Osteoarthritis, Knee
Conditions
Brief summary
This two-part study will be conducted in male and female patients, 30 - 80 years of age with painful OA of the index knee with Kellgren-Lawrence (K-L) Grade 2, 3 or 4. Part 1 - Single Ascending Dose (SAD) Phase: Up to three ascending doses of FX201 will be tested in cohorts of 5-8 patients. Each patient will only receive one injection of FX201. An independent Data Monitoring Committee (DMC) will review safety and guide the conduct of the study. Part 2 - Expansion Phase: Up to an additional 35 patients will be enrolled at each dose level reviewed by the DMC. Each patient will only receive one injection of FX201.
Detailed description
This two-part study will be conducted in male and female patients, 30 - 80 years of age with painful OA of the index knee with Kellgren-Lawrence (K-L) Grade 2, 3 or 4. Part 1 - SAD Phase: Up to three ascending doses of FX201 (low dose, mid dose and high dose) will be tested in cohorts of 5-8 patients. Each patient will only receive one injection of FX201. A maximum of 24 patients will be enrolled (range 15 to 24). When a minimum of 4 weeks have elapsed since the last patient of the current cohort has been treated, all safety data will be collected and reviewed by an independent Data Monitoring Committee (DMC). After evaluating cohort safety data, the DMC will evaluate continuing the trial and initiating treatment in the next dosing cohort as well as expanding enrollment in dose level(s). Part 2 - Expansion Phase: After the DMC has met to review safety data from each Cohort and has recommended expanding dose level(s), enrollment slots for dose levels reviewed by the DMC will be opened. A maximum of 105 patients \[up to an additional 35 patients per dose level (up to 20 FX201 alone and up to 15 FX201 with IA methylprednisolone 40 mg/mL pre-treatment)\].
Interventions
BIOLOGICALFX201
FX201, humantakinogene hadenovec, is a novel interleukin-1 receptor antagonist (IL-1Ra) gene therapy for IA administration that is being developed for the treatment of patients with OAK.
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
Part 1 - Open-Label, Single Ascending Dose Phase Part 2 - Open-Label, Expansion Phase to enroll additional patients in DMC-cleared dose levels by sequential assignment against a pre-defined randomized list
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Written consent to participate in the study * Male or female 30 to 80 years of age, inclusive, on the day of enrollment (Day 1) * Body mass index (BMI) ≤ 40 kilograms per meters squared (kg/m2) * Clinical diagnosis of OA of the knee on the American College of Rheumatology criteria (Altman, 1986) with radiologic evidence of OA (K-L Grade 2 or 3 for SAD Phase Cohort A and K-L Grade 2, 3 or 4 for SAD Phase Cohorts B and C and the Expansion Phase) at the index joint at the screening visit * Moderate pain in the index joint * Failed two or more types of conservative therapy for index knee osteoarthritis (e.g., structured exercise programs, topical or oral non-steroidal anti-inflammatory therapies); or failed one prior type of conservative therapy and at least one prior index knee IA treatment (corticosteroid or hyaluronic acid) * Sexually active females and males agree to use highly effective methods of contraception
Exclusion criteria
* Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease * History of or current infection in the index knee joint * Inability to undergo Magnetic Resonance Imaging (MRI) due to presence of surgical hardware or other foreign body in the index knee * Unstable index knee joint (e.g., torn anterior cruciate ligament, etc.) within 12 months of Screening * Any IA drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., IA corticosteroid, IA hyaluronic acid, platelet rich plasma injection, stem cells, prolotherapy and amniotic fluid injection, etc.) * Cold or radiofrequency nerve ablation of the index knee within 12 months of Screening * Arthroscopic or open surgery on the index knee within 12 months of Screening or planned/anticipated surgery on the index knee for the study period * Anticipated major surgery during the study period * Laboratory values that meet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measure: Incidence of treatment emergent adverse events after a single intra-articular (IA) injection of FX201 (safety and tolerability) | Baseline to Week 104 | Incidence of treatment emergent adverse events after a single intra-articular (IA) injection of FX201 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measure: Characterization of the systemic biodistribution of FX201 as seen through the percentage of patients positive for FX201 at Baseline, Day 1, Day 2, Week 1, Week 2, Week 3, and Week 4 | Baseline, Day 1, Day 2, Week 1, Week 2, Week 3, Week 4 | The percentage of patients positive for FX201 at select timepoints |
Countries
United States
Contacts
STUDY_DIRECTORWarren Rizzo, MD
Pacira Pharmaceuticals, Inc
Outcome results
None listed