NCT02826031

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 If the knee pain has disappeared, this drug may be withdrawn.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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for phase_4 knee-osteoarthritis

Timeline
Completed

Started Apr 2016

Geographic Reach
1 country

6 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2016

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 27, 2016

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 7, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

May 4, 2017

Status Verified

May 1, 2017

Enrollment Period

1.5 years

First QC Date

June 27, 2016

Last Update Submit

May 3, 2017

Conditions

Knee Osteoarthritis

Keywords

Sodium Hyaluronatemild to moderate knee osteoarthritis

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • +1 more secondary outcomes

Other Outcomes (1)

  • Incidence of all adverse events (AEs) and serious adverse events (SAEs)

    up to 16 weeks

Study Arms (2)

Sodium Hyaluronate Injection + DICL-SR

EXPERIMENTAL

Each syringe (2.5mL) contains 25mg of sodium hyaluronate, and one Artz® will be administered via intra-articular injection into the target knee at the baseline and Weeks 1, 2, 3 and 4 respectively for the combination group. From the run-in period to the end of study, both groups will receive DICL-SR 75mg, which is administered on demand for treatment of knee pain. If the knee pain is relieved or has disappeared, DICL-SR may be withdrawn. However, if the pain occurs again and requires treatment, the drug may be resumed. If a dose of 75mg daily fails to control the knee pain, it may be increased to the maximum dose 150mg daily upon the approval of the investigator, that is, 75mg bis in die（BID） daily

Drug: Sodium Hyaluronate InjectionDrug: DICL-SR

DICL-SR

ACTIVE COMPARATOR

From the run-in period to the end of study, both groups will receive Diclofenac Sodium Sustained-release Tablets(DICL-SR) 75mg, which is administered on demand for treatment of knee pain. If the knee pain is relieved or has disappeared, DICL-SR may be withdrawn. However, if the pain occurs again and requires treatment, the drug may be resumed. If a dose of 75mg daily fails to control the knee pain, it may be increased to the maximum dose 150mg daily upon the approval of the investigator, that is, 75mg bis in die（BID daily）. A subject is allowed to withdraw from this study prematurely if unable to tolerate the adverse effects.

Drug: DICL-SR

Interventions

Sodium Hyaluronate InjectionDRUG
Sodium Hyaluronate Injection + DICL-SR
DICL-SRDRUG
DICL-SRSodium Hyaluronate Injection + DICL-SR

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • Persist pain of the target knee after exercise, weight loss and physical therapy;
  • 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.

You may not qualify if:

  • A diagnosis of bilateral knee osteoarthritis;
  • Clinically significant (requiring surgery) valgus or varus deformity of the knee joint, ligamentous laxity or unstable meniscus;
  • 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;
  • A history of septicemia, clinically considered sub-acute infection of the target knee joint;
  • A history of surgery on the target knee (in the last 6 months);
  • A history of asthma, urticaria or allergy after use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs);
  • Severe hepatic or renal disease or hepatic /renal failure;
  • Any unscheduled surgery on the lower limb;
  • Clinically significant lower venous or lymphatic obstruction;
  • Clinically significant obvious exudation or inflammation of the target knee;
  • Skin disorders or infection at the injection site;
  • Pregnant or lactating women;
  • Known allergy to guanylin and / or any active ingredient or excipient of hyaluronic acid-based injection / diclofenac sodium;
  • Treatment with any hyaluronic acid (HA) or its derivatives for the target knee within six months before this trial;
  • Intra-articular (IA) injection of steroids into the target knee within 3 months before this trial;
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

ACTIVE NOT RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

NOT YET RECRUITING

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

NOT YET RECRUITING

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 409099, China

RECRUITING

Shanghai 6th People's Hospital

Shanghai, Shanghai Municipality, 200235, China

NOT YET RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Hyaluronic Acid

Condition Hierarchy (Ancestors)

OsteoarthritisArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic Diseases

Intervention Hierarchy (Ancestors)

GlycosaminoglycansPolysaccharidesCarbohydrates

Study Officials

  • Kun Zheng WANG, Doctor

    Second Affiliated Hospital of Xi'an Jiaotong University

    STUDY CHAIR

Central Study Contacts

YA NAN TANG, Master

CONTACT

+86-21-33278388annie_tyn@163.com

Kun Zheng WANG, Doctor

CONTACT

+86-29-87678326wkzh1955@163.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2016

First Posted

July 7, 2016

Study Start

April 1, 2016

Primary Completion

October 1, 2017

Study Completion

December 1, 2017

Last Updated

May 4, 2017

Record last verified: 2017-05

Locations

CN(6)