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

NCT03275064 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CLNA043X22022016-004052-30CTI-194705
• Study Type: interventional
• Target: 142
• Locations: 3 countries
• Sites: 19

Brief Summary

The purpose of this two-part study is to assess the efficacy, safety and tolerability of multiple intra-articular (i.a.) injections of LNA043, in regenerating the articular surface in patients with cartilage lesions of the knee (Part A) and knee osteoarthritis (Part B).

Conditions

Osteoarthritis

Keywords

Articular cartilage; partial thickness cartilage lesion; knee cartilage; regeneration; osteoarthritis; adult

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Articular Cartilage Collagen Organization in the Overall Cartilage (Femoral and Patellar Lesions) - Part A

  Collagen fibril organization in articular cartilage evaluated by Magnetic Resonance Imaging (MRI) from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.

  Baseline up to Week 16, Week 28

• Change From Baseline in Articular Cartilage Collagen Organization in the Deep Cartilage Layer (Femoral and Patellar Lesions) - Part A

  Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality). The area of interest is the focal cartilage lesion.

  Baseline up to Week 16, Week 28

• Change From Baseline in Articular Cartilage Collagen Organization in the Superficial Cartilage Layer (Femoral and Patellar Lesions) - Part A

  Collagen fibril organization in articular cartilage evaluated by MRI from the cartilage mean T2 relaxation time (with lower values indicative of higher quality).The area of interest is the focal cartilage lesion.

  Baseline up to Week 16, Week 28

• Change From Baseline of LNA043 to Placebo in Cartilage Volume in the Femoral Medial Index Region (mm3) - Part B

  MRI based quantitative assessment using an automated segmentation algorithm

  Baseline, Week 29, Week 53

• Change From Baseline of LNA043 to Placebo in Cartilage Thickness in the Femoral Medial Index Region (mm) - Part B

  MRI based quantitative assessment using an automated segmentation algorithm.

  Baseline, Week 29, Week 53

• Overview of Number of Participants With Adverse Events and Serious Adverse Events for Part A and Part B

  Treatment emergent other and serious adverse events (TEAE and TESAE) period: Part A: Baseline up to Day 50 (included 30 day safety follow-up Part B: Baseline up to Day 113 (included 30 day safety follow-up) Long term Follow-UP period: Part A: Day 51 to Day 365 Part B: Day 114 to Day 365

  Baseline up to end of post treatment follow-up

Secondary Outcomes (14)

• Change From Baseline of LNA043 to Placebo in Cartilage Defect Volume (mm^3) for Both Groups of Patients (Femoral and Patellar Lesions) - Part A

  Baseline up to Week 16, Week 28

• Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Overall Part B

  Baseline, Week 29, Week 53

• Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Deep Part B

  Baseline, Week 29, Week 53

• Change From Baseline in Cartilage Mean T2 Relaxation Time as a Marker of Collagen Organization in the Medial Femoral Index Region - Superficial Part B

  Baseline, Week 29, Week 53

• Incidence of Immunogenicity (IG) Part A

  Week 1,3,8,16,28

Study Arms (5)

LNA043 40 mg Part B

EXPERIMENTAL

LNA043 40 mg Part B

Biological: LNA043

LNA043 20 mg Part B

EXPERIMENTAL

LNA043 20 mg Part B

Biological: LNA043

LNA043 20 mg Part A

EXPERIMENTAL

LNA043 20 mg Part A

Biological: LNA043

Placebo Part A

PLACEBO COMPARATOR

Placebo Part A

Other: Placebo

Placebo Part B

PLACEBO COMPARATOR

Placebo Part B

Other: Placebo

Interventions

LNA043 BIOLOGICAL

LNA043 intra-articular injection

LNA043 20 mg Part A; LNA043 20 mg Part B; LNA043 40 mg Part B

Placebo OTHER

Placebo intra-articular injection

Placebo Part A; Placebo Part B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient was ≥18 and ≤55 years old at time of screening.
• Patient had a body mass index (BMI) \<30 kg/m2 at screening,
• Patient had a symptomatic, single, articular cartilage defect of one knee, grade II or IIIA according to the ICRS classification, localized to either the femoral condyles/femoral trochlea or to the patella, based on MRI or arthroscopy performed within 9 months before screening visit and confirmed by screening 3T MRI.
• Patient had an onset of pain and impairment of function between two (2) months and two (2) years before screening.
• Patient had a grade 2 or 3 OA of the knee with Joint Space Width (JSW) 2-4 mm evaluated with X-Ray at screening
• Patient was ≥18 and ≤75 years old at time of screening.
• Patient had a body mass index (BMI) ≤ 35 kg/m2 at screening
• Diagnosis of femorotibial osteoarthritis (OA) in the target knee by standard American College of Rheumatology (ACR) criteria at study start (clinical AND radiographic criteria)
• Patient must have had symptomatic disease predominantly in one (the index) knee, with minimal or no symptoms in the contralateral knee. Symptomatic disease is defined as having pain in the knee more than 50% of the days during the last 3 months from screening.
• Patient had a K\&L grade 2 or 3 OA of the knee with JSW 2.00-4.00 mm (X=0.225) fixed position evaluated with X-Ray by the Central Reader at screening.

You may not qualify if:

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 15 days after stopping of investigational drug.
• Patient had surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy \>50% (Note: prior diagnostic arthroscopy with debridement and lavage, \<50% meniscectomy, lateral release, patellar realignment, medial patellofemoral ligament reconstruction are acceptable if performed at least 2 months prior to screening; anteriorcruciate ligament reconstrucion is acceptable if performed 12 months prior to screening, or less if restoration of joint function is evident, and agreed by the sponsor).
• Patient had an unstable target knee joint or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
• Prohibited medication updated with reference to dosing (formerly screening).
• Regular smokers (\> 5 cigarettes/day). Urine cotinine levels will be measured during screening for all patients. Regular smokers will be defined as any patient who reports tobacco use of \> 5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.
• Patient had radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2 based on X-ray evaluation performed within 9 months from screening.
• Patient had patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation performed within 9 months from screening
• Patient had malalignment (valgus- or varus-deformity) in the target knee ≥ 5° based on X-ray evaluation performed within 9 months from screening. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.
• Regular smokers (\> 10 cigarettes/day).
• Clinical signs of inflammation (i.e., redness) in the target knee.
• History of knee replacement (unilateral or total) in either knee.
• Presence of severe hip OA conditioning lower limb function according to PI's evaluation.
• Nephrotic syndrome and/or significant proteinuria
• History of coagulopathy or medical condition requiring anticoagulation which would preclude knee injection
• Patient had malalignment (valgus- or varus-deformity) in the target knee ≥ 7.5° based on X-ray evaluation. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Arizona Research

Phoenix, Arizona, 85053, United States

Location

Scott A Hacker MD Medical Group d b a Horizon Clinical Res

La Mesa, California, 91942, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Precision Clinical Research LLC

Sunrise, Florida, 33351, United States

Location

Clinical Research of West Florida Inc

Tampa, Florida, 33606, United States

Location

St Lukes Intermountain Research Center

Boise, Idaho, 83702, United States

Location

Midwest Orthopedics At Rush

Chicago, Illinois, 60612, United States

Location

Sundance Clinical Research LLC

St Louis, Missouri, 63141, United States

Location

LV Research

Las Vegas, Nevada, 89119, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Novartis Investigative Site

Brno, Czech Republic, 66250, Czechia

Location

Novartis Investigative Site

Mladá Boleslav, Czech Republic, 29301, Czechia

Location

Novartis Investigative Site

Kladno, 272 59, Czechia

Location

Novartis Investigative Site

Kolín, 280 02, Czechia

Location

Novartis Investigative Site

Pardubice, 53002, Czechia

Location

Novartis Investigative Site

Prague, 190 00, Czechia

Location

Novartis Investigative Site

Aarhus N, 8200, Denmark

Location

Novartis Investigative Site

Hvidovre, 2650, Denmark

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

For several outcomes there was a loss in samples size, which may limit the interpretability of results. For Part B, subgroup 1 was defined to address heterogeneity in MRI quality, and to ensure validity of the reported data. P-values for T2 relaxation time are omitted, as there was an error in the calculation. For Part A, the protocol sample size section refers to a ratio for the primary analysis, but data was reported as superficial and deep cartilage layers separately. Both will be updated.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A total of 142 participants were randomized, but only 141 received treatment. One participant in Part B was discontinued due to poor veins that were not adequate for blood samples.

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 7, 2017
• Study Start: September 12, 2017
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: April 21, 2026
• Results First Posted: February 14, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (2); CZ (6); US (11)