Multiple Dose Safety and Efficacy of LKA651 in Patients W... | NCT03927690

NCT03927690

ID	Type	Description	Link
2018-000031-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LKA651	Experimental	LKA651 Intravitreal injection	Drug: LKA651
LKA651 + Lucentis	Experimental	LKA651 + Lucentis Intravitreal injection	Drug: LKA651 Drug: Lucentis
Lucentis	Active Comparator	Lucentis Intravitreal injection	Drug: Lucentis

Name	Type	Description	Arm Group Labels	Other Names
LKA651	Drug	LKA651 5 mg Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase	LKA651 LKA651 + Lucentis

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events	An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient. The severity of the AEs (mild, moderate, severe) was based on the Common Terminology Criteria for Adverse Events (CTCAE). Number of participants in each category is reported in the table. A participant who falls multiple times in one category is counted only once.	Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye	An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient.	Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
Number of Participants With Non-ocular Adverse Events (>=2%)	An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient.	Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
Intraocular Pressure (IOP) in Study Eye	Intraocular pressure was measured per the study site's regular practice.	Screening, and Day 85
Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12		Week 12 (Day 85) up to Day 140
Time to Retreatment in Study Eye With Anti-VEGF After Week 12	Time to retreatment with anti VEGF (as determined by the investigator) after Week 12 during the additional 12 week extension phase (that was up to 16 weeks after the last dose) was examined with a Kaplan Meier plot.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Written informed consent must be obtained before any assessment is performed.
Male and female patients age 18 to 85 years of age inclusive at screening
Presence of type I or type II diabetes mellitus
The Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye must be between 24 and 70 letters (approximate Snellen equivalent of 20/40-20/320). The non-study eye (fellow eye) should be ≥34 letters or better (approximate Snellen equivalent of 20/200) at screening
Presence of Diabetic macular edema (DME) in the study eye, with decrease in vision due to foveal thickening of central macular thickness ≥ 320 µm in the central subfield, as assessed on Spectral domain optical coherence tomography (SD-OCT) and confirmed by the central reading center at screening
Sufficiently clear ocular media and adequate pupil dilation in the study eye to permit fundus photographs of adequate clarity to measure diameters of retinal arteries and veins at screening

Exclusion criteria

Patient with history of intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) treatment in the study eye <90 days from baseline
Patient with history of intraocular corticosteroids including dexamethasone intravitreal implants during the 6 month period prior to baseline. Any prior use of fluocinolone acetonide intravitreal implant (Iluvien) is prohibited regardless of timing
Laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline.
High risk proliferative diabetic retinopathy
Patients, with type 1 or type 2 diabetes who have a hemoglobin A1C ≥ 12% at screening.
Any progressive disease of the retina in the study eye (e.g. uveitis,rod-cone dystrophy) or optic nerve
Area of macular retinal ischemia (as measured by the foveal avascular zone) ≥ 1000 μm.
Active intraocular inflammation (graded as trace or above) or active intraocular infection in either eye.
Current diagnosis of or laboratory evidence for anemia, defined as a hemoglobin <10 g/dL for women and <11 g/dL for men.

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Beverly Hills	California	90211	United States
Novartis Investigative Site

References Module

Label	URL
Patient Lay Trial Summary	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
FG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 6, 2022	Aug 4, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
BG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
BG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00061.6± 8.58 BG00163.8± 8.18 BG00261.2± 9.02 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0009 BG00113 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Events

An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient.

The severity of the AEs (mild, moderate, severe) was based on the Common Terminology Criteria for Adverse Events (CTCAE).

Number of participants in each category is reported in the table. A participant who falls multiple times in one category is counted only once.

Safety Set

Posted

Count of Participants

Participants

Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants	OG00028 OG00130 OG00233

Title

Denominators

Categories

AEs, Patients with AEs

Title	Measurements
	OG00020 OG00116 OG00219

AEs of mild intensity

Primary

Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye

An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient.

Safety Set

Posted

Count of Participants

Participants

Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Primary

Number of Participants With Non-ocular Adverse Events (>=2%)

An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient.

Safety Set

Posted

Count of Participants

Participants

Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Primary

Intraocular Pressure (IOP) in Study Eye

Intraocular pressure was measured per the study site's regular practice.

Safety analysis set

Posted

Mean

Standard Deviation

mmHg

Screening, and Day 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Primary

Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye

BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.

Visual function of the study eye was assessed using the ETDRS protocol.

BCVA in study eye was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Baseline BCVA value and treatment naïve and treatment experienced variable were used as covariates.

Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.

Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.

Posted

Mean

90% Confidence Interval

Scores on a scale

Days 2, 8, 15, 29, 43, 57, and 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis

Primary

Inner Macular Thickness (Inferior)

Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.

Posted

Mean

Standard Deviation

micrometer

Week 12 (Day 85)

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Primary

Inner Macular Thickness (Temporal)

Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.

Posted

Mean

Standard Deviation

micrometer

Week 12 (Day 85)

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Primary

Outer Macular Thickness (Inferior)

Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.

Posted

Mean

Standard Deviation

micrometer

Week 12 (Day 85)

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Primary

Outer Macular Thickness (Temporal)

Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.

Posted

Mean

Standard Deviation

micrometer

Week 12 (Day 85)

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Primary

Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye

Foveal avascular zone was assessed by fluorescein angiography (FA).

Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.

Posted

Count of Participants

Participants

Days 29, 57, 85, End of Study (Up to Day 140)

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts

Primary

Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye

Central subfield thickness was measured by spectral domain optical coherence tomography (SD-OCT). Central subfield retinal thickness was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Log-transformed baseline central subfield retinal thickness and treatment naïve and treatment experienced variable were used as covariates. Results were back-transformed to show results as a ratio to baseline.

Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.

Posted

Geometric Mean

90% Confidence Interval

ratio

Days 8, 15, 29, 43, 57, 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis

Secondary

Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12

Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.

Posted

Count of Participants

Participants

Week 12 (Day 85) up to Day 140

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Secondary

Time to Retreatment in Study Eye With Anti-VEGF After Week 12

Time to retreatment with anti VEGF (as determined by the investigator) after Week 12 during the additional 12 week extension phase (that was up to 16 weeks after the last dose) was examined with a Kaplan Meier plot.

Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.

Posted

Median

95% Confidence Interval

Days after Day 85 (Week 12)

Week 12 (Day 85) up to Day 140

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Secondary

Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651

PK parameters were determined using non-compartmental methods using the most recent version of WinNonlin Phoenix (Version 8.2).

Concentrations below the lower limit of quantification (LLOQ) were treated as 1/2 LLOQ in summary statistics.

Pharmacokinetic analysis set. Concentrations below the Lower Limit of Quantification (LLOQ) are reported as zero.

Posted

Mean

Standard Deviation

ng/mL

Day 1 (0, 0.5 and 4 hrs post dose), Day 2, Day 8, Day 15, Day 29 (0, 0.5 and 4 hrs post dose), Day 43, Day 57 (0, 0.5 and 4 hrs post dose), Day 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Secondary

Summary Statistics of Pharmacokinetics - AUC0-28d of LKA651 (Serum)

Area under the curve over the dosing interval 0 to 28 days.

Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of LKA651 concentrations above the lower limit of quantification.

Posted

Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts

Secondary

Summary Statistics of Pharmacokinetics - Serum Concentrations of Lucentis

Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of Lucentis concentrations above the lower limit of quantification.

Posted

Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts
Participants

Secondary

Summary Statistics of Pharmacokinetics - AUC0-28d of Lucentis (Serum)

Area under the curve over the dosing interval 0 to 28 days.

Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of Lucentis concentrations above the lower limit of quantification.

Posted

Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Units	Counts

Post-Hoc

All Collected Deaths

On-treatment deaths are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).

Post-treatment deaths are reported for the timeframe of greater than 30 days after last treatment, until study completion, up to approximately 168 days.

All deaths refer to the sum of on-treatment and post-treatment deaths.

Safety Set

Posted

Count of Participants

Participants

On-treatment - up to 12 weeks; Post-treatment - greater than 30 days after last treatment, until study completion, up to approximately 168 days

ID	Title	Description
OG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase
OG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LKA651	LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase	1	28	3	28	20	28
EG001	LKA651 + Lucentis	LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase	0	30	4	30	16	30
EG002	Lucentis	Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase	0	33	1	33	19	33
EG003	Total	Total	1	91	8	91	55	91

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina unstable	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG0031 affected91 at risk
Retinal detachment	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Cyclic vomiting syndrome	Gastrointestinal disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
COVID-19	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Pneumonia	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Bone cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0012 affected30 at risk EG0021 affected33 at risk EG0034 affected91 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Atrioventricular block first degree	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Abnormal sensation in eye	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Anterior chamber flare	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0015 affected30 at risk EG0022 affected33 at risk EG003
Corneal erosion	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Cystoid macular oedema	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Dacryostenosis acquired	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Diabetic retinal oedema	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0003 affected28 at risk EG0011 affected30 at risk EG0022 affected33 at risk EG003
Diabetic retinopathy	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0021 affected33 at risk EG003
Dry eye	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0021 affected33 at risk EG003
Epiretinal membrane	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Eye pain	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Eyelids pruritus	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Lenticular opacities	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Macular oedema	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0002 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Ocular hypertension	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0002 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Punctate keratitis	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Retinal cyst	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Retinal exudates	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Retinal oedema	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0003 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Vitreoretinal traction syndrome	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Vitreous haemorrhage	Eye disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0022 affected33 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Adenoviral conjunctivitis	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0021 affected33 at risk EG003
COVID-19	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0002 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Coronavirus infection	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0012 affected30 at risk EG0020 affected33 at risk EG003
Sinusitis	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0012 affected30 at risk EG0020 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0021 affected33 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
XIIth nerve injury	Injury, poisoning and procedural complications	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Blood cholesterol increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Blood creatinine increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0002 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Blood glucose increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Blood triglycerides increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Blood urea increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Glycosylated haemoglobin increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Intraocular pressure increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Lipase increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Pancreatic enzymes increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Prostatic specific antigen increased	Investigations	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Urine ketone body present	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Urine leukocyte esterase positive	Investigations	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0022 affected33 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0002 affected28 at risk EG0011 affected30 at risk EG0021 affected33 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0012 affected30 at risk EG0021 affected33 at risk EG003
Vitamin B complex deficiency	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Sjogren's syndrome	Musculoskeletal and connective tissue disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Headache	Nervous system disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
VIth nerve paralysis	Nervous system disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected30 at risk EG0020 affected33 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (25.0)	Systematic Assessment	EG0001 affected28 at risk EG0010 affected30 at risk EG0020 affected33 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Essential hypertension	Vascular disorders	MedDRA (25.0)	Systematic Assessment	EG0000 affected28 at risk EG0010 affected30 at risk EG0021 affected33 at risk EG003
Hypertension	Vascular disorders	MedDRA (25.0)	Systematic Assessment	EG0003 affected28 at risk EG0011 affected30 at risk EG0023 affected33 at risk EG003

First MCP Posted Date

ID	Term
D008268	Macular Degeneration
D014786	Vision Disorders
D057092	Geographic Atrophy
D057135	Wet Macular Degeneration
D012170	Retinal Vein Occlusion
D008269	Macular Edema
D003930	Diabetic Retinopathy

Ancestor Terms

ID	Term
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases
D012678	Sensation Disorders
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D020246	Venous Thrombosis
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D003925	Diabetic Angiopathies
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases

ID	Term
D000069579	Ranibizumab

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

OG00024
OG00128
OG00231

OG00024
OG00128
OG00231

OG00023
OG00128
OG00231

OG00023
OG00128
OG00231

Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase

OG00025
OG00129
OG00232

Units	Counts
Participants	OG00023 OG00128 OG0020

OG0000
OG0010
OG0020

Units	Counts
Participants	OG00028 OG00130 OG00233

OG00168.6(66.1 to 71.2)

OG00266.2(63.4 to 69.0)

OG00168.6(65.8 to 71.4)

OG00268.4(65.4 to 71.3)

OG00168.2(65.3 to 71.0)

OG00268.5(65.9 to 71.1)

OG00170.4(67.6 to 73.3)

OG00269.1(66.2 to 71.9)

OG00171.5(68.6 to 74.4)

OG00270.0(67.4 to 72.6)

OG00172.5(69.5 to 75.4)

OG00270.5(67.8 to 73.2)

OG0010.83(0.78 to 0.88)

OG0020.80(0.76 to 0.86)

OG0010.80(0.76 to 0.85)

OG0020.82(0.78 to 0.86)

OG0010.76(0.71 to 0.81)

OG0020.79(0.74 to 0.84)

OG0010.75(0.70 to 0.80)

OG0020.80(0.76 to 0.84)

OG0010.75(0.70 to 0.80)

OG0020.78(0.73 to 0.83)