Trial Outcomes & Findings for Study on Safety, Tolerability and Prelimenary Efficacy of LNA043 in Patients Undergoing Autologous Chondrocyte Implantation (NCT NCT03334812)
NCT ID: NCT03334812
Last Updated: 2021-10-07
Results Overview
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
TERMINATED
PHASE2
14 participants
Baseline, Week 4
2021-10-07
Participant Flow
All patients were recruited from 3 clinical sites in Austria.
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
Participant milestones
| Measure |
LNA043 20mg
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
Matching placebo to 20mg/3ml, single dose
|
LNA043 40mg
LNA043 40mg/4ml single dose
|
Matching Placebo to 40mg
Matching placebo to 40mg/4ml, single dose
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
5
|
0
|
0
|
|
Overall Study
COMPLETED
|
9
|
5
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study on Safety, Tolerability and Prelimenary Efficacy of LNA043 in Patients Undergoing Autologous Chondrocyte Implantation
Baseline characteristics by cohort
| Measure |
LNA043 20mg
n=9 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=5 Participants
Matching placebo to 20mg/3ml, single dose
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.0 years
STANDARD_DEVIATION 6.16 • n=99 Participants
|
39.4 years
STANDARD_DEVIATION 7.40 • n=107 Participants
|
34.0 years
STANDARD_DEVIATION 7.60 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
9 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 4Population: 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.
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
Outcome measures
| Measure |
LNA043 20mg
n=7 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=2 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Change From Baseline in GAG Content
SCD/HNWB
|
0.24 Ratio
Standard Error 0.06
|
0.06 Ratio
Standard Error 0.12
|
|
Change From Baseline in GAG Content
DTBT/HWB
|
0.08 Ratio
Standard Error 0.04
|
0.09 Ratio
Standard Error 0.09
|
PRIMARY outcome
Timeframe: Week 4Population: 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.
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.
Outcome measures
| Measure |
LNA043 20mg
n=7 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=4 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Bi-layer Collagen Organization Based on MRI Measurements
|
1.01 Ratio
Standard Error 0.07
|
0.95 Ratio
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Week 4Population: 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.
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).
Outcome measures
| Measure |
LNA043 20mg
n=8 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=4 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Abnormal Calcification/Ossification
|
98.75 Unit on a scale
Standard Error 1.05
|
100.00 Unit on a scale
Standard Error 1.48
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Cell Morphology
|
61.43 Unit on a scale
Standard Error 14.14
|
56.67 Unit on a scale
Standard Error 21.60
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Chondrocyte clustering
|
85.71 Unit on a scale
Standard Error 8.37
|
85.00 Unit on a scale
Standard Error 12.78
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Inflammation
|
92.50 Unit on a scale
Standard Error 2.15
|
98.75 Unit on a scale
Standard Error 3.04
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Matrix Staining
|
57.14 Unit on a scale
Standard Error 12.17
|
25.00 Unit on a scale
Standard Error 18.59
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Overall assessment
|
49.29 Unit on a scale
Standard Error 12.23
|
55.00 Unit on a scale
Standard Error 18.68
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Tissue Morphology
|
71.43 Unit on a scale
Standard Error 7.78
|
65.00 Unit on a scale
Standard Error 11.88
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Vascularisation in repaired tissue
|
66.25 Unit on a scale
Standard Error 12.88
|
77.50 Unit on a scale
Standard Error 18.21
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Basal Integration
|
82.86 Unit on a scale
Standard Error 10.64
|
90.00 Unit on a scale
Standard Error 16.26
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Formation of a Tidemark
|
65.71 Unit on a scale
Standard Error 18.15
|
63.33 Unit on a scale
Standard Error 27.72
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Mid/Deep zone assessment
|
50.00 Unit on a scale
Standard Error 14.56
|
56.67 Unit on a scale
Standard Error 22.24
|
|
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
|
77.50 Unit on a scale
Standard Error 19.01
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Surface Architecture
|
57.86 Unit on a scale
Standard Error 11.33
|
80.00 Unit on a scale
Standard Error 17.31
|
|
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Surface/Superficial assessment
|
56.43 Unit on a scale
Standard Error 11.42
|
83.33 Unit on a scale
Standard Error 17.44
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 12 and Week 28Population: 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.
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.
Outcome measures
| Measure |
LNA043 20mg
n=8 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=4 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Percentage of Donor Site Refilling Based on MRI Measurements.
Week 12
|
60.25 Percent
Standard Error 14.55
|
32.44 Percent
Standard Error 19.09
|
|
Percentage of Donor Site Refilling Based on MRI Measurements.
Week 28 (EOS)
|
86.53 Percent
Standard Error 11.09
|
62.73 Percent
Standard Error 14.52
|
|
Percentage of Donor Site Refilling Based on MRI Measurements.
Week 4
|
64.38 Percent
Standard Error 7.80
|
38.15 Percent
Standard Error 11.03
|
SECONDARY outcome
Timeframe: Baseline, Week 12 and Week 28Population: 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.
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
Outcome measures
| Measure |
LNA043 20mg
n=7 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=4 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Change From Baseline in GAG Content
SCD/HNWB - Week 12
|
0.14 Ratio
Standard Error 0.07
|
0.15 Ratio
Standard Error 0.09
|
|
Change From Baseline in GAG Content
SCD/HNWB - Week 28
|
0.33 Ratio
Standard Error 0.10
|
0.14 Ratio
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Week 12 and Week 28Population: 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.
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.
Outcome measures
| Measure |
LNA043 20mg
n=6 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=4 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Bi-layer Collagen Organization Based on MRI Measurements
Week 12
|
1.44 Ratio
Standard Error 0.15
|
1.57 Ratio
Standard Error 0.18
|
|
Bi-layer Collagen Organization Based on MRI Measurements
Week 28
|
1.33 Ratio
Standard Error 0.11
|
1.45 Ratio
Standard Error 0.14
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Pharmacokinetic Analysis Set
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Outcome measures
| Measure |
LNA043 20mg
n=8 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=5 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
LNA043
|
57.4 ng/mL
Standard Deviation 22.1
|
—
|
|
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
AngPTL3
|
22.9 ng/mL
Standard Deviation 9.03
|
26.6 ng/mL
Standard Deviation 7.62
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Pharmacokinetic Analysis Set
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Outcome measures
| Measure |
LNA043 20mg
n=8 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=5 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
PK Profile of LNA043 and of AngPTL3 in Serum AUC
LNA043
|
821 hr*ng/mL
Standard Deviation 349
|
—
|
|
PK Profile of LNA043 and of AngPTL3 in Serum AUC
AngPTL3
|
3130 hr*ng/mL
Standard Deviation 1440
|
3030 hr*ng/mL
Standard Deviation 1060
|
SECONDARY outcome
Timeframe: Baseline, Week 1, Week 4, Week 12 and Week 28Population: Safety Analysis Set
Potential immunogenicity of LNA043
Outcome measures
| Measure |
LNA043 20mg
n=9 Participants
LNA043 20mg/3ml single dose
|
Matching Placebo to 20mg
n=5 Participants
Matching placebo to 20mg/3ml, single dose
|
|---|---|---|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 8: anti-LNA043 antibodies present · NO
|
9 Participants
|
5 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 29: anti-LNA043 antibodies present · YES
|
0 Participants
|
0 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 1: anti-LNA043 antibodies present · YES
|
0 Participants
|
0 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 1: anti-LNA043 antibodies present · NO
|
9 Participants
|
5 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 8: anti-LNA043 antibodies present · YES
|
0 Participants
|
0 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 29: anti-LNA043 antibodies present · NO
|
9 Participants
|
5 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 85: anti-LNA043 antibodies present · YES
|
0 Participants
|
0 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 85: anti-LNA043 antibodies present · NO
|
9 Participants
|
5 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 197: anti-LNA043 antibodies present · YES
|
0 Participants
|
0 Participants
|
|
Number of Participants With Anti-LNA043 Antibodies in Serum
Day 197: anti-LNA043 antibodies present · NO
|
9 Participants
|
5 Participants
|
Adverse Events
LNA043 20mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LNA043 20mg
n=9 participants at risk
LNA043 20mg
|
Placebo
n=5 participants at risk
Placebo
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Endocrine disorders
Thyroid mass
|
0.00%
0/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
20.0%
1/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
40.0%
2/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
General disorders
Influenza like illness
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
20.0%
1/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
20.0%
1/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Injury, poisoning and procedural complications
Fall
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
0.00%
0/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
20.0%
1/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
0.00%
0/5 • Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER