Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery Clinical Trial
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
| Verified date | August 2018 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 28 |
| Est. completion date | March 6, 2018 |
| Est. primary completion date | February 7, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 50 Years to 75 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Novartis Investigative Site | Phoenix | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | Presence of anti-LNA043 | Immunogenicity in serum | Pre-dose, Day 8, and Day 36 |