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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03275064
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : May 22, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Wounds and Injuries Biological: LNA043 Other: Placebo Phase 2

Detailed Description:
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). In Part A, this study aims to establish Proof of Concept (PoC), namely regeneration of the articular cartilage, in order to provide information on the potential clinical utility of LNA043, with the ultimate goal of replacing current surgical procedures for cartilage repair with an injectable, less invasive regenerative therapy. In Part B, this study aims at further evaluating the cartilage anabolic activity of LNA043 in a more severe knee OA population, and at testing the potential benefit of a higher dose of LNA043 administered i.a. monthly instead of weekly.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Two-part, Randomized, Placebo-controlled, Patient and Investigator Blinded, Study Investigating the Safety, Tolerability and Preliminary Efficacy of Intra-articular LNA043 Injections in Regenerating the Articular Cartilage of the Knee in Patients With Articular Cartilage Lesions (Part A) and in Patients With Knee Osteoarthritis (Part B).
Actual Study Start Date : September 12, 2017
Estimated Primary Completion Date : March 25, 2022
Estimated Study Completion Date : March 25, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: LNA043 - lower dose (Part A)
Single i.a. injection of 20 mg [LNA043], once-weekly injections from Week 1 to Week 4 (Part A)
Biological: LNA043
LNA043 intra-articular injection

Placebo Comparator: Placebo (Part A)
Single i.a. injection of placebo to 20 mg [LNA043], once-weekly injections from Week 1 to Week 4 (Part A)
Other: Placebo
Placebo intra-articular injection

Experimental: LNA043 - higher dose (Part B)
Single i.a. injection of 40 mg [LNA043], once-monthly injection from week 1 to week 13 (Part B)
Biological: LNA043
LNA043 intra-articular injection

Experimental: LNA043 - Lower Dose (Part B)
Single i.a. injection of 20 mg [LNA043], once-monthly injection from week 1 to week 13 (Part B)
Biological: LNA043
LNA043 intra-articular injection

Placebo Comparator: Placebo (Part B)
Single i.a. injection placebo, once-monthly injection from week 1 to week 13 (Part B)
Other: Placebo
Placebo intra-articular injection




Primary Outcome Measures :
  1. Articular cartilage bi-layer collagen organisation evaluated with MRI and measured in milliseconds (ms) (Part A only) [ Time Frame: Up to Week 28 ]
    To assess the efficacy of multiple i.a. injections of LNA043 in regenerating the articular cartilage tissue

  2. Number of patients with any adverse events, serious adverse events and death (Part A and Part B) [ Time Frame: Up to 52 weeks ]
    To assess safety and local tolerability of multiple i.a. injections of LNA043

  3. Change in cartilage volume/thickness in the index region (Part B only) [ Time Frame: Up to Week 52 ]
    To assess the efficacy of multiple i.a. injections of LNA043 in regenerating the articular cartilage tissue


Secondary Outcome Measures :
  1. Change in volume of cartilage defect filling evaluated with MRI (Part A only) [ Time Frame: Week 16, Week 28 ]
    To assess the extent of the repair cartilage tissue following multiple i.a. injections of LNA043

  2. Maximum Observed Plasma Concentration measured in ng/mL (Part A and Part B) [ Time Frame: Part A: 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4; Part B: Week 1, Week 4, Week 9, Week 13, Week 16, Week 28 and Week 52 ]
    To evaluate systemic and local PK of LNA043 following multiple i.a. injections of LNA043

  3. Potential immunogenicity of LNA043 presence and characterisation of anti-LNA043 antibodies in serum (Part A and Part B) [ Time Frame: Week 1, Week 3, Week 6, Week 16, Week 28 ]
    To assess the potential immunogenicity of LNA043

  4. Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (Part A and Part B) [ Time Frame: Part A: 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4; Part B: Week 1, Week 4, Week 9, Week 13, Week 16, Week 28 and Week 52 ]
    To evaluate systemic and local PK of LNA043 following multiple i.a. injections of LNA043

  5. Articular cartilage bi-layer collagen organization evaluated with T2 relaxation times (in ms) (Part B only) [ Time Frame: Week 28, Week 52 ]
    To assess the extent of the repair cartilage tissue following multiple i.a. injections of LNA043



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria Part A

  • Patient is ≥18 and ≤55 years old at time of screening.
  • Patient has a body mass index (BMI) <30 kg/m2 at screening, for patients with BMI >30 but ≤ 33kg/m2, eligibility will be decided by consultation with the sponsor.
  • Patient has 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 has an onset of pain and impairment of function between two (2) months and two (2) years before screening.
  • Patient reports a KOOS (sports and recreational activities subscale) score of ≤ 60 at both screening and Day 1.

Inclusion criteria Part B

  • Patient is ≥18 and ≤75 years old at time of screening.
  • Patient has a body mass index (BMI) <35 kg/m2 at screening
  • Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at study start (clinical AND radiographic criteria)
  • Patient has a K&L grade 2 or 3 OA of the knee with JSW 2-4 mm evaluated with X-Ray at screening.
  • Patient must have 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.

Exclusion criteria Part A & B

  • 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 has 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 has an unstable target knee joint or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
  • Patient has patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation performed within 9 months from screening.
  • Patient has 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.

Prohibited medication updated with reference to dosing (formerly screening).

Exclusion Criteria Part A only

  • 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 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 9 months from screening.

Exclusion Criteria Part B only

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275064


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Arizona
Novartis Investigative Site Recruiting
Phoenix, Arizona, United States, 85053
Novartis Investigative Site Completed
Tucson, Arizona, United States, 85712
United States, California
Novartis Investigative Site Recruiting
La Mesa, California, United States, 91942
United States, Florida
Novartis Investigative Site Completed
Longwood, Florida, United States, 32750
Novartis Investigative Site Recruiting
Miami Lakes, Florida, United States, 33014
United States, Idaho
Novartis Investigative Site Completed
Boise, Idaho, United States, 83702
United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60612
United States, Indiana
Novartis Investigative Site Withdrawn
Greenwood, Indiana, United States, 46143
United States, Pennsylvania
Novartis Investigative Site Recruiting
Philadelphia, Pennsylvania, United States, 19140
Czechia
Novartis Investigative Site Completed
Brno, Czech Republic, Czechia, 66250
Novartis Investigative Site Completed
Mlada Boleslav, Czech Republic, Czechia, 29301
Novartis Investigative Site Completed
Kladno, Czechia, 272 59
Novartis Investigative Site Completed
Pardubice, Czechia, 53002
Denmark
Novartis Investigative Site Completed
Aarhus C, Denmark, DK 8000
Novartis Investigative Site Completed
Hvidovre, Denmark, 2650
Sweden
Novartis Investigative Site Withdrawn
Kungsbacka, Sweden, 434 80
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03275064    
Other Study ID Numbers: CLNA043X2202
2016-004052-30 ( EudraCT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Articular cartilage
partial thickness cartilage lesion
knee cartilage
regeneration
osteoarthritis
Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Wounds and Injuries
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases