CClinicalTrials.gg
Sign In
CompletedNCT03275064Updated Apr 21, 2026Results posted

Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis.

A Phase 2 interventional study of LNA043 and Placebo in Osteoarthritis, sponsored by Novartis Pharmaceuticals. Completed at 19 sites in 3 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-04-21.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
142
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Osteoarthritis

Browse trials for

Keywords

  • Articular cartilage
  • partial thickness cartilage lesion
  • knee cartilage
  • regeneration
  • osteoarthritis
  • adult
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
142 participants (actual)

Study arms

  • Experimental
    LNA043 40 mg Part B

    LNA043 40 mg Part B

    Biological: LNA043

  • Experimental
    LNA043 20 mg Part B

    LNA043 20 mg Part B

    Biological: LNA043

  • Experimental
    LNA043 20 mg Part A

    LNA043 20 mg Part A

    Biological: LNA043

  • Placebo comparator
    Placebo Part A

    Placebo Part A

    Other: Placebo

  • Placebo comparator
    Placebo Part B

    Placebo Part B

    Other: Placebo

Interventions

  • BiologicalLNA043

    LNA043 intra-articular injection

  • OtherPlacebo

    Placebo intra-articular injection

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline up to Week 16, Week 28

  2. 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.

    Time frame: Baseline up to Week 16, Week 28

  3. 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.

    Time frame: Baseline up to Week 16, Week 28

  4. 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

    Time frame: Baseline, Week 29, Week 53

  5. 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.

    Time frame: Baseline, Week 29, Week 53

  6. 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

    Time frame: Baseline up to end of post treatment follow-up

Secondary outcomes

  1. 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.

    Time frame: Baseline up to Week 16, Week 28

  2. 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.

    Time frame: Baseline, Week 29, Week 53

  3. 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.

    Time frame: Baseline, Week 29, Week 53

  4. 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.

    Time frame: Baseline, Week 29, Week 53

  5. 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.

    Time frame: Week 1,3,8,16,28

  6. 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.

    Time frame: Week 1,5,9,13,17,29,53

  7. 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"

    Time frame: Week 1: 0 (pre-dose), 0.25 hours, 1, 2 hours post dose; Weeks 2, 3, 4: 0 hour (pre dose), 1 hour post dose

  8. 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"

    Time frame: Week 1: 0 (pre-dose), 0.25 hours, 1, 2 hours post dose; Weeks 2, 3, 4: 0 hour (pre dose), 1 hour post dose

  9. 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".

    Time frame: Weeks 1,2,3,4: 0 hour (pre-dose)

  10. 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".

    Time frame: Weeks 1,2,3,4: 0 hour (pre-dose)

  11. 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

    Time frame: Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose

  12. 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".

    Time frame: Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose

  13. 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".

    Time frame: Weeks 1,5.9.13: 0 hour (pre-dose)

  14. 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".

    Time frame: Weeks 1,5.9.13: 0 hour (pre-dose)

06

Results

Posted Feb 14, 2024
Limitations and caveats
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.

Participant flow

Treatment Period Part A and Part B
Participant flow — Treatment Period Part A and Part B
MilestoneLNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Started4315272729
Patient d/c treatment but continued into follow up10000
Completed4315272629
Not completed00010
Withdrew: Pi decision based on poor veins for blood sampling00010
Post-treatment Follow-up Parts A and B
Participant flow — Post-treatment Follow-up Parts A and B
MilestoneLNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Started4315272629
Completed4215242528
Not completed10311
Withdrew: Lost to follow-up00201
Withdrew: No longer required treatment00010
Withdrew: Subject/guardian decision10100

Outcome measures

PrimaryChange 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.

Time frame:
Baseline up to Week 16, Week 28
Reported as:
Mean · ms
Change From Baseline in Articular Cartilage Collagen Organization in the Overall Cartilage (Femoral and Patellar Lesions) - Part A
msLNA043 20 mg Part APlacebo Part A
Week 163.02 ± 9.662.86 ± 16.31
Week 285.59 ± 9.862.05 ± 15.91
Statistical analysis
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (net): 0.48 · 90% CI -30.73 to 31.69
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (net): 3.68 · 90% CI -27.04 to 34.40
PrimaryChange 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.

Time frame:
Baseline up to Week 16, Week 28
Reported as:
Mean · ms
Change From Baseline in Articular Cartilage Collagen Organization in the Deep Cartilage Layer (Femoral and Patellar Lesions) - Part A
msLNA043 20 mg Part APlacebo Part A
Week 16-0.2 ± 8.18-2.20 ± 12.78
Week 284.27 ± 8.68-3.17 ± 11.46
Statistical analysis
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (final values): 1.69 · 90% CI -27.70 to 31.08
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (net): 5.97 · 90% CI -23.03 to 34.97
PrimaryChange 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.

Time frame:
Baseline up to Week 16, Week 28
Reported as:
Mean · ms
Change From Baseline in Articular Cartilage Collagen Organization in the Superficial Cartilage Layer (Femoral and Patellar Lesions) - Part A
msLNA043 20 mg Part APlacebo Part A
Week 16 n=17,7-13.05 ± 15.68-13.93 ± 24.73
Week 28 n=16,9-10.45 ± 16.61-12.73 ± 22.09
Statistical analysis
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (net): 0.88 · 90% CI -47.27 to 49.04
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · Mean difference (net): 2.27 · 90% CI -43.11 to 47.65
PrimaryChange 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

Time frame:
Baseline, Week 29, Week 53
Reported as:
Mean · mm^3
Change From Baseline of LNA043 to Placebo in Cartilage Volume in the Femoral Medial Index Region (mm3) - Part B
mm^3LNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 29 n=12,13,1345.52 ± 61.90-12.79 ± 60.38-154.7 ± 60.25
Week 53 n=11,13,775.54 ± 54.48-36.52 ± 51.21-152.7 ± 67.72
Statistical analysis
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0131 · Mean difference (net): 200.18 · 90% CI 54.53 to 345.83
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0544 · Mean difference (net): 141.87 · 90% CI -3.83 to 287.56
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0067 · Mean difference (net): 228.27 · 90% CI 80.87 to 375.67
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0931 · Mean difference (net): 116.21 · 90% CI -29.52 to 261.94
PrimaryChange 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.

Time frame:
Baseline, Week 29, Week 53
Reported as:
Mean · mm
Change From Baseline of LNA043 to Placebo in Cartilage Thickness in the Femoral Medial Index Region (mm) - Part B
mmLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 29 n=12,13,130.01 ± 0.020.02 ± 0.02-0.04 ± 0.02
Week 53 n=11,13,7-0.01 ± 0.02-0.00 ± 0.02-0.02 ± 0.03
Statistical analysis
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0574 · Mean difference (net): 0.05 · 90% CI -0.00 to 0.10
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.0248 · Mean difference (net): 0.06 · 90% CI 0.01 to 0.11
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.3864 · Mean difference (net): 0.01 · 90% CI -0.05 to 0.07
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · p = 0.3290 · Mean difference (net): 0.02 · 90% CI -0.05 to 0.08
SecondaryChange 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.

Time frame:
Baseline up to Week 16, Week 28
Reported as:
Mean · mm^3
Change From Baseline of LNA043 to Placebo in Cartilage Defect Volume (mm^3) for Both Groups of Patients (Femoral and Patellar Lesions) - Part A
mm^3LNA043 20 mg Part APlacebo Part A
Week 16-2.55 ± 8.15-7.16 ± 13.55
Week 28-11.97 ± 8.19-4.57 ± 13.36
Statistical analysis
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · p = 0.6184 · Mean difference (net): 4.75 · 90% CI -21.36 to 30.85
  • LNA043 20 mg Part A vs Placebo Part A · Mixed Models Analysis · p = 0.3194 · Mean difference (net): -7.32 · 90% CI -33.16 to 18.53
SecondaryChange 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.

Time frame:
Baseline, Week 29, Week 53
Reported as:
Mean · ms
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Overall Part B
msLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 29 n=21,21,25-1.59 ± 2.25-5.07 ± 2.26-4.97 ± 2.07
Week 53 n=20,22,22-4.23 ± 2.29-10.53 ± 2.25-3.09 ± 2.18
Statistical analysis
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): 3.38 · 90% CI -1.72 to 8.47
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -0.10 · 90% CI -5.22 to 5.01
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -1.14 · 90% CI -6.42 to 4.15
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -7.44 · 90% CI -12.68 to -2.20
SecondaryChange 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.

Time frame:
Baseline, Week 29, Week 53
Reported as:
Mean · ms
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Deep Part B
msLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 29 n=21,21,25-3.80 ± 2.47-5.07 ± 2.49-5.89 ± 2.26
Week 53 n=20,22,22-3.93 ± 2.53-12.17 ± 2.54-6.21 ± 2.41
Statistical analysis
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): 2.09 · 90% CI -3.49 to 7.66
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): 0.82 · 90% CI -4.82 to 6.45
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): 2.29 · 90% CI -3.54 to 8.11
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -5.96 · 90% CI -11.81 to -0.10
SecondaryChange 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.

Time frame:
Baseline, Week 29, Week 53
Reported as:
Mean · ms
Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Superficial Part B
msLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 29 n=21,21,25-0.06 ± 2.51-4.16 ± 2.51-3.53 ± 2.30
Week 53 n=20,22,22-3.54 ± 2.36-9.07 ± 2.36-0.91 ± 2.25
Statistical analysis
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): 3.47 · 90% CI -2.21 to 9.15
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -0.63 · 90% CI -6.31 to 5.04
  • LNA043 20 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -2.63 · 90% CI -8.07 to 2.82
  • LNA043 40 mg Part B vs Placebo Part B · Mixed Models Analysis · Mean difference (net): -8.16 · 90% CI -13.61 to -2.72
SecondaryIncidence 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.

Time frame:
Week 1,3,8,16,28
Reported as:
Number · participants
Incidence of Immunogenicity (IG) Part A
participantsLNA043 20 mg Part APlacebo Part A
Week 1 (Day 1) Predose00
Week 3 (Day 15) Pre-dose00
Week 8 (Day 50)00
Week 16 (Day 106)00
Week 28 (Day 190)00
SecondaryIncidence 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.

Time frame:
Week 1,5,9,13,17,29,53
Reported as:
Number · participants
Incidence of Immunogenicity (IG) Part B
participantsLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 1 (Day 1) Predose000
Week 5 Pre-dose000
Week 9000
Week 13000
Week 17000
Week 29000
Week 53000
SecondarySerum 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"

Time frame:
Week 1: 0 (pre-dose), 0.25 hours, 1, 2 hours post dose; Weeks 2, 3, 4: 0 hour (pre dose), 1 hour post dose
Reported as:
Mean · ng/mL
Serum Concentrations of LNA043 - Part A
ng/mLLNA043 20 mg Part A
Week 1, 0 hour pre-dose0 ± 0
Week 1, 0.25 hour post dose n=624.9 ± 16.3
Week 1, 1 hour post dose n=765.1 ± 30.2
Week 1, 2 hours post dose n=4164.9 ± 37.5
Week 2,0 hour pre dose n=420.00 ± 0.00
Week 2, 1 hour post dose n=4348.1 ± 32.9
Week 3, 0 hour pre dose n=410.00 ± 0.00
Week 3, 1 hour post dose n=3951.0 ± 37.6
Week 4, 0 hour pre dose n=423.00 ± 19.4
Week 4, 1 hour post dose n=4152.9 ± 38.1
SecondarySerum 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"

Time frame:
Week 1: 0 (pre-dose), 0.25 hours, 1, 2 hours post dose; Weeks 2, 3, 4: 0 hour (pre dose), 1 hour post dose
Reported as:
Mean · ng/mL
Serum Concentrations of ANGPTL3 - Part A
ng/mLLNA043 20 mg Part APlacebo Part A
Week 1, 0 hour pre-dose n=41,1419.1 ± 9.2923.3 ± 8.55
Week 1, 0.25 hour post dose n=6,220.8 ± 8.1220.4 ± 6.36
Week 1, 1 hour post dose n=7,219.7 ± 8.6518.2 ± 3.32
Week 1, 2 hours post dose n=40,1518.9 ± 9.3824.3 ± 9.52
Week 2,0 hour pre dose n=42,1518.9 ± 10.321.7 ± 10.2
Week 2, 1 hour post dose n=42,1518.3 ± 8.0619.7 ± 9.58
Week 3, 0 hour pre dose n=42,1419.1 ± 7.7924.2 ± 9.95
Week 3, 1 hour post dose n=39,1418.5 ± 7.3528.9 ± 16.4
Week 4, 0 hour pre dose n=42,1519.6 ± 8.7121.0 ± 7.11
Week 4, 1 hour post dose n=41,1519.6 ± 7.8722.6 ± 9.06
SecondarySynovial 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".

Time frame:
Weeks 1,2,3,4: 0 hour (pre-dose)

No measurements were reported for this outcome.

SecondarySynovial 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".

Time frame:
Weeks 1,2,3,4: 0 hour (pre-dose)
Reported as:
Mean · ng/mL
Synovial Fluid Concentrations of ANGPTL3 - Part A
ng/mLLNA043 20 mg Part APlacebo Part A
Week 1, 0 hour pre-dose n=8,30.00 ± 0.0000.0 ± 00.0
Week 2,0 hour pre dose n=11,50.00 ± 0.0000.0 ± 00.0
Week 3, 0 hour pre dose n=13,40.616 ± 2.2200.0 ± 00.0
Week 4, 0 hour pre dose n=15,31.42 ± 5.5000.0 ± 00.0
SecondarySerum 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

Time frame:
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
Reported as:
Mean · ng/mL
Serum Concentrations of LNA043 - Part B
ng/mLLNA043 20 mg Part BLNA043 40 mg Part B
Week 1, 0 hours pre-dose n=27,263.48 ± 18.17.96 ± 40.6
Week 1, 2 hours post dose n=24,24,76.4 ± 51.0158 ± 94.0
Week 5, 1 hour post dose n=27,2655.6 ± 47.0101 ± 74.2
Week 13, 1 hour post dose n=27,2559.5 ± 53.0118 ± 78.2
SecondarySerum 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".

Time frame:
Week 1: 0 (pre-dose), 2 hours post dose; Weeks 5 and 13: 1 hour post dose
Reported as:
Mean · ng/mL
Serum Concentrations of ANGPTL3 - Part B
ng/mLLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 1, 0 hour pre-dose n=27,26,2925.3 ± 11.121.9 ± 9.0926.6 ± 14.0
Week 1, 2 hours post dose n=24,24,2626.0 ± 12.823.9 ± 10.627.6 ± 13.1
Week 5, 1 hour post dose n=26,26,2821.8 ± 9.8023.3 ± 9.9726.2 ± 10.8
Week 13, 1 hour post dose n=27,25,2822.9 ± 8.7222.5 ± 8.3924.8 ± 11.8
SecondarySynovial 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".

Time frame:
Weeks 1,5.9.13: 0 hour (pre-dose)
Reported as:
Mean · ng/mL
Synovial Fluid Concentrations of LNA043 Part B
ng/mLLNA043 20 mg Part BLNA043 40 mg Part B
Week 1, 0 hours pre dose n=9,528.9 ± 86.70.00 ± 0.00
Week 5, 0 hours pre dose n=10,5368 ± 116018.1 ± 40.6
Week 9, 0 hours pre-dose n=11,60.00 ± 0.0043600 ± 90900
Week 13, 0 hours pre dose n=8,40.00 ± 0.00199000 ± 398000
SecondarySynovial 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".

Time frame:
Weeks 1,5.9.13: 0 hour (pre-dose)
Reported as:
Mean · ng/mL
Synovial Fluid Concentrations of ANGPTL3 - Part B
ng/mLLNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part B
Week 1, 0 hour pre-dose n=8,3,80.00 ± 0.000.00 ± 0.000.00 ± 0.00
0.00Week 5,,0 hour pre dose n=10,5,121.00 ± 3.164.38 ± 9.791.57 ± 5.43
Week 9,, 0 hour pre dose n=8,4,90.00 ± 0.000.00 ± 0.000.00 ± 0.00
Week 13, 0 hour pre dose n=7,4,80.00 ± 0.001.87 ± 3.740.890 ± 2.52
PrimaryOverview 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

Time frame:
Baseline up to end of post treatment follow-up
Reported as:
Number · participants
Overview of Number of Participants With Adverse Events and Serious Adverse Events for Part A and Part B
participantsLNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40mg Part BPlacebo Part B
Part A TEAE197———
Part A TESAE00———
Part A - Follow-up AE161———
Part A - Follow-up SAE20———
Part B - TEAE——61510
Part B - TESAE——100
Part B - Follow-up AE——3512
Part B - Follow-up SAE——102

Adverse events

Collected over 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. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LNA043 20 mg Part A - TE0/43 (0%)0/43 (0%)19/43 (44.2%)
Placebo Part A - TE0/15 (0%)0/15 (0%)7/15 (46.7%)
LNA043 20 mg Part B - TE0/27 (0%)1/27 (3.7%)6/27 (22.2%)
LNA043 40 mg Part B - TE0/27 (0%)0/27 (0%)15/27 (55.6%)
Placebo Part B - TE0/29 (0%)0/29 (0%)10/29 (34.5%)
LNA043 20 mg Part A - FU0/43 (0%)2/43 (4.7%)16/43 (37.2%)
Placebo Part A - FU0/15 (0%)0/15 (0%)1/15 (6.7%)
LNA043 20 mg Part B - FU0/27 (0%)1/27 (3.7%)3/27 (11.1%)
LNA043 40 mg Part B - FU0/27 (0%)0/27 (0%)5/27 (18.5%)
Placebo Part B - FU0/29 (0%)2/29 (6.9%)12/29 (41.4%)
Most frequent serious events
Most frequent serious events
EventLNA043 20 mg Part A - TEPlacebo Part A - TELNA043 20 mg Part B - TELNA043 40 mg Part B - TEPlacebo Part B - TELNA043 20 mg Part A - FUPlacebo Part A - FULNA043 20 mg Part B - FULNA043 40 mg Part B - FUPlacebo Part B - FU
COVID-19 pneumoniaInfections and infestations0/430/151/270/270/290/430/150/270/270/29
Acute myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/430/150/270/270/290/430/151/270/270/29
Blood loss anaemiaBlood and lymphatic system disorders0/430/150/270/270/290/430/150/270/271/29
Colitis ischaemicGastrointestinal disorders0/430/150/270/270/290/430/150/270/271/29
Deep vein thrombosisVascular disorders0/430/150/270/270/290/430/150/270/271/29
Vena cava thrombosisVascular disorders0/430/150/270/270/290/430/150/270/271/29
Odontogenic cystCongenital, familial and genetic disorders0/430/150/270/270/291/430/150/270/270/29
Back painMusculoskeletal and connective tissue disorders0/430/150/270/270/291/430/150/270/270/29
Most frequent other events
Showing 10 of 109
Most frequent other events
EventLNA043 20 mg Part A - TEPlacebo Part A - TELNA043 20 mg Part B - TELNA043 40 mg Part B - TEPlacebo Part B - TELNA043 20 mg Part A - FUPlacebo Part A - FULNA043 20 mg Part B - FULNA043 40 mg Part B - FUPlacebo Part B - FU
ArthralgiaMusculoskeletal and connective tissue disorders3/431/151/274/271/293/430/150/272/272/29
HeadacheNervous system disorders6/431/150/270/270/290/430/150/270/270/29
Joint swellingMusculoskeletal and connective tissue disorders4/430/151/271/273/290/430/150/270/270/29
Blood uric acid increasedInvestigations0/430/150/270/270/290/430/150/272/270/29
Abdominal painGastrointestinal disorders0/430/150/270/270/290/430/150/271/272/29
HaemorrhoidsGastrointestinal disorders0/430/150/270/270/290/430/150/270/272/29
COVID-19Infections and infestations0/430/150/270/270/290/430/150/270/272/29
Blood creatine phosphokinase increasedInvestigations1/430/151/271/270/290/430/150/271/272/29
Dental cariesGastrointestinal disorders0/431/150/270/270/290/430/150/270/270/29
GastroenteritisInfections and infestations0/431/150/270/270/290/430/150/270/270/29

Baseline characteristics

Age, Customized
Age, Customized(participants)LNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part BTotal
≥18 and ≤55 years Part A only4315———58
≥18 and ≤64 Part B only——18151548
≥65 and ≤76 years - Part B only——9121435
Sex: Female, Male
Sex: Female, Male(Participants)LNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part BTotal
Female21519202186
Male221087855
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)LNA043 20 mg Part APlacebo Part ALNA043 20 mg Part BLNA043 40 mg Part BPlacebo Part BTotal
Asian110013
White4211202624123
American Indian or Alaska Native010001
Black or African0171312
American Unknow010001
Other000011
07

Study locations

19 sites
  • Arizona Research
    Phoenix, Arizona 85053, United States
  • Scott A Hacker MD Medical Group d b a Horizon Clinical Res
    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
08

References and documents

Study documents

  • Study protocol · Dec 22, 2020
  • Statistical analysis plan · Dec 5, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

09

Registry details

Key details

Study ID
NCT03275064
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 7, 2017
Start date
Sep 12, 2017
Primary completion
Sep 6, 2022
Completion
Sep 6, 2022
Results posted
Feb 14, 2024
Last update
Apr 21, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Osteoarthritis→

Other studies from this sponsor

Novartis Pharmaceuticals

Start the discussion