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First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement

Primary Purpose

Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LNA043

Placebo

About this trial

This is an interventional other trial for Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery focused on measuring Primary Osteoarthritis, Total Knee Replacement, cartilage

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Male and female patients age 50 to 75 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening
Patients diagnosed with primary osteoarthritis of the knee assessed locally for whom a total knee replacement is planned
General health status acceptable for total knee replacement surgery in the opinion of the investigator
Stable medications within 3 months prior to enrollment (such as appropriate pain medication, antibiotics prophylaxis) and standard of care

Key Exclusion Criteria:

Presence of inflammatory arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout), active acute or chronic infection, or systemic cartilage disorder
Prior cartilage repair surgery, e.g. microfracture, autologous cartilage implantation (ACI) or else, at the same knee
Any surgical therapy or local treatment i.a. into the knee (viscosupplementation) to the knee within 2 months prior to enrollment
BMI > 40; presence of uncontrolled diabetes or hyperthyroidism
Large effusion in the knee to be replaced, more than (>)1 cm fluid in the suprapatellar space at the midline
Corticosteroid use by any route except topical and nasal in the 3 months prior to enrollment
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LNA043

Placebo

Arm Description

LNA043 given intra-articularly

Placebo given intra-articularly

Outcomes

Primary Outcome Measures

Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS)

Safety and tolerability of LNA043 after one intra-articular injection into the knee of osteoarthritis patients scheduled for total knee replacement

Secondary Outcome Measures

Immunohistochemical staining for LNA043 in knee cartilage

Joint presence and persistence of LNA043 within the cartilage of the knee

Concentration of LNA043 in serum and synovial fluid

LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure

Concentration of ANGPTL in serum and synovial fluid

ANGPTL levels in serum and the synovial fluid

Presence of anti-LNA043

Immunogenicity in serum

Full Information

NCT ID

NCT02491281

First Posted

June 23, 2015

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02491281

Brief Title

First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement

Official Title

A Randomized, Placebo Controlled, Double-blind First-in-human Single Ascending Dose Study of LNA043 in Primary Osteoarthritis Patients Scheduled for Total Knee Replacement

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

November 16, 2015 (Actual)

Primary Completion Date

February 7, 2018 (Actual)

Study Completion Date

March 6, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is designed to evaluate the safety and tolerability of ascending single doses of LNA043 given intra-articularly into the human knee joint prior to its removal at total knee replacement surgery. In addition, this will help to establish the presence of LNA043 within the articular cartilage, assess pharmacokinetics and immunogenicity, and will allow exploration of biomarkers of hyaline cartilage repair.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery

Keywords

Primary Osteoarthritis, Total Knee Replacement, cartilage

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LNA043

Arm Type

Experimental

Arm Description

LNA043 given intra-articularly

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo given intra-articularly

Intervention Type

Drug

Intervention Name(s)

LNA043

Intervention Description

ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery

Primary Outcome Measure Information:

Title

Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS)

Description

Safety and tolerability of LNA043 after one intra-articular injection into the knee of osteoarthritis patients scheduled for total knee replacement

Time Frame

Up to and including 7 days post-dose

Secondary Outcome Measure Information:

Title

Immunohistochemical staining for LNA043 in knee cartilage

Description

Joint presence and persistence of LNA043 within the cartilage of the knee

Time Frame

1 up to 4 weeks post-dose

Title

Concentration of LNA043 in serum and synovial fluid

Description

LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure

Time Frame

Pre-dose, Day 1, Day 4, Day 8, and Day 36

Title

Concentration of ANGPTL in serum and synovial fluid

Description

ANGPTL levels in serum and the synovial fluid

Time Frame

Pre-dose, Day 1, Day 4, Day 8, and Day 36

Title

Presence of anti-LNA043

Description

Immunogenicity in serum

Time Frame

Pre-dose, Day 8, and Day 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Male and female patients age 50 to 75 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening Patients diagnosed with primary osteoarthritis of the knee assessed locally for whom a total knee replacement is planned General health status acceptable for total knee replacement surgery in the opinion of the investigator Stable medications within 3 months prior to enrollment (such as appropriate pain medication, antibiotics prophylaxis) and standard of care Key Exclusion Criteria: Presence of inflammatory arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout), active acute or chronic infection, or systemic cartilage disorder Prior cartilage repair surgery, e.g. microfracture, autologous cartilage implantation (ACI) or else, at the same knee Any surgical therapy or local treatment i.a. into the knee (viscosupplementation) to the knee within 2 months prior to enrollment BMI > 40; presence of uncontrolled diabetes or hyperthyroidism Large effusion in the knee to be replaced, more than (>)1 cm fluid in the suprapatellar space at the midline Corticosteroid use by any route except topical and nasal in the 3 months prior to enrollment History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases Pregnant or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant

Facility Information:

Facility Name

Novartis Investigative Site

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85053

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing 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

Links:

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=454

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17358

Description

Results for CLNA043X2101 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement

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