OsteoarthritisPhase 2ONWARDSNCT04864392
Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis
A Phase 2 study testing LNA043 in people with Osteoarthritis, run by Novartis Pharmaceuticals at 75 sites in 15 countries.
Trial summary
This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- LNA043
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 576 participants
- Where
- 75 sitesin 15 countries
- Study dates
- 31 May 2021to 29 May 2025
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females between 40 and 75 years of age
- Body mass index (BMI) < 40 kg/m2
- Diagnosis of primary tibiofemoral knee OA by standard American College of Rheumatology clinical and radiographic criteria
Who cannot join
- Participants with radiographic knee OA K-L grade = 4 on the non-target knee
- Arthroscopy of the target knee within the 6 months prior to Screening
- Hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/μL
Trial locations and contacts
75 sites in 15 countries.
75 sites in 15 countries
United States23 sites
Charlottesville Medical Research
Charlottesville, Virginia, 22911
Chicago Clinical Research Inst
Chicago, Illinois, 60607
Metroplex Clinical Research
Dallas, Texas, 75231
Annapolis Rheumatology LLC
Fairfax, Virginia, 22033
Drug Trials America
Hartsdale, New York, 10530
Center For Pharmaceutical Research
Kansas City, Missouri, 64114
AMR Knoxville
Knoxville, Tennessee, 37920
Sharps Hospital Grossmont
La Mesa, California, 91942
Clinical Trials Research
Lincoln, California, 95648
Long Beach Clinical Trials
Long Beach, California, 90806
Tandem clinical research
Marrero, Louisiana, 70072
Sensible Healthcare
Ocoee, Florida, 34761
Elite Clinical Studies
Phoenix, Arizona, 85018
Virginia Ispine Physicians PC
Richmond, Virginia, 23238
Artemis Institute Clinical Research
Riverside, California, 92503
Northern California Research
Sacramento, California, 95821
Arthemis Clinical Research
San Diego, California, 92103
Stamford Therapeutics Consortium LLC
Stamford, Connecticut, 06905
Pioneer Research Solutions
Sugar Land, Texas, 77479
Clinical Research of West Florida Inc
Tampa, Florida, 33603
Tucson Orthopedic Institute PC
Tucson, Arizona, 85712
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902
Conquest Research
Winter Park, Florida, 32789
Australia8 sites
Novartis Investigative Site
Broadmeadow, New South Wales, 2292
Novartis Investigative Site
Christchurch, 8011
Novartis Investigative Site
Hobart, Tasmania, 7000
Novartis Investigative Site
Malvern East, Victoria, 3145
Novartis Investigative Site
Maroochydore, Queensland, 4558
Novartis Investigative Site
St Leonards, 2065
Novartis Investigative Site
Waikanae Beach, 5036
Novartis Investigative Site
Woodville South, South Australia, 5011
Spain6 sites
Novartis Investigative Site
A Coruña, 15006
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Sabadell, Barcelona, 08208
Novartis Investigative Site
Santiago, A Coruna, 15705
Novartis Investigative Site
Seville, 41010
Czechia5 sites
Novartis Investigative Site
Brno, Czech Republic, 66250
Novartis Investigative Site
Brno, 638 00
Novartis Investigative Site
Brno-Zidonice, CZE, 61500
Novartis Investigative Site
Pardubice, Czech Republic, 530 02
Novartis Investigative Site
Uherské Hradiště, 686 01
Japan5 sites
Novartis Investigative Site
Chuoh-ku, 104-0031
Novartis Investigative Site
Osaka, 543-0027
Novartis Investigative Site
Shinagawa, Tokyo, 140 0014
Novartis Investigative Site
Shinjuku Ku, Tokyo, 160-0008
Novartis Investigative Site
Suginami, Tokyo, 166-0002
India4 sites
Novartis Investigative Site
Belagavi, Karnataka, 590010
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226003
Novartis Investigative Site
Pune, 411019
Novartis Investigative Site
Vadodara, Gujarat, 390022
Poland4 sites
Novartis Investigative Site
Kielce, 25-017
Novartis Investigative Site
Krakow, 31-501
Novartis Investigative Site
Poznan, 60-446
Novartis Investigative Site
Warsaw, 02-677
Argentina3 sites
Novartis Investigative Site
Caba, C1428AZF
Novartis Investigative Site
Córdoba, X5000EOC
Novartis Investigative Site
San Miguel de Tucumán, 4000
Denmark3 sites
Novartis Investigative Site
Aarhus N, 8200
Novartis Investigative Site
Gandrup, 9362
Novartis Investigative Site
Vejle, 7100
Mexico3 sites
Novartis Investigative Site
Ciudad de, CP 06700
Novartis Investigative Site
Culiacán, Sinaloa, 80000
Novartis Investigative Site
Guadalajara, Jalisco, 44650
United Kingdom3 sites
Novartis Investigative Site
Barnet, EN5 3DJ
Novartis Investigative Site
Glasgow, Scotland, G51 4TF
Novartis Investigative Site
Norwich, NR4 7UY
Canada2 sites
Novartis Investigative Site
Québec, Quebec, G1V 3M7
Novartis Investigative Site
Trois-Rivières, Quebec, G9A 3Y2
China2 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100044
Novartis Investigative Site
Bengbu, 233004
Estonia2 sites
Novartis Investigative Site
Tallinn, 10128
Novartis Investigative Site
Tartu, 50708
Taiwan2 sites
Novartis Investigative Site
Changhua, 50006
Novartis Investigative Site
Tainan, 704302
About this study
Official title: A 5-year, Randomized, Double-blind, Placebo-controlled, Multi-center Study Assessing the Efficacy, Safety, and Tolerability of Intra-articular Regimens of LNA043 Versus Placebo in Patients With Symptomatic Knee Osteoarthritis
This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis.
Read the detailed description
The study was structured as a two-period design:
- A 2-year Core Period, followed by
- A 3-year Extension Period, consisting of 2 years of continued treatment and 1 year of follow-up, totaling 5 years.
Participants were randomized in a 1:1:1:1:1 ratio into five treatment arms:
- LNA043 20 mg Q4w ×3, repeated every 6 months.
- LNA043 40 mg ×1 and placebo Q4w ×2, repeated every 6 months.
- LNA043 40 mg Q4w ×3 followed six months later by placebo Q4w ×3, repeated every 12 months.
- LNA043 40 mg Q4w ×3, repeated every 6 months.
- Placebo Q4w ×3, repeated every 6 months.
All injections were administered intra-articularly (i.a.) to the target knee. Placebo injections (saline solution) were used throughout the study to maintain blinding and ensure consistency in injection frequency across arms.
During the Extension Period:
- Participants from the 6-month cycle arms continued with a single injection of the same LNA043 dose every 6 months.
- Participants from the 12-month cycle arm received LNA043 40 mg every 12 months and placebo every other 6 months.
- Participants who received placebo during the Core Period continued with a single injection of the same placebo every 6 months.
The final year of the Extension Period was a no-treatment follow-up phase for all participants.
The study was terminated early following the Week 104 primary endpoint analysis due to lack of effect.There was no safety related reasons for early termination or safety concerns for the subjects in the study.
- Conditions
- Osteoarthritis
- Being tested
- LNA043, Placebo
- Keywords
- LNA043, knee, arthritis, OA, knees
- Medical subject headings
- Osteoarthritis, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNA043Drug
LNA043 was administered intra-articularly in various dosing regimens across four active treatment arms:
- Arm 1: LNA043 40 mg Q4W ×3, repeated every 6 months
- Arm 2: LNA043 40 mg Q4W ×3, followed six months later by placebo Q4W ×3, repeated every 12 months
- Arm 3: LNA043 20 mg Q4W ×3, repeated every 6 months
- Arm 4: LNA043 40 mg ×1, repeated every 6 months
During the Extension Period, participants continued with either single injections every 6 or 12 months, based on their Core Period assignment.
PlaceboDrug
Placebo (saline solution for injection) was administered intra-articularly in various regimens to maintain blinding and ensure consistency in injection frequency across all arms:
- Arm 2: Placebo Q4W ×3 administered six months after LNA043 Q4W ×3
- Arm 4: Two placebo injections following LNA043 40 mg ×1 to complete the 3-injection cycle every 6 months
- Placebo Arm: Placebo Q4W ×3 every 6 months throughout the Core and Extension Periods.
In the Extension Period, placebo injections were used to match the frequency of active arms.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: LNA043 40 mg Q4W x3, Q6m | Experimental | Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years. Receives: Drug: LNA043 |
| Arm 2: LNA043 40 mg Q4W x3, Q12m | Experimental | Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3).
Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding. Receives: Drug: LNA043; Drug: Placebo |
| Arm 3: LNA043 20 mg Q4W x3, Q6m | Experimental | Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years. Receives: Drug: LNA043 |
| Arm 4: LNA043 40 mg x1, Q6m | Experimental | Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years. Receives: Drug: LNA043; Drug: Placebo |
| Placebo | Placebo comparator | Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months.
Extension Period: One i.a. injection of placebo every 6 months for 2 years. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Cartilage Thickness in the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee at Week 104
The cartilage thickness in the cMTFC of the target knee was assessed by quantitative Magnetic Resonance Imaging (qMRI). The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness
Measured: Baseline, Week 104
Secondary outcomes (11)
Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point numeric rating scale (NRS) from 0 (no pain) to 10 (worst imaginable pain). The WOMAC pain subscale was calculated as the sum of the 5 pain items, ranging from 0 to 50, with higher scores indicating worse pain. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Measured: Baseline, Week 104
Change From Baseline in WOMAC Pain Walking on a Flat Surface Item at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC pain scale included five questions about pain during specific activities such as walking on a flat surface, going up or down stairs, during the night while in bed, sitting or lying down and standing upright. Each item was rated on an 11-point NRS from 0 (no pain) to 10 (worst imaginable pain). Scores were then re-scaled to normalized 0-100.
The change from baseline at Week 104 in WOMAC pain walking on a flat surface item score was assessed, where a negative change indicated improvement.
Measured: Baseline, Week 104
Change From Baseline in WOMAC Function Scale at Week 104
The WOMAC is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with OA of the hip or knee.
The WOMAC functional subscale included 17 questions that measured how OA affected their daily activities including going up and down stairs, sitting, standing, squatting to the floor, walking, getting in a car, shopping, putting on and taking off socks, getting out of bed, lying in bed, bathing, sitting, getting on and off the toilet, heavy domestic duties, and light domestic duties.
Each item was rated on an 11-point NRS from 0 (no limitation) to 10 (extreme limitation). The WOMAC functional subscale was calculated as the sum of the 17 pain items, ranging from 0 to 170, with higher scores indicating more severe limitations. Scores were then re-scaled to normalized 0-100. Change from baseline at Week 104 was assessed, where a negative change indicated improvement.
Measured: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Total Tibiofemoral Compartments (TFCs) in the Target Knee at Week 104
The cartilage thickness in the total TFC in the target knee was assessed by qMRI. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Measured: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Medial TFCs in the Target Knee at Week 104
The cartilage thickness in the medial TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Measured: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Lateral TFCs in the Target Knee at Week 104
The cartilage thickness in the lateral TFC in the target knee was assessed by qMRI at Week 104. The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness.
Measured: Baseline, Week 104
Change From Baseline at Week 104 in the Osteoarthritis Research Society International (OARSI) Physical Performance-based Assessment: 40-meter (4×10m) Fast-paced Walk Test
The OARSI 40-meter (4x10m) fast-paced walk test assessed walking speed and functional mobility over a short distance. Participants were instructed to walk as quickly and safely as possible along a 10-meter walkway, turn around a cone, and repeat the sequence four times for a total of 40 meters. The time taken to complete the 40 meters was recorded. A shorter time indicated better performance.
The change from baseline at Week 104 was assessed. A negative change from baseline indicated improvement in physical function.
Measured: Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 30-second Chair Stand Test
The OARSI 30-second chair stand test assessed the number of times a participant stood up from a seated position and sat back down within 30 seconds. A higher number of repetitions reflected better lower limb strength and physical function. The change from baseline was evaluated at Week 104. A positive change from baseline indicated an improvement in physical function.
Measured: Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 6-minute Walking Test
This performance-based endpoint assessed submaximal aerobic capacity and functional walking ability. Participants were instructed to walk as far as possible in six minutes along a standardized, level walkway, following the guidelines of the American Thoracic Society. The total distance walked in meters was recorded. A greater distance walked indicated better physical function.
The change from baseline was evaluated at Week 104. A positive change from baseline reflected an improvement in physical function.
Measured: Baseline, Week 104
Percentage of Participants With Loss of Medial Minimum Joint Space Width ≥0.70 mm From Baseline at Week 104
Percentage of participants who experienced loss of medial minimum joint space width ≥ 0.70 mm from baseline as measured by X-ray at Week 104
Measured: Baseline, Week 104
Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) Status
ADA status was categorized based on baseline and post-baseline results as follows:
Subjects with ADA-negative sample at baseline: Participants with a negative ADA result at baseline.
Subjects with ADA-positive sample at baseline: Participants with a positive ADA result at baseline.
Subjects with ADA-positive NAb sample at baseline: Participants with a positive ADA and neutralizing antibody (NAb) result at baseline.
Subjects with treatment-emergent ADA-positive: Participants with a positive ADA result post-baseline and a negative result at baseline.
Subjects with treatment-emergent ADA-negative: Participants with a negative ADA result at baseline and all post-baseline samples also negative.
Subjects with treatment-emergent ADA-inconclusive: Participants who did not meet any of the above definitions
Measured: From baseline up to end of study, assessed up to 3.6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start31 May 2021
- Primary completion29 Sep 2024
- Study completion29 May 2025
Why it stopped: Study early terminated due to lack of effect (did not meet primary/ secondary endpoints). This decision was not linked to safety concerns
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoarthritisStudies 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
- 576 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04864392
- Sponsor's protocol ID
- CLNA043A12202
- Other IDs
- 2020-004897-22, 2023-509937-37-00, 2023
- Acronym
- ONWARDS
- Status last verified
- Mar 2026
- First submitted
- 26 Feb 2021
- Last updated
- 2 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- 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
Publications
Gerwin N, Scotti C, Halleux C, Fornaro M, Elliott J, Zhang Y, Johnson K, Shi J, Walter S, Li Y, Jacobi C, Laplanche N, Belaud M, Paul J, Glowacki G, Peters T, Wharton KA Jr, Vostiar I, Polus F, Kramer I, Guth S, Seroutou A, Choudhury S, Laurent D, Gimbel J, Goldhahn J, Schieker M, Brachat S, Roubenoff R, Kneissel M. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. Nat Med. 2022 Dec;28(12):2633-2645. doi: 10.1038/s41591-022-02059-9. Epub 2022 Dec 1.
PubMed 36456835
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 5-year, Randomized, Double-blind, Placebo-controlled, Multi-center Study Assessing the Efficacy, Safety, and Tolerability of Intra-articular Regimens of LNA043 Versus Placebo in Patients With Symptomatic Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT04864392
- Acronym / sponsor ID
- ONWARDS / CLNA043A12202
- Conditions
- Osteoarthritis
- Keywords
- LNA043, knee, arthritis, OA, knees
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study early terminated due to lack of effect (did not meet primary/ secondary endpoints). This decision was not linked to safety concerns
- Enrolment
- 576 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 May 2021 (actual)
- Primary completion
- 29 Sep 2024 (actual)
- Study completion
- 29 May 2025 (actual)
- First posted
- 28 Apr 2021 (actual)
- Results
- Posted 30 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis.
Detailed description
The study was structured as a two-period design:
- A 2-year Core Period, followed by
- A 3-year Extension Period, consisting of 2 years of continued treatment and 1 year of follow-up, totaling 5 years.
Participants were randomized in a 1:1:1:1:1 ratio into five treatment arms:
- LNA043 20 mg Q4w ×3, repeated every 6 months.
- LNA043 40 mg ×1 and placebo Q4w ×2, repeated every 6 months.
- LNA043 40 mg Q4w ×3 followed six months later by placebo Q4w ×3, repeated every 12 months.
- LNA043 40 mg Q4w ×3, repeated every 6 months.
- Placebo Q4w ×3, repeated every 6 months.
All injections were administered intra-articularly (i.a.) to the target knee. Placebo injections (saline solution) were used throughout the study to maintain blinding and ensure consistency in injection frequency across arms.
During the Extension Period:
- Participants from the 6-month cycle arms continued with a single injection of the same LNA043 dose every 6 months.
- Participants from the 12-month cycle arm received LNA043 40 mg every 12 months and placebo every other 6 months.
- Participants who received placebo during the Core Period continued with a single injection of the same placebo every 6 months.
The final year of the Extension Period was a no-treatment follow-up phase for all participants.
The study was terminated early following the Week 104 primary endpoint analysis due to lack of effect.There was no safety related reasons for early termination or safety concerns for the subjects in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1: LNA043 40 mg Q4W x3, Q6m | Experimental | Drug: LNA043Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years. |
| Arm 2: LNA043 40 mg Q4W x3, Q12m | Experimental | Drug: LNA043, Drug: PlaceboCore Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3). Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding. |
| Arm 3: LNA043 20 mg Q4W x3, Q6m | Experimental | Drug: LNA043Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years. |
| Arm 4: LNA043 40 mg x1, Q6m | Experimental | Drug: LNA043, Drug: PlaceboCore Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years. |
| Placebo | Placebo comparator | Drug: PlaceboCore Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of placebo every 6 months for 2 years. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males and females between 40 and 75 years of age
- Body mass index (BMI) < 40 kg/m2
- Diagnosis of primary tibiofemoral knee OA by standard American College of Rheumatology clinical and radiographic criteria
Key exclusion criteria (3 listed)
- Participants with radiographic knee OA K-L grade = 4 on the non-target knee
- Arthroscopy of the target knee within the 6 months prior to Screening
- Hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/μL
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 was administered intra-articularly in various dosing regimens across four active treatment arms: * Arm 1: LNA043 40 mg Q4W ×3, repeated every 6 months * Arm 2: LNA043 40 mg Q4W ×3, followed six months later by placebo Q4W ×3, repeated every 12 months * Arm 3: LNA043 20 mg Q4W ×3, repeated every 6 months * Arm 4: LNA043 40 mg ×1, repeated every 6 months During the Extension Period, participants continued with either single injections every 6 or 12 months, based on their Core Period assignment. | Drug | Arm 1: LNA043 40 mg Q4W x3, Q6m, Arm 2: LNA043 40 mg Q4W x3, Q12m, Arm 3: LNA043 20 mg Q4W x3, Q6m, Arm 4: LNA043 40 mg x1, Q6m |
| PlaceboPlacebo (saline solution for injection) was administered intra-articularly in various regimens to maintain blinding and ensure consistency in injection frequency across all arms: * Arm 2: Placebo Q4W ×3 administered six months after LNA043 Q4W ×3 * Arm 4: Two placebo injections following LNA043 40 mg ×1 to complete the 3-injection cycle every 6 months * Placebo Arm: Placebo Q4W ×3 every 6 months throughout the Core and Extension Periods. In the Extension Period, placebo injections were used to match the frequency of active arms. | Drug | Arm 2: LNA043 40 mg Q4W x3, Q12m, Arm 4: LNA043 40 mg x1, Q6m, Placebo |
Primary outcome
Change From Baseline in Cartilage Thickness in the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee at Week 104
Time frame: Baseline, Week 104
The cartilage thickness in the cMTFC of the target knee was assessed by quantitative Magnetic Resonance Imaging (qMRI). The change from baseline at Week 104 was calculated. A negative change from baseline indicated a reduction in the cartilage thickness
11 secondary outcomes
Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Scale at Week 104
Time frame: Baseline, Week 104
Change From Baseline in WOMAC Pain Walking on a Flat Surface Item at Week 104
Time frame: Baseline, Week 104
Change From Baseline in WOMAC Function Scale at Week 104
Time frame: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Total Tibiofemoral Compartments (TFCs) in the Target Knee at Week 104
Time frame: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Medial TFCs in the Target Knee at Week 104
Time frame: Baseline, Week 104
Change From Baseline in Cartilage Thickness in the Lateral TFCs in the Target Knee at Week 104
Time frame: Baseline, Week 104
Change From Baseline at Week 104 in the Osteoarthritis Research Society International (OARSI) Physical Performance-based Assessment: 40-meter (4×10m) Fast-paced Walk Test
Time frame: Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 30-second Chair Stand Test
Time frame: Baseline, Week 104
Change From Baseline at Week 104 in the OARSI Physical Performance-based Assessments: 6-minute Walking Test
Time frame: Baseline, Week 104
Percentage of Participants With Loss of Medial Minimum Joint Space Width ≥0.70 mm From Baseline at Week 104
Time frame: Baseline, Week 104
Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) Status
Time frame: From baseline up to end of study, assessed up to 3.6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36456835Gerwin N, Scotti C, Halleux C, Fornaro M, Elliott J, Zhang Y, Johnson K, Shi J, Walter S, Li Y, Jacobi C, Laplanche N, Belaud M, Paul J, Glowacki G, Peters T, Wharton KA Jr, Vostiar I, Polus F, Kramer I, Guth S, Seroutou A, Choudhury S, Laurent D, Gimbel J, Goldhahn J, Schieker M, Brachat S, Roubenoff R, Kneissel M. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. Nat Med. 2022 Dec;28(12):2633-2645. doi: 10.1038/s41591-022-02059-9. Epub 2022 Dec 1.
- A Plain Language Trial Summary is available on www.novctrd.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
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
75 sites in 15 countries: 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 Osteoarthritis, run by Novartis Pharmaceuticals at 75 sites in 15 countries.
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 3 inclusion and 3 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 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Australia, Spain, Czechia, Japan and 10 more countries. 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 30 Mar 2026). 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 Cartilage Thickness in the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee at Week 104 (time frame: Baseline, Week 104). 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 NCT04864392, which also lists 1 linked publication.
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 2 Apr 2026.