Clinical trial NCT06779071: Pivotal Clinical Trial to Evaluate the Efficacy and Safety After NPNP-001 Application in Patients with Knee Osteoarthritis.
Official title: A Multicenter, Randomized, Double-blinded, Active-controlled, Non-inferiority, Pivotal Clinical Trial to Evaluate the Efficacy and Safety in Pain Reduction After NPNP-001 Application in the Knee Joint of Patients with Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Knee Osteoarthritis
Keywords: Polynucleotide sodium
Osteoarthritis
Lead sponsor: PharmaResearch Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2025-01-16
Enrollment: 260
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to demonstrate non-inferiority and safety in pain reduction after NPNP-001 application in patients with knee osteoarthritis.


Eligibility criteria: Inclusion Criteria:

1. Adult males and females aged 40 years or older as of the date of written consent
2. Patients diagnosed with unilateral or bilateral knee osteoarthritis according to the American College of Rheumatology (ACR) clinical diagnostic criteria, experiencing knee joint pain, and meeting at least three of the following conditions:

   * Age \> 50 years
   * Morning stiffness \< 30 minutes
   * Crepitus
   * Bony tenderness
   * Bony enlargement
   * No palpable warmth of the synovium
3. At least one knee joint with a Weight-Bearing Pain (100 mm-VAS) score ≥ 40 mm, measured at the screening visit
4. X-ray results from within 6 months prior to screening or at the screening visit indicating that the target lesion of knee osteoarthritis corresponds to Kellgren Lawrence Grade 1 to 3.
5. Patients with knee osteoarthritis who have not responded to conservative treatments such as pharmacotherapy or physical therapy for at least 3 months prior to screening.
6. Patients who can adequately understand and complete the efficacy assessment questionnaires.
7. Patients who voluntarily agree to the informed consent form after receiving an explanation of the purpose, methods, and effects of the clinical trial.
8. Patients who agree to refrain from using any pharmacotherapy for knee osteoarthritis other than the rescue medication during the clinical trial period.
9. Patients who are able to undergo allergy testing (skin prick test).

Exclusion Criteria:

1. Patients with a Body Mass Index (BMI) ≥ 35 kg/m² at screening.
2. Patients with rheumatoid arthritis or other types of arthritis such as traumatic, metabolic, etc.
3. Patients with conditions that are deemed likely to affect the efficacy and safety assessment of this clinical trial (however, those who are considered eligible by the investigator may be enrolled):

   * Patients with severe painful conditions such as septic arthritis, autoimmune diseases, gout, recurrent pseudogout, Paget's disease, etc.(e.g. Sudeck's atrophy, herniated discs, etc.), as well as those with joint fractures, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary osteochondrosis, genetic diseases (hyperkinesis, etc.), collagen gene abnormalities
   * Patients with hemorrhagic disorders, hemostatic disorders, CNS diseases, cancer, AIDS, heart disease, kidney disease, uncontrolled diabetes and hypertension, severe medical or psychiatric conditions, and patients with hypersensitivity to local anesthetics.
4. Patients with severe osteoarthritis symptoms in other joints (e.g., hip joint) that may affect pain assessment in the knee joint (polyarticular joint pain).
5. Patients with skin abnormalities at the injection site that may affect invasive procedures, such as infections or skin diseases.
6. Patients who have received the following medications prior to screening:

   A. Patients who have received sodium polynucleotide and/or hyaluronic acid(HA) injections into the target knee joint within 6 months prior to screening.

   B. Patients who have received steroid injections into the target knee joint within 3 months prior to screening.

   C. Patients who have used systemic steroids within 1 month prior to screening (topical and inhaled steroids are excluded).

   D. Patients who have received cell therapy or gene therapy into the target knee joint prior to screening.
7. Patients with severe joint effusion confirmed through tests such as the patellar tap test.
8. Patients who have undergone surgical procedures on the target knee joint or cartilage regeneration surgeries (such as microfracture, autologous chondrocyte implantation, etc.) within 6 months prior to screening (however, patients with surgical history on the opposite knee or hip joints will only be excluded if it is likely to impact the clinical evaluation of the target knee joint).
9. Patients with a history of knee joint replacement surgery in the target joint.
10. Patients who have taken anticoagulants (including warfarin, NOACs \[Non-vitamin K Oral Anti-Coagulants\], antiplatelet agents \[aspirin, clopidogrel; however, low-dose aspirin \[100 mg, maximum 300 mg/day\] is excluded\], thrombolytics \[urokinase, alteplase, etc.\]) within 2 weeks prior to the application of the investigational device.
11. Patients with a positive allergy test (skin prick test) result for the investigational device conducted at screening or those with hypersensitivity to components of the investigational device used in this clinical trial (including allergies to salmon, shrimp, and crab).
12. Patients who have participated in another clinical trial and received investigational products or medical devices within 6 months prior to screening.
13. Pregnant or breastfeeding women, women of childbearing potential who plan to become pregnant during the clinical trial period and for 3 months after, or men who do not intend to use appropriate contraceptive methods\*.

    * Hormonal contraceptives, intrauterine devices (such as Implanon), dual barrier methods (using both male condoms and cervical caps), and sterilization procedures (vasectomy, bilateral tubal ligation, etc.).
14. Patients with knee joint instability.
15. Patients who are expected to start medication for depression or anxiety disorders during the clinical trial period.

Primary outcomes:
measure: Change from baseline of Weight-bearing pain (WBP) - 100mm visual analogue scale (VAS)
timeFrame: 20 weeks
Secondary outcomes:
measure: Change from baseline of Weight-bearing pain (WBP) - 100mm visual analogue scale (VAS)
timeFrame: 3, 4, 8, 28 weeks
measure: Change from baseline of Rest pain - 100mm visual analogue scale (VAS)
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Change from baseline of Motion pain - 100mm visual analogue scale (VAS)
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Change from baseline of Patient Global Assessment (PGA) - 100mm visual analogue scale (VAS)
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Change from baseline of Investigator Global Assessment (IGA) - 100mm visual analogue scale (VAS)
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Change from baseline of WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) total score and individual score evaluation (Pain, Function, Stiffness)
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Change from baseline in EQ-5D (EuroQol-5 Dimension Health Questionnaire) Index and EQ VAS(visual analogue scale) assessment to measure quality of life
timeFrame: 3, 4, 8, 20, 28 weeks
measure: Proportion (%) of participants who took rescue medication at each visit following the application of the investigational device, and consumption
timeFrame: 0, 1, 2, 3, 4, 8, 20, 28 weeks
measure: Response Rate following the application of the investigational device
timeFrame: 8, 20, 28 weeks
measure: Physical assessments at each visit following the application of the investigational device: Swelling, Tenderness on pressure, Range of motion(ROM)
timeFrame: From 0 to 28 weeks
Other outcomes:
measure: The incidence rate of Pre-treatment adverse events (AEs), treatment-emergent adverse events (TEAEs), Solicited Local AEs and the Serious TEAEs
timeFrame: From 0 to 28 weeks
measure: The incidence rate of abnormal CS at Post-Treatment on Laboratory
timeFrame: From 0 to 28 weeks
measure: The incidence rate of abnormal clinical significance (CS) at Post-Treatment on Electrocardiogram
timeFrame: From 0 to 28 weeks
measure: The incidence rate of abnormal on Physical Examination
timeFrame: From 0 to 28 weeks
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul ST. Mary's Hospital
Study officials:
References: