Clinical trial NCT04597918: A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Participants With Diabetic Macular Edema Treated With Faricimab
Official title: An Exploratory, Prospective, Multi-Center, Open-Label, Single-Arm, Interventional, Phase IIB Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Patients With Diabetic Macular Edema Treated With Faricimab (RO6867461) - ALTIMETER STUDY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an exploratory, prospective, multicenter, open-label, single-arm, interventional, Phase IIb study designed to explore the associations over time between clinical assessments, multimodal imaging assessments, aqueous humor (AH) biomarker patterns, and genetic polymorphisms in participants with diabetic macular edema (DME) who are treated with faricimab.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association
* Hemoglobin A1c (HbA1c) ≤10%
* Patients who are intravitreal (IVT) treatment-naïve in the study eye
* Diabetic macular edema (DME) defined as macular thickening by spectral-domain optical coherence tomography (SD-OCT) involving the center of the macula. This inclusion criterion is to be assessed by the central reading center (CRC).
* Decreased visual acuity (VA) attributable primarily to DME
* Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis

Exclusion Criteria:

* Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1
* Any known hypersensitivity to any of the components in the faricimab injection, dilating eye drops, or any of the anesthetics and antimicrobial preparations used by the patient during the study
* Any major illness or major surgical procedure within 1 month before the Day 1. One re-screening for this criterion is permitted
* History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the Investigator
* Active cancer within the past 12 months prior to Day 1 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 or myocardial infarction within 12 months prior to the Day 1. One re-screening for this criterion is permitted
* Any febrile illness within 1 week prior to Day 1. One re-screening for this criterion is permitted
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab
* Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
* Any condition resulting in a compromised immune system that is likely to impact the aqueous humor (AH) inflammatory biomarkers.
* Patients who are currently enrolled in or have participated in any other clinical study involving an investigational product or device, or in any other type of medical research, within 3 months or 5 half-lives prior to Day 1 and up to completion of the current study
* Substance abuse occurring within 12 months prior to screening, in the Investigator's judgment
* Use of systemic immunomodulatory treatments within 6 months or 5 half-lives prior to Day 1
* Use of any systemic corticosteroids (including inhaled corticosteroids from inhalers used regularly, e.g., pulmonary disease, asthma, or seasonal allergy) within 1 month prior to Day 1
* Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives prior to Day 1
* Use of systemic medications known to be toxic to the lens, retina or optic nerve used during the 6-month period or 5 half-lives prior to Day 1 or likely need to be used
* Received a blood transfusion within 3 months prior to the screening visit
* Received any treatment that leads to immunosuppression within 6 months or 5 half-lives prior to Day 1

Ocular Exclusion Criteria for Study Eye:

* High-risk PDR. This exclusion criterion is to be assessed by the CRC
* Any history of or ongoing rubeosis iridis
* Any panretinal photocoagulation or macular laser photocoagulation treatment received in the study eye prior to the screening visit or expected to be received between the screening visit and Day 1
* Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye and no such treatment planned for the time between screening and Day 1
* Any treatment for dry eye disease in the last month prior to Day 1. Lubricating eye drops and ointments are permitted.
* Any treatment with anti-inflammatory eye drops within 1 month prior to Day 1
* Any intraocular surgery within 3 months prior to Day 1 or any planned surgery during the study
* Any glaucoma surgery/laser procedure involving the iris, trabecular meshwork, or ciliary body prior to the screening visit. Only iris surgery/laser might be allowed if they occurred more than 6 months prior to Day 1.
* History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy
* Any active or suspected ocular or periocular infections on Day 1
* Any presence of active intraocular inflammation on Day 1 or any history of intraocular inflammation
* Any history of idiopathic, infectious, or noninfectious uveitis
* Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision
* Any current ocular condition or other causes of visual impairment for which, in the opinion of the Investigator, VA loss would not improve from resolution of macular edema

Ocular Exclusion Criteria for Fellow Eye:

* Patient is currently receiving treatment with brolucizumab or bevacizumab in the non-study eye and is unwilling to switch to a protocol allowed non-study eye treatment during the study
* Any previous treatment with Iluvien® or Retisert® in the non-study eye
* Non-functioning non-study eye

Primary outcomes:
measure: Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24
timeFrame: From Baseline to Week 24
measure: Median Time to First Absence of DME in the Study Eye During the Study
timeFrame: From Baseline to Week 24
measure: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Naples
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Group/Northwestern University
state: Illinois
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Indianapolis
country: United States
facility: Raj K. Maturi, MD PC
state: Indiana
city: Hagerstown
country: United States
facility: Cumberland Valley Retina PC
state: Maryland
city: Saint Louis
country: United States
facility: The Retina Institute
state: Missouri
city: Hauppauge
country: United States
facility: Long Is. Vitreoretinal Consult
state: New York
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Abilene
country: United States
facility: Retina Res Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Research Center for Retina
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Capital Federal
country: Argentina
facility: Centro Oftalmológico Dr. Charles S.A.
city: Capital Federal
country: Argentina
facility: Oftalmos
city: Etobicoke
country: Canada
facility: Vitreous Retina Macula Specialists of Toronto
state: Ontario
city: Ottawa
country: Canada
facility: The Retina Centre of Ottawa
state: Ontario
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Milano
country: Italy
facility: Ospedale San Giuseppe; U.O. Oculistica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;U.O. Oculistica
state: Lombardia
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy
city: Gloucestershire
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: