Study of Safety, Tolerability, Preliminary Efficacy of In... | NCT03275064 | Trialant
NCT03275064
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Apr 21, 2026Actual
Enrollment
142Actual
Phase
Phase 2
Conditions
Osteoarthritis
Interventions
LNA043
Placebo
Countries
United States
Czechia
Denmark
Protocol Section
Identification Module
NCT ID
NCT03275064
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLNA043X2202
Secondary IDs
ID
Type
Description
Link
2016-004052-30
EudraCT Number
CTI-194705
Other Identifier
Japic CTI
Brief Title
Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis.
Official Title
A Two-part, Randomized, Placebo-controlled, Patient and Investigator Blinded, Study Investigating the Safety, Tolerability and Preliminary Efficacy of Intra-articular LNA043 Injections in Regenerating the Articular Cartilage of the Knee in Patients With Articular Cartilage Lesions (Part A) and in Patients With Knee Osteoarthritis (Part B).
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Mar 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 12, 2017Actual
Primary Completion Date
Sep 6, 2022Actual
Completion Date
Sep 6, 2022Actual
First Submitted Date
Aug 29, 2017
First Submission Date that Met QC Criteria
Sep 5, 2017
First Posted Date
Sep 7, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Sep 4, 2023
Results First Submitted that Met QC Criteria
Jan 23, 2024
Results First Posted Date
Feb 14, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 30, 2026
Last Update Posted Date
Apr 21, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
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
The purpose of this two-part study is to assess the efficacy, safety and tolerability of multiple intra-articular (i.a.) injections of LNA043, in regenerating the articular surface in patients with cartilage lesions of the knee (Part A) and knee osteoarthritis (Part B).
Detailed Description
There was a 30 day screening period for both Part A and Part B. In Part A, participants were randomized to 3:1 ratio and received an injection of LNA043 (20 mg in 3 ml) or matching placebo (3 ml) on Days 1, 8,15 and 22 and were monitored in clinic for 3 hours after each injection followed by telephone calls 48 hours after injection. Participants returned to the clinic on Days 50, 106, 190 and 365 for follow up visits. MRIs, safety assessments and pharmacokinetics were assessed at selected clinic visits.
In Part B, this study aimed at further evaluating the cartilage anabolic activity of LNA043 in a more severe knee OA population, and to explore the safety and efficacy of a higher dose.
In Part B, participants were randomized to LNA043 20 mg, LNA043 40 mg or matching placebo according in a 1:1:1 ratio. Injections were given in clinic on Days 1, 29, 57 and 85 and participants were monitored in clinic for 3 hours after each injection followed by telephone calls 48 hours after injection. Participants returned to the clinic on Days 113,197 and 365 (end of study) for follow up visits. MRIs, safety assessments and pharmacokinetics were assessed at selected clinic visits.
Conditions Module
Conditions
Osteoarthritis
Keywords
Articular cartilage
partial thickness cartilage lesion
knee cartilage
regeneration
osteoarthritis
adult
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
142Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
LNA043 40 mg Part B
Experimental
LNA043 40 mg Part B
Biological: LNA043
LNA043 20 mg Part B
Experimental
LNA043 20 mg Part B
Biological: LNA043
LNA043 20 mg Part A
Experimental
LNA043 20 mg Part A
Biological: LNA043
Placebo Part A
Placebo Comparator
Placebo Part A
Other: Placebo
Placebo Part B
Placebo Comparator
Placebo Part B
Other: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LNA043
Biological
LNA043 intra-articular injection
LNA043 20 mg Part A
LNA043 20 mg Part B
LNA043 40 mg Part B
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in Articular Cartilage Collagen Organization in the Overall Cartilage (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by Magnetic Resonance Imaging (MRI) from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.
Baseline up to Week 16, Week 28
Change From Baseline in Articular Cartilage Collagen Organization in the Deep Cartilage Layer (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.
Baseline up to Week 16, Week 28
Change From Baseline in Articular Cartilage Collagen Organization in the Superficial Cartilage Layer (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality).The area of interest is the focal cartilage lesion.
Baseline up to Week 16, Week 28
Change From Baseline of LNA043 to Placebo in Cartilage Volume in the Femoral Medial Index Region (mm3) - Part B
MRI based quantitative assessment using an automated segmentation algorithm
Baseline, Week 29, Week 53
Change From Baseline of LNA043 to Placebo in Cartilage Thickness in the Femoral Medial Index Region (mm) - Part B
MRI based quantitative assessment using an automated segmentation algorithm.
Baseline, Week 29, Week 53
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline of LNA043 to Placebo in Cartilage Defect Volume (mm^3) for Both Groups of Patients (Femoral and Patellar Lesions) - Part A
Cartilage volume data were generated from the manual segmentation of the cartilage defect that was identified in MR images.
Baseline up to Week 16, Week 28
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Overall Part B
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria Part A
Patient was ≥18 and ≤55 years old at time of screening.
Patient had a body mass index (BMI) <30 kg/m2 at screening,
Patient had a symptomatic, single, articular cartilage defect of one knee, grade II or IIIA according to the ICRS classification, localized to either the femoral condyles/femoral trochlea or to the patella, based on MRI or arthroscopy performed within 9 months before screening visit and confirmed by screening 3T MRI.
Patient had an onset of pain and impairment of function between two (2) months and two (2) years before screening.
Patient had a grade 2 or 3 OA of the knee with Joint Space Width (JSW) 2-4 mm evaluated with X-Ray at screening
Inclusion criteria Part B
Patient was ≥18 and ≤75 years old at time of screening.
Patient had a body mass index (BMI) ≤ 35 kg/m2 at screening
Diagnosis of femorotibial osteoarthritis (OA) in the target knee by standard American College of Rheumatology (ACR) criteria at study start (clinical AND radiographic criteria)
Patient must have had symptomatic disease predominantly in one (the index) knee, with minimal or no symptoms in the contralateral knee. Symptomatic disease is defined as having pain in the knee more than 50% of the days during the last 3 months from screening.
Patient had a K&L grade 2 or 3 OA of the knee with JSW 2.00-4.00 mm (X=0.225) fixed position evaluated with X-Ray by the Central Reader at screening.
Exclusion criteria Part A & B
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 15 days after stopping of investigational drug.
Patient had surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% (Note: prior diagnostic arthroscopy with debridement and lavage, <50% meniscectomy, lateral release, patellar realignment, medial patellofemoral ligament reconstruction are acceptable if performed at least 2 months prior to screening; anteriorcruciate ligament reconstrucion is acceptable if performed 12 months prior to screening, or less if restoration of joint function is evident, and agreed by the sponsor).
Patient had an unstable target knee joint or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
Prohibited medication updated with reference to dosing (formerly screening).
Exclusion Criteria Part A only
Regular smokers (> 5 cigarettes/day). Urine cotinine levels will be measured during screening for all patients. Regular smokers will be defined as any patient who reports tobacco use of > 5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.
Patient had radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2 based on X-ray evaluation performed within 9 months from screening.
Patient had patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation performed within 9 months from screening
Patient had malalignment (valgus- or varus-deformity) in the target knee ≥ 5° based on X-ray evaluation performed within 9 months from screening. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.
Exclusion Criteria Part B only
Regular smokers (> 10 cigarettes/day).
Clinical signs of inflammation (i.e., redness) in the target knee.
History of knee replacement (unilateral or total) in either knee.
Presence of severe hip OA conditioning lower limb function according to PI's evaluation.
Nephrotic syndrome and/or significant proteinuria
History of coagulopathy or medical condition requiring anticoagulation which would preclude knee injection
Patient had malalignment (valgus- or varus-deformity) in the target knee ≥ 7.5° based on X-ray evaluation. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Arizona Research
Phoenix
Arizona
85053
United States
Scott A Hacker MD Medical Group d b a Horizon Clinical Res
References Module
Citations
Not provided
See Also Links
Label
URL
A Plain Language Trial Summary is available on 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.
A total of 142 participants were randomized, but only 141 received treatment. One participant in Part B was discontinued due to poor veins that were not adequate for blood samples.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
FG001
Placebo Part A
Periods
Title
Milestones
Reasons Not Completed
Treatment Period Part A and Part B
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Dec 22, 2020
Sep 4, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Sweden
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
A total of 142 participants were randomized, but only 141 received treatment. One participant in Part B was discontinued due to poor veins that were not adequate for blood samples.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Placebo
Other
Placebo intra-articular injection
Placebo Part A
Placebo Part B
Overview of Number of Participants With Adverse Events and Serious Adverse Events for Part A and Part B
Treatment emergent other and serious adverse events (TEAE and TESAE) period:
Part A: Baseline up to Day 50 (included 30 day safety follow-up Part B: Baseline up to Day 113 (included 30 day safety follow-up)
Long term Follow-UP period:
Part A: Day 51 to Day 365 Part B: Day 114 to Day 365
Baseline up to end of post treatment follow-up
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Baseline, Week 29, Week 53
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Deep Part B
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Baseline, Week 29, Week 53
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Superficial Part B
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Baseline, Week 29, Week 53
Incidence of Immunogenicity (IG) Part A
A validated ligand binding assay were used for the detection of anti-LNA043 antibodies, and cross-reactivity to ANGPTL3 and ANGPTL4.
Week 1,3,8,16,28
Incidence of Immunogenicity (IG) Part B
A validated ligand binding assay were used for the detection of anti-LNA043 antibodies, and cross-reactivity to ANGPTL3 and ANGPTL4.
Week 1,5,9,13,17,29,53
Serum Concentrations of LNA043 - Part A
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in serum. Concentrations below the LLOQ were reported as "zero"
Validated bioanalytical assays were used to determine ANGPTL3 in serum with an LLOQ of 2.13 ng/mL. Concentrations below the LLOQ were reported as "zero"
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in synovial fluid. Concentrations below the LLOQ were reported as "zero".
Weeks 1,2,3,4: 0 hour (pre-dose)
Synovial Fluid Concentrations of ANGPTL3 - Part A
Validated bioanalytical assays were used to determine ANGPTL3 in synovial fluid with an LLOQ of 2.74 ng/mL. Concentrations below the LLOQ were reported as "zero".
Weeks 1,2,3,4: 0 hour (pre-dose)
Serum Concentrations of LNA043 - Part B
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in serum. Concentrations below the LLOQ were reported as "zero
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
Serum Concentrations of ANGPTL3 - Part B
Validated bioanalytical assays were used to determine ANGPTL3 in serum with an LLOQ of 2.13 ng/mL. Concentrations below the LLOQ were reported as "zero".
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
Synovial Fluid Concentrations of LNA043 Part B
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in synovial fluid. Concentrations below the LLOQ were reported as "zero".
Weeks 1,5.9.13: 0 hour (pre-dose)
Synovial Fluid Concentrations of ANGPTL3 - Part B
Validated bioanalytical assays were used to determine ANGPTL3 in synovial fluid with an LLOQ of 2.74 ng/mL. Concentrations below the LLOQ were reported as "zero".
Weeks 1,5.9.13: 0 hour (pre-dose)
La Mesa
California
91942
United States
Northern California Research
Sacramento
California
95821
United States
Panax Clinical Research
Miami Lakes
Florida
33014
United States
Precision Clinical Research LLC
Sunrise
Florida
33351
United States
Clinical Research of West Florida Inc
Tampa
Florida
33606
United States
St Lukes Intermountain Research Center
Boise
Idaho
83702
United States
Midwest Orthopedics At Rush
Chicago
Illinois
60612
United States
Sundance Clinical Research LLC
St Louis
Missouri
63141
United States
LV Research
Las Vegas
Nevada
89119
United States
Temple University
Philadelphia
Pennsylvania
19140
United States
Novartis Investigative Site
Brno
Czech Republic
66250
Czechia
Novartis Investigative Site
Mladá Boleslav
Czech Republic
29301
Czechia
Novartis Investigative Site
Kladno
272 59
Czechia
Novartis Investigative Site
Kolín
280 02
Czechia
Novartis Investigative Site
Pardubice
53002
Czechia
Novartis Investigative Site
Prague
190 00
Czechia
Novartis Investigative Site
Aarhus N
8200
Denmark
Novartis Investigative Site
Hvidovre
2650
Denmark
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
FG002
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
FG003
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
FG004
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
FG00043 subjects
FG00115 subjects
FG00227 subjects
FG00327 subjects
FG00429 subjects
Patient d/c Treatment But Continued Into Follow up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
COMPLETED
FG00043 subjects
FG00115 subjects
FG00227 subjects
FG00326 subjects
FG00429 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
Type
Comment
Reasons
PI decision based on poor veins for blood sampling
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
Post-treatment Follow-up Parts A and B
Type
Comment
Milestone Data
STARTED
FG00043 subjects
FG00115 subjects
FG00227 subjects
FG00326 subjects
FG00429 subjects
COMPLETED
FG00042 subjects
FG00115 subjects
FG00224 subjects
FG00325 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0023 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
BG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
BG002
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
BG003
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
BG004
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00043
BG00115
BG00227
BG00327
BG00429
BG005141
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Category breakdown for age differed for Part A and Part B
Number
participants
Title
Denominators
Categories
≥18 and ≤55 years Part A only
ParticipantsBG00043
ParticipantsBG00115
ParticipantsBG0020
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00043
ParticipantsBG00115
ParticipantsBG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Asian
ParticipantsBG00043
ParticipantsBG00115
ParticipantsBG002
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 Articular Cartilage Collagen Organization in the Overall Cartilage (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by Magnetic Resonance Imaging (MRI) from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline up to Week 16, Week 28
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG00041
OG00115
Title
Denominators
Categories
Week 16
ParticipantsOG00041
ParticipantsOG00114
Title
Measurements
OG0003.02± 9.66
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
OG001
Week 16
Mixed Models Analysis
Mean Difference (Net)
0.48
2-Sided
90
-30.73
31.69
Superiority
OG000
OG001
Week 28
Mixed Models Analysis
Primary
Change From Baseline in Articular Cartilage Collagen Organization in the Deep Cartilage Layer (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline up to Week 16, Week 28
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Primary
Change From Baseline in Articular Cartilage Collagen Organization in the Superficial Cartilage Layer (Femoral and Patellar Lesions) - Part A
Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality).The area of interest is the focal cartilage lesion.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline up to Week 16, Week 28
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Primary
Change From Baseline of LNA043 to Placebo in Cartilage Volume in the Femoral Medial Index Region (mm3) - Part B
MRI based quantitative assessment using an automated segmentation algorithm
Pharmacodynamic (PD) analysis set: participants with baseline and at least one follow-up MRI assessments for volume of sufficient quality
Posted
Mean
Standard Error
mm^3
Baseline, Week 29, Week 53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Primary
Change From Baseline of LNA043 to Placebo in Cartilage Thickness in the Femoral Medial Index Region (mm) - Part B
MRI based quantitative assessment using an automated segmentation algorithm.
Pharmacodynamic (PD) analysis set: participants with baseline and at least one follow-up MRI assessments for thickness of sufficient quality
Posted
Mean
Standard Error
mm
Baseline, Week 29, Week 53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Secondary
Change From Baseline of LNA043 to Placebo in Cartilage Defect Volume (mm^3) for Both Groups of Patients (Femoral and Patellar Lesions) - Part A
Cartilage volume data were generated from the manual segmentation of the cartilage defect that was identified in MR images.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
mm^3
Baseline up to Week 16, Week 28
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Overall Part B
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline, Week 29, Week 53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Secondary
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Deep Part B
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline, Week 29, Week 53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Secondary
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Superficial Part B
Collagen fibril organisation in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the femoral medial index region comprising the anterior, central and posterior aspects of the femoral condyle.
Pharmacodynamic (PD) analysis set: Subjects with available PD data
Posted
Mean
Standard Error
ms
Baseline, Week 29, Week 53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Secondary
Incidence of Immunogenicity (IG) Part A
A validated ligand binding assay were used for the detection of anti-LNA043 antibodies, and cross-reactivity to ANGPTL3 and ANGPTL4.
Safety analysis set
Posted
Number
participants
Week 1,3,8,16,28
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Secondary
Incidence of Immunogenicity (IG) Part B
A validated ligand binding assay were used for the detection of anti-LNA043 antibodies, and cross-reactivity to ANGPTL3 and ANGPTL4.
Safety analysis set
Posted
Number
participants
Week 1,5,9,13,17,29,53
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Units
Counts
Secondary
Serum Concentrations of LNA043 - Part A
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in serum. Concentrations below the LLOQ were reported as "zero"
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
Units
Counts
Participants
OG000
Secondary
Serum Concentrations of ANGPTL3 - Part A
Validated bioanalytical assays were used to determine ANGPTL3 in serum with an LLOQ of 2.13 ng/mL. Concentrations below the LLOQ were reported as "zero"
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Secondary
Synovial Fluid Concentrations of LNA043 - Part A
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in synovial fluid. Concentrations below the LLOQ were reported as "zero".
LNA043 Stability in synovial fluid could not be demonstrated. Consequently, the assay was not considered suitable for the determination of LNA043 in synovial fluid collected in Part A and no reportable concentrations of LNA043 in synovial fluid are available in Part A, samples were never assayed and so data are not available for LNA043 concentrations in synovial fluid for Part A.
Posted
Weeks 1,2,3,4: 0 hour (pre-dose)
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
Units
Counts
Participants
OG000
Secondary
Synovial Fluid Concentrations of ANGPTL3 - Part A
Validated bioanalytical assays were used to determine ANGPTL3 in synovial fluid with an LLOQ of 2.74 ng/mL. Concentrations below the LLOQ were reported as "zero".
Pharmacokinetic analysis set
Posted
Mean
Standard Deviation
ng/mL
Weeks 1,2,3,4: 0 hour (pre-dose)
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
Units
Counts
Participants
OG000
Secondary
Serum Concentrations of LNA043 - Part B
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in serum. Concentrations below the LLOQ were reported as "zero
Pharmacokinetic analysis set
Posted
Mean
Standard Deviation
ng/mL
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
Units
Counts
Participants
OG000
Secondary
Serum Concentrations of ANGPTL3 - Part B
Validated bioanalytical assays were used to determine ANGPTL3 in serum with an LLOQ of 2.13 ng/mL. Concentrations below the LLOQ were reported as "zero".
Pharmacokinetic analysis set
Posted
Mean
Standard Deviation
ng/mL
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Secondary
Synovial Fluid Concentrations of LNA043 Part B
Concentrations for LNA043 were determined by a validated LC-MS/MS method; the anticipated LLOQ was 10ng/mL in synovial fluid. Concentrations below the LLOQ were reported as "zero".
Pharmacokinetic analysis set
Posted
Mean
Standard Deviation
ng/mL
Weeks 1,5.9.13: 0 hour (pre-dose)
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
Units
Counts
Participants
OG000
Secondary
Synovial Fluid Concentrations of ANGPTL3 - Part B
Validated bioanalytical assays were used to determine ANGPTL3 in synovial fluid with an LLOQ of 2.74 ng/mL. Concentrations below the LLOQ were reported as "zero".
Pharmacokinetic analysis set
Posted
Mean
Standard Deviation
ng/mL
Weeks 1,5.9.13: 0 hour (pre-dose)
ID
Title
Description
OG000
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG001
LNA043 40 mg Part B
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG002
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis
Units
Primary
Overview of Number of Participants With Adverse Events and Serious Adverse Events for Part A and Part B
Treatment emergent other and serious adverse events (TEAE and TESAE) period:
Part A: Baseline up to Day 50 (included 30 day safety follow-up Part B: Baseline up to Day 113 (included 30 day safety follow-up)
Long term Follow-UP period:
Part A: Day 51 to Day 365 Part B: Day 114 to Day 365
Safety analysis set
Posted
Number
participants
Baseline up to end of post treatment follow-up
ID
Title
Description
OG000
LNA043 20 mg Part A
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
OG001
Placebo Part A
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee
OG002
LNA043 20 mg Part B
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG003
Time Frame
Treatment emergent (TE) averse events: Part A: Baseline up to Day 50 (including 30 day safety follow-up post last dose) Part B: Baseline up to Day 113 (including 30 day safety follow-up post last dose) Long term Follow-Up (FU) period: Part A: Day 51 to Day 365 Part B: Day 114 to Day 365
Description
Not provided
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
LNA043 20 mg Part A - TE
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
Treatment Emergent (TE) AEs are reported Baseline up to Day 50.
0
43
0
43
19
43
EG001
Placebo Part A - TE
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
Treatment Emergent (TE) AEs are reported Baseline up to Day 50.
0
15
0
15
7
15
EG002
LNA043 20 mg Part B - TE
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
Treatment Emergent (TE) AEs are reported Baseline up to Day 113.
0
27
1
27
6
27
EG003
LNA043 40 mg Part B - TE
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
Treatment Emergent (TE) AEs are reported Baseline up to Day 113.
0
27
0
27
15
27
EG004
Placebo Part B - TE
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
Treatment Emergent (TE) AEs are reported Baseline up to Day 113.
0
29
0
29
10
29
EG005
LNA043 20 mg Part A - FU
Part A: a single intra-articular injection of 20 mg LNA043 was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
AEs in long term Follow-Up (FU) period are reported form Day 51 to Day 365.
0
43
2
43
16
43
EG006
Placebo Part A - FU
Part A: a single intra-articular injection of matching placebo (0 mg) was administered weekly for 4 weeks for participants with focal cartilage lesions of the knee.
AEs in long term Follow-Up (FU) period are reported form Day 51 to Day 365.
0
15
0
15
1
15
EG007
LNA043 20 mg Part B - FU
Part B: a single intra-articular injection of 20 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
AEs in long term Follow-Up (FU) period are reported form Day 114 to Day 365.
0
27
1
27
3
27
EG008
LNA043 40 mg Part B - FU
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
AEs in long term Follow-Up (FU) period are reported form Day 114 to Day 365.
0
27
0
27
5
27
EG009
Placebo Part B - FU
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
AEs in long term Follow-Up (FU) period are reported form Day 114 to Day 365.
0
29
2
29
12
29
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Blood loss anaemia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG0030 affected27 at risk
EG0040 affected29 at risk
EG0050 affected43 at risk
EG0060 affected15 at risk
EG0070 affected27 at risk
EG0080 affected27 at risk
EG0091 affected29 at risk
Odontogenic cyst
Congenital, familial and genetic disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Colitis ischaemic
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Acute myeloid leukaemia
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Vena cava thrombosis
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG0030 affected27 at risk
EG0041 affected29 at risk
EG0050 affected43 at risk
EG0060 affected15 at risk
EG0070 affected27 at risk
EG0080 affected27 at risk
EG0090 affected29 at risk
Anaemia macrocytic
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Homocystinaemia
Congenital, familial and genetic disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Odontogenic cyst
Congenital, familial and genetic disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Thyroid mass
Endocrine disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Cataract
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Gastritis haemorrhagic
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Hiatus hernia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Large intestine polyp
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Inflammation
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Injection site bruising
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Injection site erythema
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Injection site haematoma
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Injection site joint erythema
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Injection site joint pain
General disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Peripheral swelling
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Pyrexia
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Vessel puncture site haemorrhage
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
COVID-19
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Gingivitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Infected dermal cyst
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Bone contusion
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Epicondylitis
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Meniscus cyst
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Nail injury
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Tendon injury
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Tooth fracture
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Traumatic haematoma
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Blood pressure increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Blood uric acid increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Cardiac murmur
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Haematology test abnormal
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Urine protein/creatinine ratio increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0003 affected43 at risk
EG0011 affected15 at risk
EG0021 affected27 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Chondropathy
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Costochondritis
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Foot deformity
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Joint effusion
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0004 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0021 affected27 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Osteopenia
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Seborrhoeic keratosis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Headache
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0006 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Seizure
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Syncope
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Depression
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Microalbuminuria
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Atrophic vulvovaginitis
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Benign prostatic hyperplasia
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Breast pain
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Ovulation pain
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected15 at risk
EG0020 affected27 at risk
EG003
Dermal cyst
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Lichenoid keratosis
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Haematoma
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
Varicose vein
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected15 at risk
EG0020 affected27 at risk
EG003
For several outcomes there was a loss in samples size, which may limit the interpretability of results. For Part B, subgroup 1 was defined to address heterogeneity in MRI quality, and to ensure validity of the reported data. P-values for T2 relaxation time are omitted, as there was an error in the calculation. For Part A, the protocol sample size section refers to a ratio for the primary analysis, but data was reported as superficial and deep cartilage layers separately. Both will be updated.
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.
Part B: a single intra-articular injection of 40 mg LNA043 was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.
OG004
Placebo Part B
Part B: a single intra-articular injection of matching placebo (0 mg) was administered every 4 weeks from Week 1 to Week 13 (4 injections) for participants with osteoarthritis.