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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04635800

Collaborator

(none)

Enrollment

Locations

Arms

15.4

Anticipated Duration (Months)

1.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label study is being conducted to evaluate the initial safety and tolerability of IVT MHU650 in patients with DME, AMD, or RVO. The primary objective of this study is to evaluate the safety and tolerability of single ascending doses of IVT MHU650 in patients with macular edema. The secondary objective of this study is to evaluate the serum pharmacokinetic profile of total MHU650 following single IVT dose of MHU650 in macular edema patients.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema Diabetic Macular Edema Neovascular Age-related Macular Degeneration Retinal Vein Occlusion	Drug: MHU650	Phase 1

Detailed Description

This is an open-label, multi-center, FIH study which employs a single ascending dose (SAD) design to assess the safety, tolerability and pharmacokinetics (PK) of single IVT doses of MHU650 in up to 24 patients with macular edema. 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) during which ophthalmic, medical and safety laboratories will be performed. A post study safety phone contact call will occur 30 days after the EOS visit. Patients can receive rescue treatment at any time during the study following MHU650 administration.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Masking Description:

Open-label; no masking

Primary Purpose:

Treatment

Official Title:

A First-in-human, Open-label, Single Ascending Dose Study to Assess Safety and Tolerability of Intravitreal MHU650 in Patients With Macular Edema

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Mar 24, 2022

Anticipated Study Completion Date :

Mar 25, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of participants with ocular and nonocular adverse events [Day 1 through Day 60]
To evaluate the safety and tolerability of a single IVT dose of MHU650 over 2 months post dose by reviewing ophthalmic, medical examination and safety laboratories. To characterize ocular and non-ocular safety by the incidence of treatment-emergent adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (AMD), or retinal vein occlusion (RVO), in the opinion of the investigator:
Early Treatment Diabetic Retinopathy (ETDRS) letter score in the study eye must be worse than 60 letters (20/63) but better than 24 letters (20/320) 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:

Proliferative diabetic retinopathy in the study eye

The following is permitted as an exception:

Tufts of neovascularization less than one disc area with no vitreous hemorrhage
Focal, peripheral retinal areas treated with photocoagulation with fewer than 30 laser burns performed at least 6 months preceding Day 1
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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Huntington Beach	California	United States	92647
2	Novartis Investigative Site	Irvine	California	United States	92697
3	Novartis Investigative Site	Rancho Cordova	California	United States	95670
4	Novartis Investigative Site	Altamonte Springs	Florida	United States	32701
5	Novartis Investigative Site	Deerfield Beach	Florida	United States	33064
6	Novartis Investigative Site	Honolulu	Hawaii	United States	96813
7	Novartis Investigative Site	Hagerstown	Maryland	United States	21740
8	Novartis Investigative Site	Austin	Texas	United States	78793
9	Novartis Investigative Site	Houston	Texas	United States	77030
10	Novartis Investigative Site	Arecibo		Puerto Rico	00612