Diabetic Macular Edema
Conditions
Brief summary
This study will assess the safety and tolerability of RO7497372 in participants with DME. The study consists of 2 parts. Part 1 will test multiple-ascending doses of RO7497372 after unilateral intravitreal (IVT) administration in participants with DME. The main purpose of Part 1 is to provide data for RO7497372 safety and tolerability, as well as to characterize the ocular and systemic pharmacokinetics (PK), systemic anti-drug antibodies (ADA), and duration of target engagement, i.e., the pharmacodynamics (PD) in aqueous humor (AH) and blood. Part 2 will evaluate the safety, tolerability, PK, and PD of two dose strengths of RO7497372 (low dose and high dose), identified as safe and tolerated in Part 1.
Interventions
DRUGRO7497372
RO7497372 will be administered as IVT injection as per the schedule specified in the arms.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 is Sequential Assignment. Part 2 is Parallel Assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of diabetes mellitus (type 1 or type 2), as defined by the world health organization (WHO) and/or American Diabetes Association * Participant consents to AH collection * Collection of \> 90 microlitres (µL) AH (at each visit required per schedule of activities \[SoA\]) if deemed feasible and safe by the Investigator. * Macular thickening secondary to DME involving the center of the fovea with CST \>= 325 µm at screening * Decreased BCVA primarily due to DME with ETDRS score of 78 to 19 letters (both inclusive) at screening * Adequately clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images * Diagnosis of non-proliferative DR * Treatment-naive and Pre-treated participants after washout
Exclusion criteria
* Any major illness or major surgical procedure ≤ 4 weeks before Day 1 * Any febrile illness and associated sequelae ≤ 1 week prior to Day 1 * Active cancer ≤ 1 year prior to Day 1 * Cerebral vascular accident (including stroke and transient ischemic attack) or myocardial infarction ≤ 24 weeks prior to Day 1 * HbA1c ≥ 12% at screening * Any panretinal photocoagulation or macular laser photocoagulation treatment prior to Day 1 * History of vitreoretinal surgery/pars plana vitrectomy * Any cataract surgery within 12 weeks prior to Day 1 or any planned surgery during the study * History of any glaucoma surgery including laser glaucoma procedures * Uncontrolled glaucoma * Any active intra- or periocular infection on Day 1 * Any active or history of Intraocular inflammation * Intravitreal treatment with an anti-IL-6 (e.g., vamikibart) or anti-IL-6 receptor treatment at any time * Any proliferative DR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AEs) | Up to 28 Weeks | — |
| Part 2: Number of Participants With Intraocular Inflammation (IOI) AEs as Reported by the Investigator | Baseline to Week 48 | — |
| Part 2: Number of Participants With Severe or Serious Drug-Related IOI AEs | Baseline to Week 48 | Number of participants with severe or serious drug-related IOI AEs severity will be determined according to the DAIDS toxicity grading scale as reported by the Investigator. |
| Part 2: Number of Participants With Occlusive Retinal Vasculitis AEs as Reported by the Investigator | Baseline to Week 48 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Concentration of RO7497372 in Blood | Up to Week 28 | — |
| Part 1: Concentration of RO7497372 in Aqueous Humor (AH) | Up to Week 28 | — |
| Part 2: Number of Participants With AEs | Up to 56 weeks | Number of participants with AEs severity determined according to the DAIDS toxicity grading scale. |
| Part 2: Number of Participants With Persistent Treatment-induced Anti-drug Antibody (ADAs) | Up to 56 weeks | — |
| Part 2: Concentration of RO7497372 in AH | Up to Week 56 | — |
| Part 2: Concentration of RO7497372 in Plasma | Up to Week 56 | — |
| Part 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) Score Over Time | From Baseline (Day 1) up to Week 56 | BCVA will be measured via Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters using a set of three Precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity (VA) examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicates improvement in VA. |
| Part 2: Absolute Value of BCVA Score Over Time | Up to Week 56 | BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicates improvement in VA. |
| Part 2: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time | Up to Week 56 | BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicates improvement in VA. |
| Part 2: Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time | Up to Week 56 | BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicates improvement in VA. |
| Part 2: Change From Baseline in Central Subfield Thickness (CST) Over Time | From Baseline (Day 1) up to Week 56 | CST is defined as the average thickness of the central 1-mm circle of the ETDRS grid centered to the fovea measured between the internal limiting membrane and the Bruch's membrane. CST will be determined by CRC evaluation of SD-OCT images. |
| Part 2: Absolute Value of CST Over Time | Up to Week 56 | CST is defined as the average thickness of the central 1-mm circle of the ETDRS grid centered to the fovea measured between the internal limiting membrane and the Bruch's membrane. CST will be determined by CRC evaluation of SD-OCT images. |
| Part 2: Percentage of Participants With Absence of DME Over Time | Up to Week 56 | Absence of DME is defined as CST \< 325 micrometre (μm) by spectral domain optical coherence tomography (SD-OCT). |
| Part 2: Percentage of Participants With Absence of Intraretinal Fluid and/or Subretinal Fluid Over Time | Up to Week 56 | Presence of intraretinal and subretinal fluid will be determined by CRC evaluation of SD -OCT images. |
| Part 2: Percentage of Participants With ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) Improvement From Baseline on the ETDRS DRSS Over Time | Up to Week 56 | The DRSS will be graded according to ETDRS grading schedules from report 18 JOVS, February 1998, Vol. 39, No. 2. ETDRS DRSS is 13 step scale which measures severity of diabetic retinopathy (DR). The DRSS scores vary from 10 (DR absent) to 90 (ungradable proliferative diabetic retinopathy(PDR)). Higher levels indicate higher severity. |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed