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

NCT02491281 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CLNA043X2101
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery

Keywords

Primary Osteoarthritis, Total Knee Replacement, cartilage

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Immunohistochemical staining for LNA043 in knee cartilage

  1 up to 4 weeks post-dose

• Concentration of LNA043 in serum and synovial fluid

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

• Concentration of ANGPTL in serum and synovial fluid

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

• Presence of anti-LNA043

  Pre-dose, Day 8, and Day 36

Study Arms (2)

LNA043

EXPERIMENTAL

LNA043 given intra-articularly

Drug: LNA043

Placebo

PLACEBO COMPARATOR

Placebo given intra-articularly

Drug: Placebo

Interventions

LNA043 DRUG

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

LNA043

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Phoenix, Arizona, 85053, United States

Location

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 novartisclinicatrials.com
• Results for CLNA043X2101 can be found on the Novartis Clinical Trial Results Website

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: July 8, 2015
• Study Start: November 16, 2015
• Primary Completion: February 7, 2018
• Study Completion: March 6, 2018
• Last Updated: December 11, 2020

Record last verified: 2018-08

Locations

US (1)