Clinical trial NCT04635800: A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of IVT MHU650 in Macular Edema Patients
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Macular Edema
Diabetic Macular Edema
Neovascular Age-related Macular Degeneration
Retinal Vein Occlusion
Keywords: Macular degeneration
age-related macular degeneration
dry macular degeneration
wet macular degeneration
Diabetic Macular Edema
DME
Neovascular age-related macular edema
nAMD
Retinal Vein Occlusion
RVO
MHU650
macular edema
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-11-19
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The primary objective of this open-label study is to evaluate the initial safety, tolerability, and pharmacokinetics (PK) of single IVT doses of MHU650 in up to 24 patients. The screening period will be up to 60 days. A single dose of MHU650 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. A total of up to 4 cohorts may be enrolled, with an additional optional lower or intermediate cohort of 6 participants.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with ocular and nonocular adverse events
timeFrame: Day 1 to Day 60
measure: Change from baseline in Best Correct Visual Acuity (BCVA ) by dose level and timepoint - Study Eye
timeFrame: Day 1 to Day 60
measure: Change from baseline in Central subfield thickness (CSFT) (µm) in the study eye by dose level and timepoint
timeFrame: Day 1 to Day 60
measure: Change from baseline in Intraocular pressure (IOP) (mmHg) in the study eye by dose level and timepoint
timeFrame: Day 1 to Day 60
Secondary outcomes:
measure: Pharmacokinetics of single dose of MHU650 - Cmax
timeFrame: Days 1, 2, 5, 15, 29, 43 and 60
measure: Pharmacokinetics of single dose of MHU650 - Tmax
timeFrame: Days 1, 2, 5, 15, 29, 43 and 60
measure: Pharmacokinetics of single dose of MHU650 - T1/2
timeFrame: Days 1, 2, 5, 15, 29, 43 and 60
measure: Pharmacokinetics of single dose of MHU650 - AUClast
timeFrame: Days 1, 2, 5, 15, 29, 43 and 60
measure: Pharmacokinetics of single dose of MHU650 - AUCinf
timeFrame: Days 1, 2, 5, 15, 29, 43 and 60
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Honolulu
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Hagerstown
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Arecibo
country: Puerto Rico
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: