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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery
• Intervention / Treatment: Drug: LNA043; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNA043; LNA043 given intra-articularly	Drug: LNA043; ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
Placebo Comparator: Placebo; Placebo given intra-articularly	Drug: Placebo; ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to and including 7 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemical staining for LNA043 in knee cartilage	Joint presence and persistence of LNA043 within the cartilage of the knee	1 up to 4 weeks post-dose
Concentration of LNA043 in serum and synovial fluid	LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure	Pre-dose, Day 1, Day 4, Day 8, and Day 36
Concentration of ANGPTL in serum and synovial fluid	ANGPTL levels in serum and the synovial fluid	Pre-dose, Day 1, Day 4, Day 8, and Day 36
Presence of anti-LNA043	Immunogenicity in serum	Pre-dose, Day 8, and Day 36

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com
• Results for CLNA043X2101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2015
• Primary Completion (Actual): February 7, 2018
• Study Completion (Actual): March 6, 2018

Study Registration Dates

• First Submitted: June 23, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 8, 2015

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Primary Osteoarthritis, Total Knee Replacement, cartilage
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: CLNA043X2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No