NLP SNP

This study will evaluate the long-term safety and tolerability of RO7234292 (RG6042) in participants who have completed other F. Hoffmann-La Roche, Ltd.-sponsored and/or Genentech-sponsored studies in the Huntington's disease (HD) in the development program for RG6042.

NCT03842969 Huntington Disease Drug: RO7234292 (RG6042)

MeSH: Huntington Disease

Upon completion of the inclusion visit, eligible patients will receive either RO7234292 (RG6042) every 8 weeks (Q8W) or RO7234292 (RG6042) every 16 weeks (Q16W) by bolus intrathecal injection. --- Q16W ---

Primary Outcomes

Measure: Percentage of Participants with Adverse Events

Time: Up to approximately 5 years

Description: The Columbia-Suicide Severity Rating Scale (C-SSRS) is a structured tool to assess suicidal ideation and behavior. Four constructs are measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories, and composite endpoints based on the categories are followed over time to monitor patient safety.

Measure: Change From Baseline in Behavioral Findings, as Assessed by the Columbia-Suicide

Time: Baseline, Every 8 Weeks or Every 16 Weeks, and End of Treatment (up to approximately 5 years)

Description: MoCA contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0−30, where lower scores indicate greater impairment.

Measure: Change From Baseline in Cognition, using Montreal Cognitive Assessment (MoCA)

Time: Baseline, Every 16 Weeks, End of Treatment (up to approximately 5 years)

2 A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of RO6867461 in Patients With Diabetic Macular Edema (RHINE)

This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

NCT03622593 Diabetic Macular Edema Drug: Aflibercept Drug: Faricimab Drug: Sham Procedure

MeSH: Edema Macular Edema

HPO: Anasarca Cystoid macular edema Edema Macular edema

Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 1 Year. --- Q12W --- --- Q16W ---

Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 2 Years. --- Q12W --- --- Q16W ---

Primary Outcomes

Description: As measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters.

Measure: Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) at 1 Year

Time: Baseline (Day 1) and 1 year

Secondary Outcomes

Measure: Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at 1 Year

Time: Baseline and 1 year

Measure: Change From Baseline in BCVA Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥0 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With a ≥2-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With a ≥3-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥15 Letters or Achieving BCVA of ≥84 Letters Over Time

Time: Up to 2 years

Measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time

Time: Up to 2 years

Measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time

Time: Up to 2 years

Measure: Percentage of Participants Who Develop New Proliferative Diabetic Retinopathy Over Time

Time: Up to 2 years

Measure: Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 1 Year

Time: 1 year

Measure: Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 2 Years

Time: 2 years

Measure: Change From Baseline in Central Subfield Thickness (CST) Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants with Absence of DME Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Intraretinal Fluid Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Subretinal Fluid Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid Over Time

Time: Up to 2 years

Measure: Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With Ocular Adverse Events

Time: Up to 2 years

Measure: Percentage of Participants With Non-Ocular Adverse Events

Time: Up to 2 years

Measure: Plasma Concentration of Faricimab Over Time

Time: Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

Measure: Percentage of Participants With Presence of Anti-Drug Antibodies

Time: Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

3 A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of RO6867461 in Patients With Diabetic Macular Edema (YOSEMITE)

NCT03622580 Diabetic Macular Edema Drug: Aflibercept Drug: Faricimab Drug: Sham Procedure

MeSH: Edema Macular Edema

HPO: Anasarca Cystoid macular edema Edema Macular edema

Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 1 Year. --- Q12W --- --- Q16W ---

Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 2 Years. --- Q12W --- --- Q16W ---

Primary Outcomes

Description: As measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters.

Measure: Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) at 1 Year

Time: Baseline (Day 1) and 1 year

Secondary Outcomes

Measure: Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at 1 Year

Time: Baseline and 1 year

Measure: Change From Baseline in BCVA Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Avoiding a Loss of ≥0 Letters in BCVA From Baseline Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With a ≥2-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With a ≥3-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants Gaining ≥15 Letters or Achieving BCVA of ≥84 Letters Over Time

Time: Up to 2 years

Measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time

Time: Up to 2 years

Measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time

Time: Up to 2 years

Measure: Percentage of Participants Who Develop New Proliferative Diabetic Retinopathy Over Time

Time: Up to 2 years

Measure: Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 1 Year

Time: 1 year

Measure: Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 2 Years

Time: 2 years

Measure: Change From Baseline in Central Subfield Thickness (CST) Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants with Absence of DME Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Intraretinal Fluid Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Subretinal Fluid Over Time

Time: Up to 2 years

Measure: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid Over Time

Time: Up to 2 years

Measure: Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time

Time: From Baseline up to 2 years

Measure: Percentage of Participants With Ocular Adverse Events

Time: Up to 2 years

Measure: Percentage of Participants With Non-Ocular Adverse Events

Time: Up to 2 years

Measure: Plasma Concentration of Faricimab Over Time

Time: Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

Measure: Percentage of Participants With Presence of Anti-Drug Antibodies

Time: Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

HPO Nodes

Cystoid macular edema

Genes 14

MFRP HLA-A RLBP1 PRPF8 RDH5 POMGNT1 REEP6 PRPH2 DHDDS ARHGEF18 ARL3 RHO PDE6G NOD2

Anasarca

Genes 3

UBR1 PLVAP PMM2