Clinical Study of Artz in the Treatment of Knee Osteoarthritis

Knee Osteoarthritis Clinical Trial

— Artz  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02826031
• Other study ID #: ARTZ2013PMS01
• Status: Recruiting
• Phase: Phase 4
• First received: June 27, 2016
• Last updated: May 3, 2017
• Start date: April 2016
• Est. completion date: December 2017

Study information

• Verified date: May 2017
• Source: Kunming Baker Norton Pharmaceutical Sales Co., Ltd.
• Contact: YA NAN TANG, Master
• Phone: +86-21-33278388
• Email: annie_tyn[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 If the knee pain has disappeared, this drug may be withdrawn.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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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,

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Sodium Hyaluronate Injection

• DICL-SR

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Nanfang Hospital	Guangzhou	Guangdong
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Peking Union Medical College Hospital	Peking	Beijing
China	Shanghai 6th People's Hospital	Shanghai	Shanghai
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Kunming Baker Norton Pharmaceutical Sales Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of all adverse events (AEs) and serious adverse events (SAEs)		up to 16 weeks
Primary	Compare the average daily doses (unit: pills) of the NSAID from Week9 (W9) to W12 between two groups		From W9 to W12 (4 weeks)
Secondary	Compare the average daily doses (unit: pills) of the NSAID from W5 to W8, and W5 to W12 between two groups		From W5 to W8 (4 weeks), and W5 to W12 (8 weeks)
Secondary	Compare the changes in the average daily doses (unit: pills) of the NSAID at the 8th and 12th week from baseline between two groups.		At the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
Secondary	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.		At the 8th week from baseline (1 week), and at the 12th week from baseline (1 week)
Secondary	Compare the days of NSAID consumption from W5 to W8, W9 to W12, and W5 to W12 between two groups.		From W5 to W8 (4 weeks), W9 to W12 (4 weeks), and W5 to W12 (8 weeks)
Secondary	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.		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)
Secondary	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.		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)