Study of efficacy and safety of NaPPS in patients with knee osteoarthritis

JRCT ID: jRCT2071210131

Registered date:09/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: knee osteoarthritis
• Date of first enrollment: 09/03/2022
• Target sample size: 90
• Study type: Interventional
• Intervention(s): For patients with knee osteoarthritis, 2 mg / kg of body weight is subcutaneously administered once a week for 8 weeks (8 times in total). Additional doses will be administered for 6 more weeks (6 times in total). The dose should be administered to the left or right upper arm, left or right thigh, or left or right abdomen, and should be administered to a different site than the previous dose.

Outcome(s)

Primary Outcome

WOMAC - Overall Score
Evaluation using a questionnaire format to be completed by the patient. The questions are divided into three sections as follows
- Section A: Pain within 48 hours
- Section B: Stiffness
- Section C: Difficulty in performing daily activities
The total score of the three sections is the WOMAC overall score.
The WOMAC-overall scores for Visit 9 and Visit 11 in the evaluated knee will be compared to the WOMAC-over all scores for Visit 3 in the evaluated knee, and the amount of change and improvement rate will be compared to the placebo group.

Key inclusion & exclusion criteria

• Age minimum: >= 40age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

[At the time of provisional registration]
1) Patients diagnosed with knee osteoarthritis (hereinafter referred to as OA) according to the ACR classification criteria, excluding secondary OA, with standing frontal radiographic findings of grade 2 or higher on the K-L classification in the knee to be evaluated or both knees.
2) Patients with OA pain in the knee to be evaluated for at least one year prior to the provisional registration evaluation date (Visit 1), and the pain persists despite the use of drug therapy including regenerative medicine products.
3) WOMAC-A (pain) score and 50-foot (15-meter) walk test score are between NRS 5 and 9 for the evaluated knee and 3 or less for the non-evaluated knee.
WOMAC-A score: The average of the responses in Section A.
4) One or more of the four clinical findings of tenderness (medial articular facet, lateral articular facet, patellofemoral joint, and popliteal area) is observed in the knee to be evaluated.
5) Patient capable of conversation (able to explain or express their symptoms)
6) Age from 40 to less than 75 years old at the time of consent.
7) Patients who are expected to be able to perform all the observation items planned in the clinical trial and who agree to the implementation.
8) Patients who have agreed to follow the instructions of the investigator.
9) Patients who understand the purpose of the clinical trial and the study, understand the side effects, and have given written consent to participate in the clinical trial.
10) Japanese patients residing in Japan

[At the time of registration]
1) Patients whose WOMAC-A score during pre-administration observation and at the time of registration is between NRS 5 and 9 for the evaluated knee and 3 or less for the non-evaluated knee.
2) Patients whose WOMAC-A scores of the evaluated knee during pre-dose observation and at the time of enrollment are stable within +-20% of the score at the time of provisional registration.
3) Patients with at least one of the four clinical findings of tenderness (medial articular facet, lateral articular facet, patellofemoral joint, and popliteal area) in the knee to be evaluated.

Exclude criteria

[At the time of provisional registration]
1) Patients with any of the following complications
(1) Patients with a predisposition to bleeding (gastrointestinal bleeding such as gastric ulcer, duodenal ulcer, etc., or patients with suspected cerebral hemorrhage)
(2) Patients whose complications pose a therapeutic or safety problem due to the prohibition of concomitant administration of prohibited drugs during the period of administration of the investigational drug
(3) Patients with cardiovascular diseases (e.g., aneurysms) or hematological diseases (e.g., thrombocytopenia) that may pose a bleeding risk
(4) Patients with heparin-induced thrombocytopenia (HIT) type II
(5) Patients with serious allergic diseases or serious complications
(6) Patients with keloid diathesis
(7) Patients with complications or suspicious findings of maculopathy.
2) Patients with a history of any of the following
(1) Patients with a history of drug hypersensitivity to heparin or pentosan polysulfate
(2) Patients with a history of HIT type II
(3) Patients with a history of drug hypersensitivity or thrombocytopenia
(4) Patients with a history of severe food allergy
(5) Patients with a history of malignant tumor (except for patients who have not had metastasis or recurrence since complete resection and no treatment is required, and more than 5 years have passed as of the date of provisional registration)
3) Patients whose AST >100 IU/L, ALT >100 IU/L, or APTT values exceed the upper limit of the institutional reference values
4) Patients who have undergone a surgical procedure within 6 months (24 weeks) prior to obtaining consent, or are scheduled to undergo a surgical procedure during the study period
5) Patients who have participated in other clinical studies or clinical trials within 4 months (16 weeks) prior to obtaining consent, or who have used heparin or polysulfated pentosan products
6) Patients who have participated in the treatment or clinical trial of a regenerative medicine product within one year prior to obtaining consent.
7) Patients who have got platelet-rich plasma (PRP) therapy to the knee joint within 6 months (24 weeks) prior to obtaining consent.
8) Patients who received intra-articular administration of hyaluronic acid to the evaluated knee, systemic or intra-articular corticosteroid administration to the evaluated knee (excluding injection or topical application to other than the evaluated knee, or topical use such as inhalation or application) within 1 month (4 weeks) prior to the provisional registration evaluation date (Visit 1).
9) Patients who have received non-steroidal anti-inflammatory drugs (except for topical use other than the knees to be evaluated), acetaminophen (other than oral), muscle relaxants, narcotic analgesics, non-narcotic analgesics, drugs indicated for pain, or chondroitin products (except for ophthalmic use) within 7 days prior to the provisional registration evaluation date (Visit 1)
10) Patients who have taken oral acetaminophen within 2 days prior to the provisional registration evaluation date (Visit 1).
11) Patients who have taken supplements containing hyaluronic acid, glucosamine, chondroitin, or collagen since obtaining consent
12) Patients with significant functional impairment of the lower limb on the knee side to be evaluated due to fracture, trauma, etc.
13) Patients whose body weight exceeds 100 kg
14) Patients with alcoholism or drug dependence
15) Pregnant or lactating patients, or patients of childbearing potential who wish to become pregnant during the study period, or patients who are unable to consent to appropriate contraception (intrauterine device, spermicide, condom application by partner, etc.) (Pregnancy testing will be required at the time of registration and at defined time points during the study period)
16) Patients with a history of participation in the study (including participation in the observation period only)
17) Other patients who are judged by the investigator to have difficulty in answering or filling in the questionnaires necessary for the evaluation of the efficacy of the study or who are not appropriate for the safe conduct of the study.

[At the time of registration]
1) Patients whose APTT exceeded the upper limit of the institutional reference value in the APTT study up to the day before registration.
2) Patients who become pregnant before enrollment
3) Patients who are found to meet any of the exclusion criteria at the time of provisional registration by the time of registration.

Related Information

• Primary Sponsor: Matsumoto Tadashi