Clinical trial NCT02826031: Clinical Study of Artz in the Treatment of Knee Osteoarthritis
Official title: A Multi-center, Randomized, Open-label, Parallel-arm Controlled Study Comparing Demand-based Monotherapy of Non-steroidal Anti-inflammatory Drug (NSAID) vs. Demand-based NSAID Combined With Sodium Hyaluronate Injection in the Treatment of Chinese Patients With Mild to Moderate Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Knee Osteoarthritis
Keywords: Sodium Hyaluronate
mild to moderate knee osteoarthritis
Lead sponsor: Kunming Baker Norton Pharmaceutical Sales Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-07-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, open-label, parallel-arm phase IV clinical study, for which a total of 300 patients with mild to moderate knee osteoarthritis will be enrolled. In the first 4 weeks (run-in period), the subjects will receive on-demand treatment with Diclofenac Sodium Sustained Release Tablets (DICL-SR) 75mg, quaque die（QD）. After the run-in period, the subjects, if their knee pain has not worsened to a level requiring surgical treatment, will be randomized to two groups in 1:1 ratio: one group receiving Artz® via intra-articular injection (once weekly, for 5 consecutive weeks) in combination with DICL-SR 75mg,quaque die（QD）, for 12 consecutive weeks on demand. The other group receiving DICL-SR 75mg alone,quaque die（QD）, for 12 consecutive weeks on demand. DICL-SR 75mg quaque die（QD） may be administered to the subjects of both groups on demand as long as they have a knee pain. If the knee pain has disappeared, this drug may be withdrawn. However, if the pain occurs again and requires treatment, oral administration of DICL-SR may be resumed. A subject is allowed to withdraw from this study prematurely if unable to tolerate the adverse effects.

A total of 8 visits have been scheduled for this study, including Visit 1/screening period (Week -4), Visit 2/baseline (Week 0), Visit 3 (Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), Visit 7 (Week 8) and Visit 8 (Week 12).

A total of 300 subjects will participate in this study at 6 to 8 centers in China, and patient enrollment is expected to take up to 12 months.


Eligibility criteria: Inclusion Criteria:

1. Adult Chinese subjects, at age≥18, either gender, diagnosed with osteoarthritis of the target knee and Kellgren-Lawrence (KL) classification Grade 1\~3, as evidenced by X-ray examination in the last 3 months (mild to moderate narrowing of joint space and / or marked osteophytes of tibiofemoral joint space)
2. Persist pain of the target knee after exercise, weight loss and physical therapy;
3. A baseline WOMAC A1 score for the target knee rated at 40-90mm (moderate to severe walk-associated pain) on 100mm Visual analogue scale(VAS); Able to understand and sign the Informed Consent Form (ICF) that has already been approved by the Independent Ethics Committee (IEC) Note: the informed consent may also be given by the duly authorized representative of the subject.

Exclusion Criteria:

1. A diagnosis of bilateral knee osteoarthritis;
2. Clinically significant (requiring surgery) valgus or varus deformity of the knee joint, ligamentous laxity or unstable meniscus;
3. Complicated by inflammation or any other disease /condition (e.g., rheumatic arthritis, metabolic bone disease, psoriasis, gout, pseudogout, chondrocalcinosis, etc.) that may affect the knee joint;
4. A history of septicemia, clinically considered sub-acute infection of the target knee joint;
5. A history of surgery on the target knee (in the last 6 months);
6. A history of asthma, urticaria or allergy after use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs);
7. Severe hepatic or renal disease or hepatic /renal failure;
8. Any unscheduled surgery on the lower limb;
9. Clinically significant lower venous or lymphatic obstruction;
10. Clinically significant obvious exudation or inflammation of the target knee;
11. Skin disorders or infection at the injection site;
12. Pregnant or lactating women;
13. Known allergy to guanylin and / or any active ingredient or excipient of hyaluronic acid-based injection / diclofenac sodium;
14. Treatment with any hyaluronic acid (HA) or its derivatives for the target knee within six months before this trial;
15. Intra-articular (IA) injection of steroids into the target knee within 3 months before this trial;
16. Presence of any contraindication to IA injection, e.g., patients who are receiving anti-coagulation therapy or clinically have potential coagulation disorders (e.g., hepatic disease);
17. Presence of any clinically significant disease (e.g., significant mental or nervous disorders, alcohol/drug abuse), unstable/poorly controlled diseases, or other factors, which may affect their evaluation or participation in this study in the investigator's judgment
18. Perioperative pain associated with coronary artery bypass surgery (CABG);
19. A history of gastrointestinal bleeding or perforation following use of NSAIDs;
20. Presence of active gastrointestinal ulcer /bleeding, or a past history of recurrent ulcer/bleeding; Chief complaint complicated by pain beyond the target knee,

Primary outcomes:
measure: Compare the average daily doses (unit: pills) of the NSAID from Week9 (W9) to W12 between two groups
timeFrame: From W9 to W12 (4 weeks)
Secondary outcomes:
measure: Compare the average daily doses (unit: pills) of the NSAID from W5 to W8, and W5 to W12 between two groups
timeFrame: From W5 to W8 (4 weeks), and W5 to W12 (8 weeks)
measure: Compare the changes in the average daily doses (unit: pills) of the NSAID at the 8th and 12th week from baseline between two groups.
timeFrame: At the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
measure: Compare the percentage changes in the average daily doses (unit: pills) of the NSAID at the 8th and 12th week from baseline between two groups.
timeFrame: At the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
measure: Compare the days of NSAID consumption from W5 to W8, W9 to W12, and W5 to W12 between two groups.
timeFrame: From W5 to W8 (4 weeks), W9 to W12 (4 weeks), and W5 to W12 (8 weeks)
measure: Compare the changes in WOMAC A1 score (walk-associated pain), WOMAC A, B and C score and patient global assessment (PTGA) at the 4th, 8th and 12th week from baseline between two groups.
timeFrame: At the 4th week from baseline (1 week), at the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
measure: Compare the changes in clinical observer global assessment (COGA), and scores for activities of daily living (ADL) at the 4th, 8th and 12th week from baseline between two groups.
timeFrame: At the 4th week from baseline (1 week), at the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
Other outcomes:
measure: Incidence of all adverse events (AEs) and serious adverse events (SAEs)
timeFrame: up to 16 weeks
Locations:
city: Peking
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Shanghai 6th People's Hospital
state: Shanghai
Study officials:
affiliation: Second Affiliated Hospital of Xi'an Jiaotong University
name: Kun Zheng WANG, Doctor
role: STUDY_CHAIR
References: