Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis

NCT04864392 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CLNA043A122022020-004897-222023-509937-37-00
• Study Type: interventional
• Target: 576
• Locations: 14 countries
• Sites: 69

Brief Summary

This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis.

Conditions

Osteoarthritis

Keywords

LNA043; knee; arthritis; OA; knees

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, Week 104

Secondary Outcomes (11)

• Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Scale at Week 104

  Baseline, Week 104

• Change From Baseline in WOMAC Pain Walking on a Flat Surface Item at Week 104

  Baseline, Week 104

• Change From Baseline in WOMAC Function Scale at Week 104

  Baseline, Week 104

• Change From Baseline in Cartilage Thickness in the Total Tibiofemoral Compartments (TFCs) in the Target Knee at Week 104

  Baseline, Week 104

• Change From Baseline in Cartilage Thickness in the Medial TFCs in the Target Knee at Week 104

  Baseline, Week 104

Study Arms (5)

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.

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.

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.

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.

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.

Drug: Placebo

Interventions

Placebo DRUG

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.

Arm 2: LNA043 40 mg Q4W x3, Q12m; Arm 4: LNA043 40 mg x1, Q6m; Placebo

LNA043 DRUG

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.

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

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (75)

Elite Clinical Studies

Phoenix, Arizona, 85018, United States

Location

Tucson Orthopedic Institute PC

Tucson, Arizona, 85712, United States

Location

Sharps Hospital Grossmont

La Mesa, California, 91942, United States

Location

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Long Beach Clinical Trials

Long Beach, California, 90806, United States

Location

Artemis Institute Clinical Research

Riverside, California, 92503, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Arthemis Clinical Research

San Diego, California, 92103, United States

Location

Stamford Therapeutics Consortium LLC

Stamford, Connecticut, 06905, United States

Location

Sensible Healthcare

Ocoee, Florida, 34761, United States

Location

Clinical Research of West Florida Inc

Tampa, Florida, 33603, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Chicago Clinical Research Inst

Chicago, Illinois, 60607, United States

Location

Tandem clinical research

Marrero, Louisiana, 70072, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Center For Pharmaceutical Research

Kansas City, Missouri, 64114, United States

Location

Drug Trials America

Hartsdale, New York, 10530, United States

Location

AMR Knoxville

Knoxville, Tennessee, 37920, United States

Location

Metroplex Clinical Research

Dallas, Texas, 75231, United States

Location

Pioneer Research Solutions

Sugar Land, Texas, 77479, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Annapolis Rheumatology LLC

Fairfax, Virginia, 22033, United States

Location

Virginia Ispine Physicians PC

Richmond, Virginia, 23238, United States

Location

Novartis Investigative Site

Caba, C1428AZF, Argentina

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Novartis Investigative Site

Córdoba, X5000EOC, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, 4000, Argentina

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Novartis Investigative Site

Broadmeadow, New South Wales, 2292, Australia

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Novartis Investigative Site

Maroochydore, Queensland, 4558, Australia

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Novartis Investigative Site

Woodville South, South Australia, 5011, Australia

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Novartis Investigative Site

Hobart, Tasmania, 7000, Australia

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Novartis Investigative Site

Malvern East, Victoria, 3145, Australia

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Novartis Investigative Site

Christchurch, 8011, Australia

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Novartis Investigative Site

St Leonards, 2065, Australia

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Novartis Investigative Site

Waikanae Beach, 5036, Australia

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Novartis Investigative Site

Québec, Quebec, G1V 3M7, Canada

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Novartis Investigative Site

Trois-Rivières, Quebec, G9A 3Y2, Canada

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Novartis Investigative Site

Beijing, Beijing Municipality, 100044, China

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Novartis Investigative Site

Bengbu, 233004, China

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Novartis Investigative Site

Brno, Czech Republic, 66250, Czechia

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Novartis Investigative Site

Pardubice, Czech Republic, 530 02, Czechia

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Novartis Investigative Site

Brno-Zidonice, CZE, 61500, Czechia

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Novartis Investigative Site

Brno, 638 00, Czechia

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Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

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Novartis Investigative Site

Aarhus N, 8200, Denmark

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Novartis Investigative Site

Gandrup, 9362, Denmark

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Novartis Investigative Site

Vejle, 7100, Denmark

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Novartis Investigative Site

Tallinn, 10128, Estonia

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Novartis Investigative Site

Tartu, 50708, Estonia

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Novartis Investigative Site

Vadodara, Gujarat, 390022, India

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Novartis Investigative Site

Belagavi, Karnataka, 590010, India

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Novartis Investigative Site

Lucknow, Uttar Pradesh, 226003, India

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Novartis Investigative Site

Pune, 411019, India

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Novartis Investigative Site

Shinagawa, Tokyo, 140 0014, Japan

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Novartis Investigative Site

Shinjuku Ku, Tokyo, 160-0008, Japan

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Novartis Investigative Site

Suginami, Tokyo, 166-0002, Japan

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Novartis Investigative Site

Chuoh-ku, 104-0031, Japan

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Novartis Investigative Site

Osaka, 543-0027, Japan

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Novartis Investigative Site

Guadalajara, Jalisco, 44650, Mexico

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Novartis Investigative Site

Culiacán, Sinaloa, 80000, Mexico

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Novartis Investigative Site

Ciudad de, CP 06700, Mexico

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Novartis Investigative Site

Kielce, 25-017, Poland

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Novartis Investigative Site

Krakow, 31-501, Poland

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Novartis Investigative Site

Poznan, 60-446, Poland

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Novartis Investigative Site

Warsaw, 02-677, Poland

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Novartis Investigative Site

Santiago, A Coruna, 15705, Spain

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Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

A Coruña, 15006, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Seville, 41010, Spain

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Novartis Investigative Site

Changhua, 50006, Taiwan

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Novartis Investigative Site

Tainan, 704302, Taiwan

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Novartis Investigative Site

Glasgow, Scotland, G51 4TF, United Kingdom

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Novartis Investigative Site

Barnet, EN5 3DJ, United Kingdom

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Novartis Investigative Site

Norwich, NR4 7UY, United Kingdom

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Related Publications (1)

• 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.

  PMID: 36456835 DERIVED

Related Links

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

MeSH Terms

Conditions

Osteoarthritis; Arthritis

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@Novartis.com

+1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: April 28, 2021
• Study Start: May 31, 2021
• Primary Completion: September 29, 2024
• Study Completion: May 29, 2025
• Last Updated: April 2, 2026
• Results First Posted: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (3); CA (2); CZ (5); GB (3); US (23); JP (5); PL (4); TW (2); IN (4); AU (8); ES (2); CN (2); ME (3); AR (3)