Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery
Conditions
Keywords
Primary Osteoarthritis, Total Knee Replacement, cartilage
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.
Interventions
DRUGLNA043
ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
DRUGPlacebo
ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS) | Up to and including 7 days post-dose | Safety and tolerability of LNA043 after one intra-articular injection into the knee of osteoarthritis patients scheduled for total knee replacement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of anti-LNA043 | Pre-dose, Day 8, and Day 36 | Immunogenicity in serum |
| Immunohistochemical staining for LNA043 in knee cartilage | 1 up to 4 weeks post-dose | Joint presence and persistence of LNA043 within the cartilage of the knee |
| Concentration of LNA043 in serum and synovial fluid | Pre-dose, Day 1, Day 4, Day 8, and Day 36 | LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure |
| Concentration of ANGPTL in serum and synovial fluid | Pre-dose, Day 1, Day 4, Day 8, and Day 36 | ANGPTL levels in serum and the synovial fluid |
Countries
United States
Outcome results
None listed