigator, the decrease in vision in the study eye must be due to macular edema.
• Early Treatment Diabetic Retinopathy (ETDRS) letter score in the study eye must equal to or worse than 60 letters (approximately Snellen equivalent of 20/63) but better than 14 letters (20/500) at screening and baseline. The ETDRS score in the non-study eye should be ≥ 60 letters at screening and baseline.
• Sufficiently clear ocular media and adequate pupil dilation to permit fundus photographs of adequate clarity to measure diameters of retinal arteries and veins
• Vital signs as specified in the protocol

Key Exclusion Criteria:

• Concomitant conditions or ocular disorders in the study eye which may, in the opinion of the investigator, confound the interpretation of study results, compromise visual acuity or require medical or surgical intervention during the study period
• High risk and/or/ active proliferative diabetic retinopathy in the study eye, as per investigator assessment at both screening and baseline.
• Participants with the following conditions in the study eye at screening or baseline must be excluded: structural damage of the fovea, vitreous hemorrhage, retinal detachment, vitreomacular traction, macular hole, retinal arterial occlusion, neovascularization of iris of any cause.
• Laser photocoagulation (macular or panretinal) in the study eye during the 6-month period prior to baseline.
• Patients with type 1or type 2 diabetes who have hemoglobin A1C of ≥ 12 at screening
• Other ocular conditions as specified in the protocol
• Systemic conditions as specified in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Cohort 1; open-label, non-randomized, single administration	Drug: MHU650; MHU650 powder for solution for injection
Experimental: Cohort 2; Cohort 2; open-label, non-randomized, single administration	Drug: MHU650; MHU650 powder for solution for injection
Experimental: Cohort 3; Cohort 3, open-label; non-randomized, single administration	Drug: MHU650; MHU650 powder for solution for injection
Experimental: Cohort 4; Cohort 4, open-label, non-randomized, single administration	Drug: MHU650; MHU650 powder for solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ocular and nonocular adverse events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.	Day 1 to Day 60
Change from baseline in Best Correct Visual Acuity (BCVA ) by dose level and timepoint - Study Eye	Best Correct Visual Acuity was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	Day 1 to Day 60
Change from baseline in Central subfield thickness (CSFT) (µm) in the study eye by dose level and timepoint	Central subfield thickness was measured by spectral domain optical coherence tomography (SD-OCT).	Day 1 to Day 60
Change from baseline in Intraocular pressure (IOP) (mmHg) in the study eye by dose level and timepoint	Intraocular pressure was measured per the sites' local standard operating procedures, via tonometry.	Day 1 to Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of single dose of MHU650 - Cmax	Assess serum PK profile of MHU650 by Cmax (if feasibile)	Days 1, 2, 5, 15, 29, 43 and 60
Pharmacokinetics of single dose of MHU650 - Tmax	Assess serum PK profile of MHU650 by Tmax (if feasibile)	Days 1, 2, 5, 15, 29, 43 and 60
Pharmacokinetics of single dose of MHU650 - T1/2	Assess serum PK profile of MHU650 by T1/2 (if feasibile)	Days 1, 2, 5, 15, 29, 43 and 60
Pharmacokinetics of single dose of MHU650 - AUClast	Assess serum PK profile of MHU650 by AUClast (if feasibile)	Days 1, 2, 5, 15, 29, 43 and 60
Pharmacokinetics of single dose of MHU650 - AUCinf	Assess serum PK profile of MHU650 by AUCinf (if feasibile)	Days 1, 2, 5, 15, 29, 43 and 60

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CMHU650A12101 from the Novartis Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): May 24, 2022
• Study Completion (Actual): May 24, 2022

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: macular edema; Diabetic Macular Edema; Macular degeneration; age-related macular degeneration; RVO; Retinal Vein Occlusion; DME; wet macular degeneration; dry macular degeneration; nAMD; Neovascular age-related macular edema; MHU650
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Wet Macular Degeneration
• Other Study ID Numbers: CMHU650A12101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No