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Study on Safety, Tolerability Prelimenary Efficacy of LNA043 in Patients Undergoing Autologous Chondrocyte Implantation (ACI)

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ClinicalTrials.gov Identifier: NCT03334812
Recruitment Status : Completed
First Posted : November 7, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this (Proof of Concept) PoC study is to assess safety, tolerability and preliminary efficacy of intra articular (i.a.) LNA043 in regenerating the articular cartilage of the knee at the donor sites of the autologous chondrocyte implantation (ACI) procedure, with a hyaline tissue, significantly more often than with placebo.

Condition or disease Intervention/treatment Phase
Knee Cartilage Lesion Biological: LNA043 Biological: placebo to LNA043 Biological: LNA043 40mg/4ml Biological: placebo to LNA043 40mg/4ml Phase 2

Detailed Description:

The purpose of this (Proof of Concept) PoC study is to assess safety, tolerability and preliminary efficacy of intra articular (i.a.) LNA043 in regenerating the articular cartilage of the knee at the donor sites of the autologous chondrocyte implantation (ACI) procedure, with a hyaline tissue, significantly more often than with placebo. The highest single safe dose of LNA043 of the First in Human CLNA043X2101 study will be used.

This is 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). Approximately 22 patients will be enrolled in the study to allow 18 completers. Participants will be treated only on one occasion (Day 1) with a single i.a. injection that will be performed under arthroscopic visualization.

The primary efficacy variable, GAG content change and bi-layer collagen organization in the cartilage repair tissue at the donor sites based on 7T MRI at week 4, and key secondary endpoints, will be analyzed using a mixed model repeated measures (MMRM) analysis of variance model, including all timepoints, to compare treatment groups.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 19, 2017
Actual Primary Completion Date : April 5, 2019
Actual Study Completion Date : April 5, 2019

Arm Intervention/treatment
Experimental: LNA043
LNA043 20mg/3ml single dose
Biological: LNA043
LNA043 Single dose

Placebo Comparator: Matching placebo to 20mg
Matching placebo to 20mg/3ml, single dose
Biological: placebo to LNA043
placebo to LNA043 single dose

Experimental: LNA043 40mg/ml
LNA043 40mg/4ml single dose
Biological: LNA043 40mg/4ml
LNA043 40mg/4ml Single Dose

Placebo Comparator: Matching placebo to 40mg
Matching placebo to 40mg/4ml, single dose
Biological: placebo to LNA043 40mg/4ml
Matching placebo to 40 mg




Primary Outcome Measures :
  1. Cartilage GAG content based on MRI measurements [ Time Frame: 4 weeks ]
    Efficacy of a single LNA043 i.a. injection in regenerating hyaline cartilage tissue at the donor sites of patients undergoing autologous chondrocyte implantation (ACI)

  2. Bi-layer collagen organization based on MRI measurements [ Time Frame: 4 weeks ]
    Efficacy of a single LNA043 i.a. injection in regenerating hyaline cartilage tissue at the donor sites of patients undergoing autologous chondrocyte implantation (ACI)


Secondary Outcome Measures :
  1. ICRS II histology scoring and percentage of donor site filling based on MRI measurements [ Time Frame: 4 weeks ]
    Extent and quality of the repair tissue at the donor site before surgery

  2. Percentage of donor site filling based on MRI measurements. [ Time Frame: 12 and 28 weeks ]
    Extent and quality of filling of the donor site over a longer term

  3. PK profile of LNA043 and of AngPTL3 in serum Cmax [ Time Frame: 4 weeks ]
    Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration

  4. Presence and characterization of anti-LNA043 antibodies in serum [ Time Frame: Day 1, 8, 29, 85 and 197 ]
    Potential immunogenicity of LNA043

  5. Cartilage GAG content based on MRI measurements. [ Time Frame: 12 and 28 weeks ]
    Extent and quality of filling of the donor site over a longer term

  6. Bi-layer collagen organization based on MRI measurements. [ Time Frame: 12 and 28 weeks ]
    Extent and quality of filling of the donor site over a longer term

  7. PK profile of LNA043 and of AngPTL3 in serum AUC [ Time Frame: 4 weeks ]
    Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration



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 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed
  • Patient is ≥18 and≤ 45 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.

Exclusion Criteria:

  • 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).
  • 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.

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): NCT03334812


Locations
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Austria
Novartis Investigative Site
Graz, Austria, 8036
Novartis Investigative Site
Wien, Austria, 1090
Novartis Investigative Site
Wien, Austria, 1180
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03334812     History of Changes
Other Study ID Numbers: CLNA043X2201
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
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: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
cartilage lesion, ACI