A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Participants With Diabetic Macular Edema Treated With Faricimab

Diabetic Macular Edema Clinical Trial

— ALTIMETER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04597918
• Other study ID #: MR41926
• Secondary ID: 2020-001174-30
• Status: Completed
• Phase: Phase 2
• Start date: November 25, 2020
• Est. completion date: December 22, 2022

Study information

• Verified date: November 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: December 22, 2022
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• Faricimab
A 6-milligram (mg) dose of faricimab will be administered intravitreally (IVT) in the study eye once every 4 weeks (Q4W).

Locations

Country	Name	City	State
Argentina	Centro Oftalmológico Dr. Charles S.A.	Capital Federal
Argentina	Oftalmos	Capital Federal
Canada	Vitreous Retina Macula Specialists of Toronto	Etobicoke	Ontario
Canada	The Retina Centre of Ottawa	Ottawa	Ontario
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	Irccs Ospedale San Raffaele;U.O. Oculistica	Milano	Lombardia
Italy	Ospedale San Giuseppe; U.O. Oculistica	Milano	Lombardia
Poland	Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy	Warszawa
United Kingdom	Gloucestershire Hospitals NHS Foundation Trust	Gloucestershire
United Kingdom	Kings College Hospital	London
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Retina Res Institute of Texas	Abilene	Texas
United States	Austin Research Center for Retina	Austin	Texas
United States	Northwestern Medical Group/Northwestern University	Chicago	Illinois
United States	Charles Retina Institute	Germantown	Tennessee
United States	Cumberland Valley Retina PC	Hagerstown	Maryland
United States	Long Is. Vitreoretinal Consult	Hauppauge	New York
United States	Raj K. Maturi, MD PC	Indianapolis	Indiana
United States	Bascom Palmer Eye Institute	Naples	Florida
United States	University Retina and Macula Associates, PC	Oak Forest	Illinois
United States	The Retina Institute	Saint Louis	Missouri
United States	Retina Consultants of Texas	The Woodlands	Texas
United States	Strategic Clinical Research Group, LLC	Willow Park	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Germany,  Italy,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The ETDRS DRSS score of each participant's study eye was assessed using ultra-wide field color fundus photography (UWF-CFP) taken by trained personnel at the study sites. Analysis of the fundus photographs was performed by the central reading center, and the percentage of participants with a =2-step improvement from baseline was summarized along with a two-sided 95% Clopper-Pearson exact confidence interval. Baseline was defined as the participant's last observation prior to initiation of study drug.	Baseline and Week 24
Secondary	Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for visit, age (continuous), baseline BCVA (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.	From Baseline to Week 24
Secondary	Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using Spectral Domain-Optical Coherence Tomography (SD-OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model was adjusted for visit, age (continuous), baseline CST (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.	From Baseline to Week 24
Secondary	Median Time to First Absence of DME in the Study Eye During the Study	An event was defined as the first absence of diabetic macular edema (DME) in the study eye, defined as first time reaching central subfield thickness (CST; ILM-RPE) <305 microns, after baseline. Baseline was defined as the participant's last observation prior to initiation of study drug. The time to first absence of DME was a Kaplan-Meier estimate. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. Participants without an event and discontinued from treatment were censored at the last CST assessment.	From Baseline to Week 24
Secondary	Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24	The absence of intraretinal fluid (IRF) in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of IRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported.	Week 24
Secondary	Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24	The absence of subretinal fluid (SRF) in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of SRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported.	Week 24