Clinical trial NCT02491281: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery
Keywords: Primary Osteoarthritis, Total Knee Replacement, cartilage
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-07-08
Enrollment: 28
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS)
timeFrame: Up to and including 7 days post-dose
Secondary outcomes:
measure: Immunohistochemical staining for LNA043 in knee cartilage
timeFrame: 1 up to 4 weeks post-dose
measure: Concentration of LNA043 in serum and synovial fluid
timeFrame: Pre-dose, Day 1, Day 4, Day 8, and Day 36
measure: Concentration of ANGPTL in serum and synovial fluid
timeFrame: Pre-dose, Day 1, Day 4, Day 8, and Day 36
measure: Presence of anti-LNA043
timeFrame: Pre-dose, Day 8, and Day 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
Study officials:
References: