Study of Efficacy, Safety, and Tolerability of LNA043 in... | NCT04864392 | Trialant
NCT04864392
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Apr 2, 2026Actual
Enrollment
576Actual
Phase
Phase 2
Conditions
Osteoarthritis
Interventions
LNA043
Placebo
Countries
United States
Argentina
Australia
Canada
China
Czechia
Denmark
Estonia
India
Japan
Mexico
Poland
Spain
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04864392
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLNA043A12202
Secondary IDs
ID
Type
Description
Link
2020-004897-22
EudraCT Number
2023-509937-37-00
Registry Identifier
EU CT NUMBER
Brief Title
Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis
Official Title
A 5-year, Randomized, Double-blind, Placebo-controlled, Multi-center Study Assessing the Efficacy, Safety, and Tolerability of Intra-articular Regimens of LNA043 Versus Placebo in Patients With Symptomatic Knee Osteoarthritis
Acronym
ONWARDS
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Mar 2026
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Study early terminated due to lack of effect (did not meet primary/ secondary endpoints). This decision was not linked to safety concerns
Expanded Access Info
No
Start Date
May 31, 2021Actual
Primary Completion Date
Sep 29, 2024Actual
Completion Date
May 29, 2025Actual
First Submitted Date
Feb 26, 2021
First Submission Date that Met QC Criteria
Apr 27, 2021
First Posted Date
Apr 28, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Feb 13, 2026
Results First Submitted that Met QC Criteria
Mar 10, 2026
Results First Posted Date
Mar 30, 2026Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 19, 2025
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Mar 30, 2026Actual
Last Update Submitted Date
Mar 31, 2026
Last Update Posted Date
Apr 2, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis.
Detailed Description
The study was structured as a two-period design:
A 2-year Core Period, followed by
A 3-year Extension Period, consisting of 2 years of continued treatment and 1 year of follow-up, totaling 5 years.
Participants were randomized in a 1:1:1:1:1 ratio into five treatment arms:
LNA043 20 mg Q4w ×3, repeated every 6 months.
LNA043 40 mg ×1 and placebo Q4w ×2, repeated every 6 months.
LNA043 40 mg Q4w ×3 followed six months later by placebo Q4w ×3, repeated every 12 months.
LNA043 40 mg Q4w ×3, repeated every 6 months.
Placebo Q4w ×3, repeated every 6 months.
All injections were administered intra-articularly (i.a.) to the target knee. Placebo injections (saline solution) were used throughout the study to maintain blinding and ensure consistency in injection frequency across arms.
During the Extension Period:
Participants from the 6-month cycle arms continued with a single injection of the same LNA043 dose every 6 months.
Participants from the 12-month cycle arm received LNA043 40 mg every 12 months and placebo every other 6 months.
Participants who received placebo during the Core Period continued with a single injection of the same placebo every 6 months.
The final year of the Extension Period was a no-treatment follow-up phase for all participants.
The study was terminated early following the Week 104 primary endpoint analysis due to lack of effect.There was no safety related reasons for early termination or safety concerns for the subjects in the study.
Conditions Module
Conditions
Osteoarthritis
Keywords
LNA043
knee
arthritis
OA
knees
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
576Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm 1: LNA043 40 mg Q4W x3, Q6m
Experimental
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
Drug: LNA043
Arm 2: LNA043 40 mg Q4W x3, Q12m
Experimental
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Drug: LNA043
Drug: Placebo
Arm 3: LNA043 20 mg Q4W x3, Q6m
Experimental
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
Drug: LNA043
Arm 4: LNA043 40 mg x1, Q6m
Experimental
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
Drug: LNA043
Drug: Placebo
Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LNA043
Drug
LNA043 was administered intra-articularly in various dosing regimens across four active treatment arms:
Arm 1: LNA043 40 mg Q4W ×3, repeated every 6 months
Arm 2: LNA043 40 mg Q4W ×3, followed six months later by placebo Q4W ×3, repeated every 12 months
Arm 3: LNA043 20 mg Q4W ×3, repeated every 6 months
Arm 4: LNA043 40 mg ×1, repeated every 6 months
During the Extension Period, participants continued with either single injections every 6 or 12 months, based on their Core Period assignment.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in Cartilage Thickness in the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee at Week 104
The cartilage thickness in the cMTFC of the target knee was assessed by quantitative Magnetic Resonance Imaging (qMRI). The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness
Baseline, Week 104
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point numeric rating scale (NRS) from 0 (no pain) to 10 (worst imaginable pain). The WOMAC pain subscale was calculated as the sum of the 5 pain items, ranging from 0 to 50, with higher scores indicating worse pain. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Males and females between 40 and 75 years of age
Body mass index (BMI) < 40 kg/m2
Diagnosis of primary tibiofemoral knee OA by standard American College of Rheumatology clinical and radiographic criteria
Key Exclusion Criteria:
Participants with radiographic knee OA K-L grade = 4 on the non-target knee
Arthroscopy of the target knee within the 6 months prior to Screening
Gerwin N, Scotti C, Halleux C, Fornaro M, Elliott J, Zhang Y, Johnson K, Shi J, Walter S, Li Y, Jacobi C, Laplanche N, Belaud M, Paul J, Glowacki G, Peters T, Wharton KA Jr, Vostiar I, Polus F, Kramer I, Guth S, Seroutou A, Choudhury S, Laurent D, Gimbel J, Goldhahn J, Schieker M, Brachat S, Roubenoff R, Kneissel M. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. Nat Med. 2022 Dec;28(12):2633-2645. doi: 10.1038/s41591-022-02059-9. Epub 2022 Dec 1.
See Also Links
Label
URL
A Plain Language Trial Summary is available on www.novctrd.com
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
Participants were recruited from 76 centers across 16 countries. Only participants who completed the Core Period were eligible to enter the Extension Period. One participant from Arm 4 who completed the Core Period did not enter the Extension Period and is therefore not included in the Extension Period counts.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Drug: Placebo
Arm 1: LNA043 40 mg Q4W x3, Q6m
Arm 2: LNA043 40 mg Q4W x3, Q12m
Arm 3: LNA043 20 mg Q4W x3, Q6m
Arm 4: LNA043 40 mg x1, Q6m
Placebo
Drug
Placebo (saline solution for injection) was administered intra-articularly in various regimens to maintain blinding and ensure consistency in injection frequency across all arms:
Arm 2: Placebo Q4W ×3 administered six months after LNA043 Q4W ×3
Arm 4: Two placebo injections following LNA043 40 mg ×1 to complete the 3-injection cycle every 6 months
Placebo Arm: Placebo Q4W ×3 every 6 months throughout the Core and Extension Periods.
In the Extension Period, placebo injections were used to match the frequency of active arms.
Arm 2: LNA043 40 mg Q4W x3, Q12m
Arm 4: LNA043 40 mg x1, Q6m
Placebo
Baseline, Week 104
Change From Baseline in WOMAC Pain Walking on a Flat Surface Item at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point NRS from 0 (no pain) to 10 (worst imaginable pain). Scores were then re-scaled to normalized 0-100.
The change from baseline at Week 104 in WOMAC pain walking on a flat surface item score was assessed, where a negative change indicated improvement.
Baseline, Week 104
Change From Baseline in WOMAC Function Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC functional subscale included 17 questions that measured how OA affected their daily activities including going up and down stairs, sitting, standing, squatting to the floor, walking, getting in a car, shopping, putting on and taking off socks, getting out of bed, lying in bed, bathing, sitting, getting on and off the toilet, heavy domestic duties, and light domestic duties.
Each item was rated on an 11-point NRS from 0 (no limitation) to 10 (extreme limitation). The WOMAC functional subscale was calculated as the sum of the 17 pain items, ranging from 0 to 170, with higher scores indicating more severe limitations. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Total Tibiofemoral Compartments (TFCs) in the Target Knee at Week 104
The cartilage thickness in the total TFC in the target knee was assessed by qMRI. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Medial TFCs in the Target Knee at Week 104
The cartilage thickness in the medial TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Lateral TFCs in the Target Knee at Week 104
The cartilage thickness in the lateral TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Baseline, Week 104
Change From Baseline at Week 104 in the Osteoarthritis Research Society International (OARSI) Physical Performance-based Assessment: 40-meter (4×10m) Fast-paced Walk Test
The OARSI 40-meter (4x10m) fast-paced walk test assessed walking speed and functional mobility over a short distance. Participants were instructed to walk as quickly and safely as possible along a 10-meter walkway, turn around a cone, and repeat the sequence four times for a total of 40 meters. The time taken to complete the 40 meters was recorded. A shorter time indicated better performance.
The change from baseline at Week 104 was assessed. A negative change from baseline indicated improvement in physical function.
Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 30-second Chair Stand Test
The OARSI 30-second chair stand test assessed the number of times a participant stood up from a seated position and sat back down within 30 seconds. A higher number of repetitions reflected better lower limb strength and physical function. The change from baseline was evaluated at Week 104. A positive change from baseline indicated an improvement in physical function.
Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 6-minute Walking Test
This performance-based endpoint assessed submaximal aerobic capacity and functional walking ability. Participants were instructed to walk as far as possible in six minutes along a standardized, level walkway, following the guidelines of the American Thoracic Society. The total distance walked in meters was recorded. A greater distance walked indicated better physical function.
The change from baseline was evaluated at Week 104. A positive change from baseline reflected an improvement in physical function.
Baseline, Week 104
Percentage of Participants With Loss of Medial Minimum Joint Space Width ≥0.70 mm From Baseline at Week 104
Percentage of participants who experienced loss of medial minimum joint space width ≥ 0.70 mm from baseline as measured by X-ray at Week 104
Baseline, Week 104
Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) Status
ADA status was categorized based on baseline and post-baseline results as follows:
Subjects with ADA-negative sample at baseline: Participants with a negative ADA result at baseline.
Subjects with ADA-positive sample at baseline: Participants with a positive ADA result at baseline.
Subjects with ADA-positive NAb sample at baseline: Participants with a positive ADA and neutralizing antibody (NAb) result at baseline.
Subjects with treatment-emergent ADA-positive: Participants with a positive ADA result post-baseline and a negative result at baseline.
Subjects with treatment-emergent ADA-negative: Participants with a negative ADA result at baseline and all post-baseline samples also negative.
Subjects with treatment-emergent ADA-inconclusive: Participants who did not meet any of the above definitions
From baseline up to end of study, assessed up to 3.6 years
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
FG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
FG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
FG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
FG000114 subjects
FG001117 subjects
FG002116 subjects
FG003114 subjects
FG004115 subjects
COMPLETED
FG00081 subjects
FG00191 subjects
FG00292 subjects
FG00391 subjects
FG00484 subjects
NOT COMPLETED
FG00033 subjects
FG00126 subjects
FG00224 subjects
FG00323 subjects
FG00431 subjects
Type
Comment
Reasons
Subject / Guardian Decision
FG00014 subjects
FG00113 subjects
FG00210 subjects
FG00315 subjects
FG00419 subjects
Adverse Event
FG00010 subjects
FG0016 subjects
FG0028 subjects
FG0033 subjects
FG004
Lost to Follow-up
FG0002 subjects
FG0012 subjects
FG0023 subjects
FG0031 subjects
FG004
Physician Decision
FG0004 subjects
FG0011 subjects
FG0021 subjects
FG0032 subjects
FG004
Protocol Deviation
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
FG004
Lack of Efficacy
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG004
Technical Problems
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Extension Period
Type
Comment
Milestone Data
STARTED
FG00081 subjects
FG00191 subjects
FG00292 subjects
FG00390 subjects
FG00484 subjects
COMPLETED
No participants completed the Extension Period due to the early termination of the study
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
NOT COMPLETED
FG00081 subjects
FG00191 subjects
FG00292 subjects
FG00390 subjects
FG004
Type
Comment
Reasons
Study terminated by Sponsor
FG00078 subjects
FG00188 subjects
FG00289 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
BG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
BG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
BG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
BG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000114
BG001117
BG002116
BG003114
BG004115
BG005576
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
BG00060.5± 8.39
BG00160.0± 8.15
BG00259.1± 7.90
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00064
BG00171
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
White
BG00082
BG00180
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
Change From Baseline in Cartilage Thickness in the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee at Week 104
The cartilage thickness in the cMTFC of the target knee was assessed by quantitative Magnetic Resonance Imaging (qMRI). The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
millimiter (mm)
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00076
OG00187
OG00283
OG003
Title
Denominators
Categories
Title
Measurements
OG000-0.29068± 0.030098
OG001-0.30318± 0.028962
OG002-0.26716± 0.029124
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5001
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.02349
Standard Error of the Mean
0.042206
2-Sided
95
-0.07260
0.09442
Superiority
Secondary
Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point numeric rating scale (NRS) from 0 (no pain) to 10 (worst imaginable pain). The WOMAC pain subscale was calculated as the sum of the 5 pain items, ranging from 0 to 50, with higher scores indicating worse pain. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
Score on a Scale
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Secondary
Change From Baseline in WOMAC Pain Walking on a Flat Surface Item at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point NRS from 0 (no pain) to 10 (worst imaginable pain). Scores were then re-scaled to normalized 0-100.
The change from baseline at Week 104 in WOMAC pain walking on a flat surface item score was assessed, where a negative change indicated improvement.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
Score on a Scale
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Secondary
Change From Baseline in WOMAC Function Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC functional subscale included 17 questions that measured how OA affected their daily activities including going up and down stairs, sitting, standing, squatting to the floor, walking, getting in a car, shopping, putting on and taking off socks, getting out of bed, lying in bed, bathing, sitting, getting on and off the toilet, heavy domestic duties, and light domestic duties.
Each item was rated on an 11-point NRS from 0 (no limitation) to 10 (extreme limitation). The WOMAC functional subscale was calculated as the sum of the 17 pain items, ranging from 0 to 170, with higher scores indicating more severe limitations. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
Score on a Scale
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Secondary
Change From Baseline in Cartilage Thickness in the Total Tibiofemoral Compartments (TFCs) in the Target Knee at Week 104
The cartilage thickness in the total TFC in the target knee was assessed by qMRI. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
milimiter (mm)
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Secondary
Change From Baseline in Cartilage Thickness in the Medial TFCs in the Target Knee at Week 104
The cartilage thickness in the medial TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
milimiter (mm)
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Secondary
Change From Baseline in Cartilage Thickness in the Lateral TFCs in the Target Knee at Week 104
The cartilage thickness in the lateral TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
milimiter (mm)
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Secondary
Change From Baseline at Week 104 in the Osteoarthritis Research Society International (OARSI) Physical Performance-based Assessment: 40-meter (4×10m) Fast-paced Walk Test
The OARSI 40-meter (4x10m) fast-paced walk test assessed walking speed and functional mobility over a short distance. Participants were instructed to walk as quickly and safely as possible along a 10-meter walkway, turn around a cone, and repeat the sequence four times for a total of 40 meters. The time taken to complete the 40 meters was recorded. A shorter time indicated better performance.
The change from baseline at Week 104 was assessed. A negative change from baseline indicated improvement in physical function.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
Seconds
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Secondary
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 30-second Chair Stand Test
The OARSI 30-second chair stand test assessed the number of times a participant stood up from a seated position and sat back down within 30 seconds. A higher number of repetitions reflected better lower limb strength and physical function. The change from baseline was evaluated at Week 104. A positive change from baseline indicated an improvement in physical function.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
Number of Repetitions
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Secondary
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 6-minute Walking Test
This performance-based endpoint assessed submaximal aerobic capacity and functional walking ability. Participants were instructed to walk as far as possible in six minutes along a standardized, level walkway, following the guidelines of the American Thoracic Society. The total distance walked in meters was recorded. A greater distance walked indicated better physical function.
The change from baseline was evaluated at Week 104. A positive change from baseline reflected an improvement in physical function.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Least Squares Mean
Standard Error
meters
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
Secondary
Percentage of Participants With Loss of Medial Minimum Joint Space Width ≥0.70 mm From Baseline at Week 104
Percentage of participants who experienced loss of medial minimum joint space width ≥ 0.70 mm from baseline as measured by X-ray at Week 104
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Only participants with measures both at baseline and at Week 104 were included in this analysis
Posted
Number
95% Confidence Interval
Percentage of participants
Baseline, Week 104
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
Secondary
Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) Status
ADA status was categorized based on baseline and post-baseline results as follows:
Subjects with ADA-negative sample at baseline: Participants with a negative ADA result at baseline.
Subjects with ADA-positive sample at baseline: Participants with a positive ADA result at baseline.
Subjects with ADA-positive NAb sample at baseline: Participants with a positive ADA and neutralizing antibody (NAb) result at baseline.
Subjects with treatment-emergent ADA-positive: Participants with a positive ADA result post-baseline and a negative result at baseline.
Subjects with treatment-emergent ADA-negative: Participants with a negative ADA result at baseline and all post-baseline samples also negative.
Subjects with treatment-emergent ADA-inconclusive: Participants who did not meet any of the above definitions
All participants in the Immunogenicity prevalence set with a non-missing baseline ADA sample and at least one non-missing post-baseline ADA sample.
Posted
Count of Participants
Participants
From baseline up to end of study, assessed up to 3.6 years
ID
Title
Description
OG000
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG001
Arm 2: LNA043 40 mg x3, Q12m
Time Frame
From start of treatment to end of study, assessed up to 3.6 years
Description
The safety data presented reflects cumulative data (entire study period) from both Core and Extension Periods
All-Cause Mortality Comment
Not provided
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
Arm 1: LNA043 40 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
0
114
17
114
69
114
EG001
Arm 2: LNA043 40 mg x3, Q12m
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
0
117
13
117
69
117
EG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
1
116
13
116
77
116
EG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
1
114
11
114
78
114
EG004
Any LNA043
Combined 4 LNA043 treatment groups
Arm 1: LNA043 40 mg x3, Q6m
Arm 2: LNA043 40 mg x3, Q12m
Arm 3: LNA043 20 mg x3, Q6m
Arm 4: LNA043 40 mg x1, Q6m
2
461
54
461
293
461
EG005
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
1
115
13
115
68
115
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrial fibrillation
Cardiac disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG0032 affected114 at risk
EG0042 affected461 at risk
EG0050 affected115 at risk
Cardiac arrest
Cardiac disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA (28.0)
Systematic Assessment
EG0002 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Cataract
Eye disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Incarcerated umbilical hernia
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Umbilical hernia
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Appendicitis
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Appendicitis perforated
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Arthritis bacterial
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
COVID-19
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Diverticulitis intestinal perforated
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Retroperitoneal abscess
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Septic arthritis staphylococcal
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Meniscus injury
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Muscle rupture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Patella fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Radius fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Wrist fracture
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Foot deformity
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Joint range of motion decreased
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0002 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Adenocarcinoma of colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0021 affected116 at risk
EG003
Breast cancer in situ
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Chondromatosis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Clear cell renal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Colorectal adenoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Endometrial cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Gallbladder adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Intraductal papillary breast neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Invasive ductal breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Lung adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Lung neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Meningioma benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Ovarian cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Papillary thyroid cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Thyroid cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Dementia Alzheimer's type
Nervous system disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Urethral caruncle
Renal and urinary disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0021 affected116 at risk
EG003
Breast enlargement
Reproductive system and breast disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Cystocele
Reproductive system and breast disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Schnitzler's syndrome
Skin and subcutaneous tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Embolism venous
Vascular disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0011 affected117 at risk
EG0020 affected116 at risk
EG003
Hypertension
Vascular disorders
MedDRA (28.0)
Systematic Assessment
EG0000 affected114 at risk
EG0010 affected117 at risk
EG0020 affected116 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA (28.0)
Systematic Assessment
EG0003 affected114 at risk
EG0013 affected117 at risk
EG0022 affected116 at risk
EG0037 affected114 at risk
EG00415 affected461 at risk
EG0054 affected115 at risk
Influenza like illness
General disorders
MedDRA (28.0)
Systematic Assessment
EG0004 affected114 at risk
EG0015 affected117 at risk
EG0027 affected116 at risk
EG003
Injection site joint pain
General disorders
MedDRA (28.0)
Systematic Assessment
EG0006 affected114 at risk
EG0018 affected117 at risk
EG0029 affected116 at risk
EG003
Injection site joint swelling
General disorders
MedDRA (28.0)
Systematic Assessment
EG00010 affected114 at risk
EG0019 affected117 at risk
EG0028 affected116 at risk
EG003
COVID-19
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG00027 affected114 at risk
EG00120 affected117 at risk
EG00216 affected116 at risk
EG003
Influenza
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0006 affected114 at risk
EG0016 affected117 at risk
EG0026 affected116 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG00013 affected114 at risk
EG00122 affected117 at risk
EG00219 affected116 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0004 affected114 at risk
EG0015 affected117 at risk
EG0026 affected116 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (28.0)
Systematic Assessment
EG0004 affected114 at risk
EG0011 affected117 at risk
EG0025 affected116 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0004 affected114 at risk
EG0013 affected117 at risk
EG0028 affected116 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (28.0)
Systematic Assessment
EG0003 affected114 at risk
EG0013 affected117 at risk
EG0026 affected116 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG00017 affected114 at risk
EG00124 affected117 at risk
EG00221 affected116 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0004 affected114 at risk
EG0015 affected117 at risk
EG0028 affected116 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0005 affected114 at risk
EG0017 affected117 at risk
EG0024 affected116 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (28.0)
Systematic Assessment
EG0005 affected114 at risk
EG0013 affected117 at risk
EG0023 affected116 at risk
EG003
Headache
Nervous system disorders
MedDRA (28.0)
Systematic Assessment
EG0006 affected114 at risk
EG0015 affected117 at risk
EG0023 affected116 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (28.0)
Systematic Assessment
EG0001 affected114 at risk
EG0014 affected117 at risk
EG0023 affected116 at risk
EG003
Hypertension
Vascular disorders
MedDRA (28.0)
Systematic Assessment
EG0002 affected114 at risk
EG0017 affected117 at risk
EG0027 affected116 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.03599
Standard Error of the Mean
0.041461
2-Sided
95
-0.15181
0.07983
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.00003
Standard Error of the Mean
0.041373
2-Sided
95
-0.11555
0.11560
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at a =0.05.
Least Squares Mean
0.00997
Standard Error of the Mean
0.041289
2-Sided
95
-0.10538
0.12531
Superiority
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00073
OG00181
OG00278
OG00379
OG00473
Title
Denominators
Categories
Title
Measurements
OG000-27.77± 2.226
OG001-32.53± 2.166
OG002-29.96± 2.170
OG003-30.46± 2.153
OG004-29.98± 2.208
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5002
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Sqaures Mean
2.21
Standard Error of the Mean
3.136
2-Sided
95
-6.83
11.25
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.4989
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-2.55
Standard Error of the Mean
3.090
2-Sided
95
-11.45
6.36
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.02
Standard Error of the Mean
3.101
2-Sided
95
-8.91
8.96
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Sqaures Mean
-0.48
Standard Error of the Mean
3.083
2-Sided
95
-9.36
8.41
Superiority
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00073
OG00181
OG00278
OG00379
OG00473
Title
Denominators
Categories
Title
Measurements
OG000-26.43± 2.477
OG001-31.09± 2.399
OG002-28.09± 2.413
OG003-27.95± 2.394
OG004-28.91± 2.462
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5002
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Sqaures Mean
2.48
Standard Error of the Mean
3.495
2-Sided
95
-7.57
12.53
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-2.18
Standard Error of the Mean
3.431
2-Sided
95
-12.04
7.69
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.82
Standard Error of the Mean
3.459
2-Sided
95
-9.13
10.77
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Sqaures Mean
0.96
Standard Error of the Mean
3.432
2-Sided
95
-8.91
10.83
Superiority
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00073
OG00181
OG00278
OG00379
OG00473
Title
Denominators
Categories
Title
Measurements
OG000-26.43± 2.477
OG001-31.09± 2.399
OG002-28.09± 2.413
OG003-27.95± 2.394
OG004-28.91± 2.462
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5002
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-2.18
Standard Error of the Mean
3.431
2-Sided
95
-12.04
7.69
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-2.18
Standard Error of the Mean
3.431
2-Sided
95
-12.04
7.69
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.82
Standard Error of the Mean
3.459
2-Sided
95
-9.13
10.77
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.96
Standard Error of the Mean
3.432
2-Sided
95
-8.91
10.83
Superiority
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00076
OG00187
OG00283
OG00386
OG00482
Title
Denominators
Categories
Title
Measurements
OG000-0.10038± 0.006428
OG001-0.10412± 0.006157
OG002-0.09345± 0.006231
OG003-0.09619± 0.006151
OG004-0.09912± 0.006288
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.00126
Standard Error of the Mean
0.008999
2-Sided
95
-0.02644
0.02392
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5001
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.00126
Standard Error of the Mean
0.008999
2-Sided
95
-0.02644
0.02392
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.4997
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.00567
Standard Error of the Mean
0.008827
2-Sided
95
-0.01903
0.03037
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.00293
Standard Error of the Mean
0.008815
2-Sided
95
-0.02174
0.02759
Superiority
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00076
OG00187
OG00283
OG00386
OG00482
Title
Denominators
Categories
Title
Measurements
OG000-0.22475± 0.018161
OG001-0.23277± 0.017442
OG002-0.20151± 0.017551
OG003-0.20537± 0.017364
OG004-0.21689± 0.017788
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.00786
Standard Error of the Mean
0.025453
2-Sided
95
-0.07883
0.06312
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5003
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.01588
Standard Error of the Mean
0.024966
2-Sided
95
-0.08549
0.05374
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.4998
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.01538
Standard Error of the Mean
0.024932
2-Sided
95
-0.05414
0.03037
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.01152
Standard Error of the Mean
0.024881
2-Sided
95
-0.05786
0.08090
Superiority
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00077
OG00187
OG00283
OG00386
OG00482
Title
Denominators
Categories
Title
Measurements
OG000-0.15194± 0.012873
OG001-0.16868± 0.012377
OG002-0.14826± 0.012539
OG003-0.16152± 0.012401
OG004-0.14920± 0.012641
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.00274
Standard Error of the Mean
0.018046
2-Sided
95
-0.05374
0.04827
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5347
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.01948
Standard Error of the Mean
0.017698
2-Sided
95
-0.06950
0.03054
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.00094
Standard Error of the Mean
0.017776
2-Sided
95
-0.04930
0.05118
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5004
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.01232
Standard Error of the Mean
0.017733
2-Sided
95
-0.06243
0.03780
Superiority
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00071
OG00178
OG00278
OG00381
OG00470
Title
Denominators
Categories
Title
Measurements
OG000-0.691± 1.7057
OG001-1.455± 1.6486
OG002-1.846± 1.6514
OG003-2.219± 1.6248
OG004-3.751± 1.7030
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5541
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
3.059
Standard Error of the Mean
2.4079
2-Sided
95
-3.871
9.990
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.5063
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
2.296
Standard Error of the Mean
2.3733
2-Sided
95
-4.536
9.127
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.5009
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
1.905
Standard Error of the Mean
2.3756
2-Sided
95
-4.933
8.742
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5001
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
1.532
Standard Error of the Mean
2.3525
2-Sided
95
-5.239
8.303
Superiority
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00071
OG00178
OG00277
OG00380
OG00470
Title
Denominators
Categories
Title
Measurements
OG0002.1± 0.38
OG0012.1± 0.37
OG0022.0± 0.37
OG0032.1± 0.36
OG0041.4± 0.38
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.4415
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.7
Standard Error of the Mean
0.54
2-Sided
95
-0.8
2.3
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.4541
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.7
Standard Error of the Mean
0.53
2-Sided
95
-0.9
2.3
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.4632
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.7
Standard Error of the Mean
0.54
2-Sided
95
-0.9
2.2
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.4241
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
0.8
Standard Error of the Mean
0.53
2-Sided
95
-0.8
2.3
Superiority
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00070
OG00178
OG00278
OG00381
OG00469
Title
Denominators
Categories
Title
Measurements
OG00032.7± 9.81
OG00145.9± 9.39
OG00242.0± 9.37
OG00324.4± 9.33
OG00424.7± 9.82
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
8.0
Standard Error of the Mean
13.85
2-Sided
95
-31.7
47.6
Superiority
OG001
OG004
Mixed-effect model repeated measures
0.3330
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
21.2
Standard Error of the Mean
13.61
2-Sided
95
-17.7
60.2
Superiority
OG002
OG004
Mixed-effect model repeated measures
0.4359
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
17.3
Standard Error of the Mean
13.57
2-Sided
95
-21.6
56.1
Superiority
OG003
OG004
Mixed-effect model repeated measures
0.5000
The significance of the treatment effects for LNA043 regimens at Week 104 was determined from the pairwise comparisons using the Dunnett test performed between LNA043 regimens and placebo at alpha =0.05 (one-sided, family-wise type-I-error).
Least Squares Mean
-0.3
Standard Error of the Mean
13.62
2-Sided
95
-39.3
38.7
Superiority
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.
Units
Counts
Participants
OG00080
OG00189
OG00291
OG00391
OG00485
Title
Denominators
Categories
Title
Measurements
OG00010.0(4.7 to 19.3)
OG0019.0(4.2 to 17.4)
OG00214.3(8.1 to 23.6)
OG0039.9(4.9 to 18.4)
OG00412.9(6.9 to 22.4)
Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.
OG002
Arm 3: LNA043 20 mg x3, Q6m
Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.
OG003
Arm 4: LNA043 40 mg x1, Q6m
Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.
OG004
Placebo x3, Q6m
Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years.