Knee Cartilage Lesion
Conditions
Keywords
cartilage lesion, ACI
Brief summary
The purpose of this study was to assess safety, tolerability, pharmacokinetics and preliminary efficacy of a single intra-articular (i.a.) administration of LNA043 in regenerating the articular cartilage of the knee, in a standardized clinical scenario of acute cartilage defect. The study aimed at characterizing the mechanism of action of LNA043
Detailed description
This was a non-confirmatory, patient and investigator blinded, randomized, placebo-controlled, parallel group, single dose study in patients with cartilage lesions undergoing autologous cartilage implantation (ACI). Participants were treated only on one occasion (Day 1) with a single i.a. injection that was performed under arthroscopic visualization and followed up for 28 weeks. Originally approximately 22 patients were planned to be enrolled in two cohorts (LNA043 20 mg and LNA043 40 mg). The study was terminated before any patient was randomized into the LNA043 40 mg cohort
Interventions
BIOLOGICALLNA043
LNA043 Single dose
BIOLOGICALplacebo to LNA043
placebo to LNA043 single dose
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed * Patient is ≥18 and≤ 50 years old at time of screening * Patient has a body mass index (BMI) \<30 kg/m2 at screening * Patient has a localized articular cartilage defect of the knee and is scheduled for an ACI procedure * Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Exclusion criteria
* Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2 based on X-ray evaluation performed within 6 months from screening * Patient has unstable knee joint or insufficiently reconstructed ligaments, based on medical history and physical examination by the investigator. * Patient scheduled for a concomitant articular surgical procedure (e.g., anterior cruciate ligament reconstruction) other than debridement or partial meniscectomy * Patient has malalignment (valgus- or varus-deformity) in the target knee ≥ 5° based on based on X-ray evaluation performed within 6 months from screening.at screeningmedical history. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior projection. * Patient has a known autoimmune disease, inflammatory arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, CPPD, gout), active acute or chronic infection of the joint, recent Lyme disease to the knee, systemic cartilage disorder, or a known systemic connective tissue disease. * Patient has had surgical treatment of the target knee using autologous osteochondral transplantation/mosaicplasty within 12 months prior to screening (Note: prior diagnostic arthroscopy with debridement and lavage, meniscal surgery, microfracture, anterior cruciate ligament reconstruction, and extra-articular surgery e.g., high-tibial osteotomy are acceptable). * Patient is unable to undergo magnetic resonance imaging (MRI) or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator). * Patient taking medications prohibited by the protocol: corticosteroids by any route (except topical) from 4 weeks prior to screening; nonsteroidal anti-inflammatories or aspirin (greater than 100 mg per day) within 2 weeks prior to screening; paracetamol greater than 3000 mg per day within 2 weeks prior to screening; glucosamine or chondroitin sulfate within 2 weeks prior to screening; any local treatment i.a. into the knee within 3 months from screening. * 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. * Regular smokers (use of tobacco/nicotine products in the previous 3 months \> 5 cigarettes/day). Urine cotinine levels will be measured during screening for all subjects. Regular smokers will be defined as any subject who reports tobacco use of \> 5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in GAG Content | Baseline, Week 4 | Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content were assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB and the defect to be treated (DTBT or main lesion) to healthy weight bearing region (HWB), i.e. DTBT/HWB was of major interest |
| Bi-layer Collagen Organization Based on MRI Measurements | Week 4 | MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the surgically created defect (SCD) and defect to be treated (DTBT) cartilage regions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Week 4 | Extent of the repair tissue at the donor site before surgery. Each criterion was evaluated based on the visual analog scale and graded from 0 (best) to 100 (worst). |
| Percentage of Donor Site Refilling Based on MRI Measurements. | Baseline, Week 4, Week 12 and Week 28 | Extent of filling of the donor site over a longer term. Percentage change from baseline in refilling of cartilage defect based on 7T MRI for donor Region. |
| PK Profile of LNA043 and of AngPTL3 in Serum AUC | 4 weeks | Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration |
| Change From Baseline in GAG Content | Baseline, Week 12 and Week 28 | Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content was assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB was of major interest |
| Bi-layer Collagen Organization Based on MRI Measurements | Week 12 and Week 28 | MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the SCD cartilage region. |
| Number of Participants With Anti-LNA043 Antibodies in Serum | Baseline, Week 1, Week 4, Week 12 and Week 28 | Potential immunogenicity of LNA043 |
| PK Profile of LNA043 and of AngPTL3 in Serum Cmax | 4 weeks | Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration |
Countries
Austria
Participant flow
Recruitment details
All patients were recruited from 3 clinical sites in Austria.
Pre-assignment details
The original set up of this trial was for 2 cohorts of LNA043 (20 mg and 40 mg). The trial was terminated before any patient in the LNA043 40 mg cohort was randomized
Participants by arm
| Arm | Count |
|---|---|
| LNA043 20mg LNA043 20mg/3ml single dose | 9 |
| Matching Placebo to 20mg Matching placebo to 20mg/3ml, single dose | 5 |
| Total | 14 |
Baseline characteristics
| Characteristic | LNA043 20mg | Matching Placebo to 20mg | Total |
|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 6.16 | 39.4 years STANDARD_DEVIATION 7.4 | 34.0 years STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized White | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 0 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 |
| other Total, other adverse events | 4 / 9 | 4 / 5 |
| serious Total, serious adverse events | 0 / 9 | 0 / 5 |
Outcome results
Primary
Bi-layer Collagen Organization Based on MRI Measurements
MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the surgically created defect (SCD) and defect to be treated (DTBT) cartilage regions.
Time frame: Week 4
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNA043 20mg | Bi-layer Collagen Organization Based on MRI Measurements | 1.01 Ratio | Standard Error 0.07 |
| Matching Placebo to 20mg | Bi-layer Collagen Organization Based on MRI Measurements | 0.95 Ratio | Standard Error 0.09 |
p-value: 0.306795% CI: [-0.19, 0.31]Mixed Effect Model Repeat Measurement
Primary
Change From Baseline in GAG Content
Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content were assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB and the defect to be treated (DTBT or main lesion) to healthy weight bearing region (HWB), i.e. DTBT/HWB was of major interest
Time frame: Baseline, Week 4
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | Change From Baseline in GAG Content | SCD/HNWB | 0.24 Ratio | Standard Error 0.06 |
| LNA043 20mg | Change From Baseline in GAG Content | DTBT/HWB | 0.08 Ratio | Standard Error 0.04 |
| Matching Placebo to 20mg | Change From Baseline in GAG Content | SCD/HNWB | 0.06 Ratio | Standard Error 0.12 |
| Matching Placebo to 20mg | Change From Baseline in GAG Content | DTBT/HWB | 0.09 Ratio | Standard Error 0.09 |
Comparison: SCD/HNWBp-value: 0.121995% CI: [-0.15, 0.51]Mixed Effect Model Repeat Measurement
Comparison: DTBT/HWBp-value: 0.543895% CI: [-0.28, 0.25]Mixed Effect Model Repeat Measurement
Secondary
Bi-layer Collagen Organization Based on MRI Measurements
MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the SCD cartilage region.
Time frame: Week 12 and Week 28
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | Bi-layer Collagen Organization Based on MRI Measurements | Week 12 | 1.44 Ratio | Standard Error 0.15 |
| LNA043 20mg | Bi-layer Collagen Organization Based on MRI Measurements | Week 28 | 1.33 Ratio | Standard Error 0.11 |
| Matching Placebo to 20mg | Bi-layer Collagen Organization Based on MRI Measurements | Week 12 | 1.57 Ratio | Standard Error 0.18 |
| Matching Placebo to 20mg | Bi-layer Collagen Organization Based on MRI Measurements | Week 28 | 1.45 Ratio | Standard Error 0.14 |
Secondary
Change From Baseline in GAG Content
Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content was assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB was of major interest
Time frame: Baseline, Week 12 and Week 28
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | Change From Baseline in GAG Content | SCD/HNWB - Week 12 | 0.14 Ratio | Standard Error 0.07 |
| LNA043 20mg | Change From Baseline in GAG Content | SCD/HNWB - Week 28 | 0.33 Ratio | Standard Error 0.1 |
| Matching Placebo to 20mg | Change From Baseline in GAG Content | SCD/HNWB - Week 12 | 0.15 Ratio | Standard Error 0.09 |
| Matching Placebo to 20mg | Change From Baseline in GAG Content | SCD/HNWB - Week 28 | 0.14 Ratio | Standard Error 0.14 |
Comparison: SCD/HNWB - Week 12p-value: 0.517595% CI: [-0.26, 0.25]Mixed Effect Model Repeat Measurement
Comparison: SCD/HNWB - Week 28p-value: 0.147695% CI: [-0.22, 0.6]Mixed Effect Model Repeat Measurement
Secondary
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Extent of the repair tissue at the donor site before surgery. Each criterion was evaluated based on the visual analog scale and graded from 0 (best) to 100 (worst).
Time frame: Week 4
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Abnormal Calcification/Ossification | 98.75 Unit on a scale | Standard Error 1.05 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Cell Morphology | 61.43 Unit on a scale | Standard Error 14.14 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Chondrocyte clustering | 85.71 Unit on a scale | Standard Error 8.37 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Inflammation | 92.50 Unit on a scale | Standard Error 2.15 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Matrix Staining | 57.14 Unit on a scale | Standard Error 12.17 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Overall assessment | 49.29 Unit on a scale | Standard Error 12.23 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Tissue Morphology | 71.43 Unit on a scale | Standard Error 7.78 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Vascularisation in repaired tissue | 66.25 Unit on a scale | Standard Error 12.88 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Basal Integration | 82.86 Unit on a scale | Standard Error 10.64 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Formation of a Tidemark | 65.71 Unit on a scale | Standard Error 18.15 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Mid/Deep zone assessment | 50.00 Unit on a scale | Standard Error 14.56 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Subcondral bone abnormalities/marrow fibrosis | 73.75 Unit on a scale | Standard Error 13.45 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Surface Architecture | 57.86 Unit on a scale | Standard Error 11.33 |
| LNA043 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Surface/Superficial assessment | 56.43 Unit on a scale | Standard Error 11.42 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Mid/Deep zone assessment | 56.67 Unit on a scale | Standard Error 22.24 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Abnormal Calcification/Ossification | 100.00 Unit on a scale | Standard Error 1.48 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Vascularisation in repaired tissue | 77.50 Unit on a scale | Standard Error 18.21 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Cell Morphology | 56.67 Unit on a scale | Standard Error 21.6 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Surface Architecture | 80.00 Unit on a scale | Standard Error 17.31 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Chondrocyte clustering | 85.00 Unit on a scale | Standard Error 12.78 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Basal Integration | 90.00 Unit on a scale | Standard Error 16.26 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Inflammation | 98.75 Unit on a scale | Standard Error 3.04 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Subcondral bone abnormalities/marrow fibrosis | 77.50 Unit on a scale | Standard Error 19.01 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Matrix Staining | 25.00 Unit on a scale | Standard Error 18.59 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Formation of a Tidemark | 63.33 Unit on a scale | Standard Error 27.72 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Overall assessment | 55.00 Unit on a scale | Standard Error 18.68 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Surface/Superficial assessment | 83.33 Unit on a scale | Standard Error 17.44 |
| Matching Placebo to 20mg | Change From Baseline in International Cartilage Repair Society (ICRS) Scoring | Tissue Morphology | 65.00 Unit on a scale | Standard Error 11.88 |
Secondary
Number of Participants With Anti-LNA043 Antibodies in Serum
Potential immunogenicity of LNA043
Time frame: Baseline, Week 1, Week 4, Week 12 and Week 28
Population: Safety Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 1: anti-LNA043 antibodies present | YES | 0 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 1: anti-LNA043 antibodies present | NO | 9 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 8: anti-LNA043 antibodies present | YES | 0 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 8: anti-LNA043 antibodies present | NO | 9 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 29: anti-LNA043 antibodies present | YES | 0 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 29: anti-LNA043 antibodies present | NO | 9 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 85: anti-LNA043 antibodies present | YES | 0 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 85: anti-LNA043 antibodies present | NO | 9 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 197: anti-LNA043 antibodies present | YES | 0 Participants |
| LNA043 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 197: anti-LNA043 antibodies present | NO | 9 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 85: anti-LNA043 antibodies present | NO | 5 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 1: anti-LNA043 antibodies present | YES | 0 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 29: anti-LNA043 antibodies present | NO | 5 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 1: anti-LNA043 antibodies present | NO | 5 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 197: anti-LNA043 antibodies present | NO | 5 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 8: anti-LNA043 antibodies present | YES | 0 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 85: anti-LNA043 antibodies present | YES | 0 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 8: anti-LNA043 antibodies present | NO | 5 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 197: anti-LNA043 antibodies present | YES | 0 Participants |
| Matching Placebo to 20mg | Number of Participants With Anti-LNA043 Antibodies in Serum | Day 29: anti-LNA043 antibodies present | YES | 0 Participants |
Secondary
Percentage of Donor Site Refilling Based on MRI Measurements.
Extent of filling of the donor site over a longer term. Percentage change from baseline in refilling of cartilage defect based on 7T MRI for donor Region.
Time frame: Baseline, Week 4, Week 12 and Week 28
Population: Pharmacodynamic analysis set. Subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 4 | 64.38 Percent | Standard Error 7.8 |
| LNA043 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 12 | 60.25 Percent | Standard Error 14.55 |
| LNA043 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 28 (EOS) | 86.53 Percent | Standard Error 11.09 |
| Matching Placebo to 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 4 | 38.15 Percent | Standard Error 11.03 |
| Matching Placebo to 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 12 | 32.44 Percent | Standard Error 19.09 |
| Matching Placebo to 20mg | Percentage of Donor Site Refilling Based on MRI Measurements. | Week 28 (EOS) | 62.73 Percent | Standard Error 14.52 |
Comparison: Week 4p-value: 0.040495% CI: [-3.86, 56.32]Mixed Effect Model Repeat Measurement
Comparison: Week 12p-value: 0.138195% CI: [-26.5, 82.1]Mixed Effect Model Repeat Measurement
Comparison: Week 28 (EOS)p-value: 0.116896% CI: [-19.3, 66.89]Mixed Models Analysis
Secondary
PK Profile of LNA043 and of AngPTL3 in Serum AUC
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Time frame: 4 weeks
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | PK Profile of LNA043 and of AngPTL3 in Serum AUC | LNA043 | 821 hr*ng/mL | Standard Deviation 349 |
| LNA043 20mg | PK Profile of LNA043 and of AngPTL3 in Serum AUC | AngPTL3 | 3130 hr*ng/mL | Standard Deviation 1440 |
| Matching Placebo to 20mg | PK Profile of LNA043 and of AngPTL3 in Serum AUC | AngPTL3 | 3030 hr*ng/mL | Standard Deviation 1060 |
Secondary
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Time frame: 4 weeks
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNA043 20mg | PK Profile of LNA043 and of AngPTL3 in Serum Cmax | LNA043 | 57.4 ng/mL | Standard Deviation 22.1 |
| LNA043 20mg | PK Profile of LNA043 and of AngPTL3 in Serum Cmax | AngPTL3 | 22.9 ng/mL | Standard Deviation 9.03 |
| Matching Placebo to 20mg | PK Profile of LNA043 and of AngPTL3 in Serum Cmax | AngPTL3 | 26.6 ng/mL | Standard Deviation 7.62 |