MAGIC: Safety and Efficacy of Faricimab in Patients With NPDR

Sponsor

Greater Houston Retina Research (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05681884

Collaborator

Genentech, Inc. (Industry)

150

Enrollment

Locations

Arms

38.2

Anticipated Duration (Months)

7.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this Phase 2 study is comprised of two groups to evaluate the safety, tolerability, and efficacy of faricimab in patients with Non-Proliferative Diabetic Retinopathy.

Condition or Disease	Intervention/Treatment	Phase
Non-Proliferative Diabetic Retinopathy	Drug: Faricimab	Phase 2

Detailed Description

Group 1: Subjects will be administered intravitreal faricimab every 4 through week 48 and then will be receive faricimab every 16 weeks with an end of study visit at week 96. At any visit after Week 48, if rescue criteria are met, faricimab 6mg will be given every 4 weeks and the subject will continue dosing through the end of the trial.

Group 2: Subjects are seen and observed every 16 weeks. Starting at Week 48, subjects will be administered intravitreal faricimab every 4 weeks from week 48 to week 92 with an end of study visit at week 96. At any visit before Week 48, if rescue criteria are met, faricimab will be given every 4 weeks and the subject will continue dosing through the end of the trial.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized during the enrollment phase of the study in a 1:1 ratio to one of two treatment arms.Randomized during the enrollment phase of the study in a 1:1 ratio to one of two treatment arms.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Faricimab for Retinal Non-Perfusion Associated With Non-Proliferative Diabetic Retinopathy: The MAGIC Phase 2, Multi-Center, Open-Label, Randomized Controlled Trial

Anticipated Study Start Date :

Jan 15, 2023

Anticipated Primary Completion Date :

Feb 15, 2026

Anticipated Study Completion Date :

Mar 23, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Subjects will be administered intravitreal faricimab 6 mg every 4 weeks (defined as every 28 days + 7 days and at least 21 days between injections) through week 48. Starting at Week 48, subjects will be treated every 16 weeks (weeks 48, 64 & 80) with an end of study visit at week 96. Rescue: At any visit after Week 48, if rescue criteria are met, faricimab 6mg will be given every 4 weeks and the subject will continue dosing through the end of the trial.	Drug: Faricimab Faricimab is a humanized bispecific antibody binding to human Ang-2 and VEGF. For Phase III studies, the Ro 686-7461 drug product is provided in single-dose 2-mL glass vials (6 mg/0.05 mL) with L-histidine/acetate buffered solution (approximately pH 5.5) containing sodium chloride, sucrose, L-methionine, polysorbate 20, and water for injection.
Experimental: Group 2 Subjects are seen and observed every 16 weeks. Starting at Week 48, subjects will be administered intravitreal faricimab 6 mg every 4 weeks from week 48 to week 92, (defined as every 28 days ± 7 days and at least 21 days between injections) with an end of study visit at week 96. Rescue: At any visit before Week 48, if rescue criteria are met, faricimab 6mg will be given every 4 weeks and the subject will continue dosing through the end of the trial.	Drug: Faricimab Faricimab is a humanized bispecific antibody binding to human Ang-2 and VEGF. For Phase III studies, the Ro 686-7461 drug product is provided in single-dose 2-mL glass vials (6 mg/0.05 mL) with L-histidine/acetate buffered solution (approximately pH 5.5) containing sodium chloride, sucrose, L-methionine, polysorbate 20, and water for injection.

Arm

Intervention/Treatment

Experimental: Group 1

Subjects will be administered intravitreal faricimab 6 mg every 4 weeks (defined as every 28 days + 7 days and at least 21 days between injections) through week 48. Starting at Week 48, subjects will be treated every 16 weeks (weeks 48, 64 & 80) with an end of study visit at week 96. Rescue: At any visit after Week 48, if rescue criteria are met, faricimab 6mg will be given every 4 weeks and the subject will continue dosing through the end of the trial.

Drug: Faricimab

Faricimab is a humanized bispecific antibody binding to human Ang-2 and VEGF. For Phase III studies, the Ro 686-7461 drug product is provided in single-dose 2-mL glass vials (6 mg/0.05 mL) with L-histidine/acetate buffered solution (approximately pH 5.5) containing sodium chloride, sucrose, L-methionine, polysorbate 20, and water for injection.

Experimental: Group 2

Subjects are seen and observed every 16 weeks. Starting at Week 48, subjects will be administered intravitreal faricimab 6 mg every 4 weeks from week 48 to week 92, (defined as every 28 days ± 7 days and at least 21 days between injections) with an end of study visit at week 96. Rescue: At any visit before Week 48, if rescue criteria are met, faricimab 6mg will be given every 4 weeks and the subject will continue dosing through the end of the trial.

Drug: Faricimab

Outcome Measures

Primary Outcome Measures

Primary Objective [48 weeks]
Analyze the change in the area of retinal non-perfusion (RNP) within the macula over 48 weeks using ultrawide-field fluorescein angiography (UWFA) and optical coherence tomography-angiography (OCT -A) within eyes that have NPDR.
Primary Objective [48 weeks]
Analyze the change in the area of retinal non-perfusion (RNP) outside the macula over 48 weeks using ultrawide-field fluorescein angiography (UWFA) and optical coherence tomography-angiography (OCT -A) within eyes that have NPDR.

Secondary Outcome Measures

Change in area of RNP [Baseline through week 96]
Change in area of RNP, as assessed by a central reading center; linear regression of change in area of RNP (dependent variable) between the monthly faricimab and observation groups, adjusted for age, sex, and disease severity as defined by Baseline ETDRS
Change in area of RNP within the macula [Baseline through week 48 and from baseline through week 96]
Change in area of RNP within the macula, as assessed by ultrawide-field fluorescein; linear regression of change in area of RNP (dependent variable) between the monthly faricimab and observation groups, adjusted for age, sex, and disease severity as defined by Baseline ETDRS
Change in area of RNP outside of the macula [Baseline through week 48 and from baseline through week 96]
Change in area of RNP outside of the macula, as assessed by ultrawide-field fluorescein from baseline to week 96; linear regression of change in area of RNP (dependent variable) between the monthly faricimab and observation groups, adjusted for age, sex, and disease severity as defined by Baseline ETDRS
Percentage of subjects with disease [Baseline through week 96]
Percentage of subjects with neovascularization and/or vitreous hemorrhage and/or DME
Mean change in ETDRS [Baseline through week 48 and from baseline through week 96]
Mean change in ETDRS BCVA
Mean change in CST [Baseline through week 48 and from baseline through week 96]
Mean change in CST

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

- Provide signed IRB-approved informed consent form (ICF) prior to any study-specific procedures
Willing and able to comply with clinic visits and study-related procedures and likely to return for all study visits, in the investigator's judgement
Men or women > 18 years of age at the time of signing the Informed Consent Form
Diagnosis of diabetes mellitus (type 1 or type 2)
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the final dose of study treatment. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a post-menopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of acceptable contraceptive methods include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

Contraception methods that do not result in a failure rate of < 1% per year such as male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide are not acceptable.

The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. If a subject is usually not sexually active but becomes active, they, with their partner, must comply with the contraceptive requirements of the study.

Ocular inclusion criteria for study eye:

Subjects must meet the following ocular inclusion criteria for the study eye for entry into the study:

ETDRS BCVA > 20/400 in the study eye
Non-proliferative diabetic retinopathy, as confirmed by the site investigator
Substantial non-perfusion (defined as greater than 5 disc areas on Wide-Field Fluorescein Angiograph (WFFA)), as assessed by site investigator

Exclusion Criteria:

Any known hypersensitivity to any of the components in the faricimab injection
Any known hypersensitivity to any contrast media (e.g., fluorescein), dilating eye drops, disinfectants (e.g., iodine), or any of the anesthetics and antimicrobial preparations used by the site during the study
Active cancer within the past 12 months prior to Screen/Baseline except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤6 and a stable prostate-specific antigen for >12 months
Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Screen/Baseline
Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab

o Women of childbearing potential must have a negative urine pregnancy test at the Screen/Baseline visit for both Group 1 and Group 2. Women of childbearing potential must also have a negative urine pregnancy test on any visit where they will receive treatment with IP or rescue medication. Urine pregnancy tests must be completed prior to the administration of IP/rescue medication and prior to FA being performed.

Uncontrolled blood pressure, defined as systolic > 190 mmHg and/or diastolic > 110 mmHg (while subject is at rest in a sitting position); if a subject's initial reading exceeds these values, a second reading may be taken ≥30 minutes later the same day
Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Screen/Baseline or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins or minerals) within 3 months (or 5 half-lives, whichever is longer) prior to Screen/Baseline, or during the course of this study
Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives (whichever is longer) prior to Screen/Baseline

Ocular exclusion criteria for study eye:

Subjects who meet any of the following exclusion criteria for the study eye will be excluded from study entry:

Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye prior to Screen/Baseline
SD-OCT central subfield thickness (CST) measurement > 325 µm, in the study eye
Evidence of infectious ocular infection, in the study eye at Screen/Baseline
Any pan-retinal photocoagulation (PRP) treatment received in the study eye prior to Screen/Baseline
Retinal vein occlusion in the study eye
Cystoid macular edema not attributed to diabetes (instead caused by epiretinal membrane, macular telangiectasia, Coats disease, and inherited retinal diseases) in the study eye
Current vitreous hemorrhage obscuring imaging in the study and/or dilated indirect examination
Any intraocular surgery (e.g., cataract surgery) within 4 weeks prior to Screen/Baseline in the study eye
Active intraocular inflammation including scleritis at screening/baseline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Retina Consultants	Bakersfield	California	United States	93309
2	Retinal Consultants Medical Group	Modesto	California	United States	95356
3	Florida Retina Institute	Orlando	Florida	United States	32806
4	Retina Group of Florida	Sarasota	Florida	United States	34233
5	Retina Consultants of Minnesota St. Louis Park	Saint Louis Park	Minnesota	United States	55416
6	Mississippi Retina Associates	Jackson	Mississippi	United States	39202
7	North Carolina Retina Associates	Wake Forest	North Carolina	United States	27587
8	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
9	Palmetto Retina Center	West Columbia	South Carolina	United States	29169
10	Tennessee Retina, PC	Nashville	Tennessee	United States	37203
11	Austin Retina Associates	Austin	Texas	United States	78705
12	Retina Consultants of Texas	Beaumont	Texas	United States	77707
13	Retina Consultants of Texas	Bellaire	Texas	United States	77401
14	Retina Consultants of Texas	Katy	Texas	United States	77494
15	Retina Consultants of Texas	San Antonio	Texas	United States	78240
16	Retina Consultants of Texas	The Woodlands	Texas	United States	77384
17	Retina Associates of Utah	Salt Lake City	Utah	United States	84107
18	Retina Center NW, PLLC	Silverdale	Washington	United States	98383
19	Emanuelli Research and Development Center	Arecibo		Puerto Rico	00612

Sponsors and Collaborators

Greater Houston Retina Research
Genentech, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Greater Houston Retina Research

ClinicalTrials.gov Identifier:

NCT05681884

Other Study ID Numbers:

ML43601

First Posted:

Jan 12, 2023

Last Update Posted:

Jan 26, 2023

Last Verified:

Jan 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Retinal Diseases

Diabetic Retinopathy

Study Results

No Results Posted as of Jan 26, 2023