A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Patients with Diabetic Macular Edema Treated with Faricimab (RO6867461) - Altimeter Study

Phase 1

Conditions: Diabetic Macular Edema, a complication of Diabetic Retinopathy
MedDRA version: 20.1Level: LLTClassification code 10057934Term: Diabetic macular edemaSystem Organ Class: 100000004853
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2020-001174-30-HR

Lead Sponsor: F.Hoffman-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 80

Inclusion Criteria

Informed Consent
1. Signed ICF prior to any study-related assessments
o All patients are able and willing to provide written informed consent and to comply with the study protocol according to International Council for Harmonisation (ICH) and local regulations.
o Patients are willing to allow AH collection and in the opinion of the Investigator, sampling of >90 µl of AH seems feasible and safe.
2. Ability to comply with the study protocol, in the Investigator’s judgment
Age
3. Age =18 years at the time of signing the ICF
Type of DME Patients and Disease Characteristics
4. Diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association and
o Current regular use of insulin or other injectable drugs (e.g., dulaglutide and liraglutide) for the treatment of diabetes
and/or
o Current regular use of oral anti-hyperglycemic agents for the treatment of diabetes
5. Hemoglobin A1c (HbA1c) =10% (historic values up to 2 months before the screening visit will be permissible; otherwise, the study site may collect a sample for analysis at screening)
6. Patients who are IVT treatment-naïve in the study eye (i.e., have not received previous treatment with any anti-VEGF IVT or any corticosteroids periocular or IVT in the study eye).
Ocular Inclusion Criteria for Study Eye
7. Diabetic macular edema (DME) defined as macular thickening by spectral-domain optical coherence tomography (SD-OCT) involving the center of the macula: CST of =325 µm with Spectralis® (Heidelberg Engineering, Heidelberg, Germany) at screening. This inclusion criterion is to be assessed by the central reading center (CRC).
8. Moderately severe to severe non-proliferative DR (NPDR) (defined as any ETDRS DRSS from 47A through 53E [Ip et al. 2012]) or mild or moderate proliferative DR (PDR) (defined as ETDRS DRSS 60 through 65C [Ip et al. 2012]). This inclusion criterion is to be assessed by the CRC.
9. Decreased VA attributable primarily to DME, with BCVA letter score of 75 to 20 letters (both inclusive) on ETDRS-like charts at the screening visit
10. Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis
Contraception
11. For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined below:
o Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of faricimab.
o A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (=12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the Investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
o Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
o 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

Exclusion Criteria

Medical Conditions
•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
•WOCBP must have a negative serum pregnancy test result within 28 days prior to initiation of faricimab and a negative urine pregnancy test at the baseline visit
•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 AH inflammatory biomarkers. In case of doubt, the Investigator should consult with the Medical Monitor
Prior/Concomitant Therapy
•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, systemic corticosteroids 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
•Mild or moderate NPDR. 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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, AH biomarker patterns, and genetic polymorphisms in patients with DME who are treated with faricimab (RO6867461).;Secondary Objective: Not applicable;Primary end point(s): 1.Change in DRSS between day one and day 112;Timepoint(s) of evaluation of this end point: Up to 29 weeks<br><br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): n/a;Timepoint(s) of evaluation of this end point: N/A

Related Trials