Knee Cartilage LesionPhase 2ACINCT03334812

Study on Safety, Tolerability and Prelimenary Efficacy of LNA043 in Patients Undergoing Autologous Chondrocyte Implantation

A Phase 2 study testing LNA043 in people with Knee Cartilage Lesion, run by Novartis Pharmaceuticals at 2 sites in Austria.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 50 years
Conditions the study is for: Knee Cartilage Lesion
What is being tested?: LNA043
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 14 participants
Where: 2 sitesAustria
Study dates: 18 Oct 2017to 5 Apr 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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).

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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.

Trial locations and contacts

2 sites in 1 country.

Austria2 sites

Novartis Investigative Site
Vienna, 1090
Novartis Investigative Site
Vienna, 1180

Other trials in Austria

About this study

Official title: A Randomized, Placebo-controlled, Patient and Investigator Blinded, Single Dose, Proof of Concept Study Investigating the Safety, Tolerability and Preliminary Efficacy of Intra-articular LNA043 in Regenerating the Articular Cartilage of the Knee at Donor Sites in Patients Undergoing Autologous Chondrocyte Implantation

Read the 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

Conditions: Knee Cartilage Lesion
Being tested: LNA043, placebo to LNA043
Keywords: cartilage lesion, ACI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LNA043Biological
LNA043 Single dose
placebo to LNA043Biological
placebo to LNA043 single dose

Study groups in NCT03334812
Study group	Role	What they receive
LNA043 20mg/ml	Experimental	LNA043 20mg/ml single dose Receives: Biological: LNA043
Matching placebo to 20mg	Placebo comparator	Matching placebo to 20mg/3ml, single dose Receives: Biological: placebo to LNA043
LNA043 40mg/ml	Experimental	LNA043 40mg/ml single dose Receives: Biological: LNA043
Matching placebo to 40mg	Placebo comparator	Matching placebo to 40mg/4ml, single dose Receives: Biological: placebo to LNA043

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline, Week 4
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.
Measured: Week 4

Secondary outcomes (7)

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).
Measured: Week 4
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.
Measured: Baseline, Week 4, Week 12 and Week 28
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
Measured: Baseline, Week 12 and Week 28
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.
Measured: Week 12 and Week 28
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Measured: 4 weeks
PK Profile of LNA043 and of AngPTL3 in Serum AUC
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Measured: 4 weeks
Number of Participants With Anti-LNA043 Antibodies in Serum
Potential immunogenicity of LNA043
Measured: Baseline, Week 1, Week 4, Week 12 and Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Oct 20175 Apr 2019

First posted7 Nov 2017
Study start18 Oct 2017
Primary completion5 Apr 2019
Study completion5 Apr 2019

Why it stopped: This study was terminated early based on an interim analysis of 14 subjects, which demonstrated a favorable safety and tolerability profile.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Knee Cartilage LesionStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03334812
Sponsor's protocol ID: CLNA043X2201
Acronym: ACI
Status last verified: Oct 2021
First submitted: 16 Oct 2017
Last updated: 7 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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BioPoly® Partial Resurfacing Knee Implant IDE
Knee Pain Chronic, Knee Osteoarthritis
RecruitingPhase 3
Phase 3 Pivotal Trial Comparing CARTISTEM® and Surgical Comparator for Knee Cartilage Lesions and Osteoarthritis
Knee Cartilage Defects
Active, not recruiting
Episealer® Knee System IDE Clinical Study
Degenerative Lesion of Articular Cartilage of Knee
RecruitingObservational study
Knee Cartilage Repair Registry
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Active, not recruiting
The Hyalex First-in-Human Study
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All Knee Cartilage Lesion trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo-controlled, Patient and Investigator Blinded, Single Dose, Proof of Concept Study Investigating the Safety, Tolerability and Preliminary Efficacy of Intra-articular LNA043 in Regenerating the Articular Cartilage of the Knee at Donor Sites in Patients Undergoing Autologous Chondrocyte Implantation
ClinicalTrials.gov ID: NCT03334812
Acronym / sponsor ID: ACI / CLNA043X2201
Conditions: Knee Cartilage Lesion
Keywords: cartilage lesion, ACI
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: This study was terminated early based on an interim analysis of 14 subjects, which demonstrated a favorable safety and tolerability profile.
Enrolment: 14 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 18 Oct 2017 (actual)
Primary completion: 5 Apr 2019 (actual)
Study completion: 5 Apr 2019 (actual)
First posted: 7 Nov 2017 (actual)
Results: Posted 17 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
LNA043 20mg/ml	Experimental	Biological: LNA043LNA043 20mg/ml single dose
Matching placebo to 20mg	Placebo comparator	Biological: placebo to LNA043Matching placebo to 20mg/3ml, single dose
LNA043 40mg/ml	Experimental	Biological: LNA043LNA043 40mg/ml single dose
Matching placebo to 40mg	Placebo comparator	Biological: placebo to LNA043Matching placebo to 40mg/4ml, single dose

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LNA043LNA043 Single dose	Biological	LNA043 20mg/ml, LNA043 40mg/ml
placebo to LNA043placebo to LNA043 single dose	Biological	Matching placebo to 20mg, Matching placebo to 40mg

Primary outcome

Change From Baseline in GAG Content
Time frame: 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
Time frame: 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.

7 secondary outcomes

Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Time frame: Week 4
Percentage of Donor Site Refilling Based on MRI Measurements.
Time frame: Baseline, Week 4, Week 12 and Week 28
Change From Baseline in GAG Content
Time frame: Baseline, Week 12 and Week 28
Bi-layer Collagen Organization Based on MRI Measurements
Time frame: Week 12 and Week 28
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
Time frame: 4 weeks
PK Profile of LNA043 and of AngPTL3 in Serum AUC
Time frame: 4 weeks
Number of Participants With Anti-LNA043 Antibodies in Serum
Time frame: Baseline, Week 1, Week 4, Week 12 and Week 28

Results and safety

Results posted to the registry on 17 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LNA043 20mg	9	9
Matching Placebo to 20mg	5	5
LNA043 40mg	0	0
Matching Placebo to 40mg	0	0

Primary outcome: Change From Baseline in GAG Content

Time frame: Baseline, Week 4. Least squares mean (Standard Error). Unit: Ratio

Measure	LNA043 20mg n = 7	Matching Placebo to 20mg n = 2
SCD/HNWB	0.24 (0.06)	0.06 (0.12)
DTBT/HWB	0.08 (0.04)	0.09 (0.09)

LNA043 20mg vs Matching Placebo to 20mg: Mean Difference (Net): 0.18 (95% CI -0.15 to 0.51), p = 0.1219, Mixed Effect Model Repeat Measurement
LNA043 20mg vs Matching Placebo to 20mg: Mean Difference (Net): -0.01 (95% CI -0.28 to 0.25), p = 0.5438, Mixed Effect Model Repeat Measurement

Population analysed: 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.

Primary outcome: Bi-layer Collagen Organization Based on MRI Measurements

Time frame: Week 4. Mean (Standard Error). Unit: Ratio

Measure	LNA043 20mg n = 7	Matching Placebo to 20mg n = 4
Value	1.01 (0.07)	0.95 (0.09)

LNA043 20mg vs Matching Placebo to 20mg: Mean Difference (Final Values): 0.06 (95% CI -0.19 to 0.31), p = 0.3067, Mixed Effect Model Repeat Measurement

Population analysed: 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.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the dose of study treatment until up to 28 weeks post treatment. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LNA043 20mg	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9
Placebo	0 of 5 (0%)	4 of 5 (80%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
Individual participant dataSharing planned: 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

Related trials for Knee Cartilage Lesion

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Phase 3 Pivotal Trial Comparing CARTISTEM® and Surgical Comparator for Knee Cartilage Lesions and Osteoarthritis
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The Hyalex First-in-Human Study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LNA043 in people with Knee Cartilage Lesion, run by Novartis Pharmaceuticals at 2 sites in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in GAG Content (time frame: Baseline, Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03334812.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.