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

Diabetic Macular Edema Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04635800
• Other study ID #: CMHU650A12101
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2020
• Est. completion date: May 24, 2022

Study information

• Verified date: May 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 24, 2022
• Est. primary completion date: May 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Degeneration
• Macular Edema
• Neovascular Age-related Macular Degeneration
• Retinal Vein Occlusion
• Wet Macular Degeneration

Intervention

Drug:
• MHU650
MHU650 powder for solution for injection

Locations

Country	Name	City	State
Puerto Rico	Novartis Investigative Site	Arecibo
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Hagerstown	Maryland
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Huntington Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Results for CMHU650A12101 from the Novartis Trials Website