Knee Osteoarthritis, Obesity
Conditions
Keywords
Ecnoglutide, KOA, Obesity
Brief summary
The main purpose of the study is to evaluate the efficacy and safety of ecnoglutide injections versus placebo in obese participants with KOA.
Detailed description
In this Phase III study, eligible participants will be randomized into one of the two cohorts in a 1:1 ratio to receive once-weekly subcutaneous ecnoglutide injection or placebo, including a dose-escalation period, with the total treatment duration of up to 68 weeks, plus 5 weeks of follow-up period. The overall study will last for 73 weeks.
Interventions
DRUGEcnoglutide Injection
subcutaneous injection
subcutaneous injection
Sponsors
Hangzhou Sciwind Biosciences Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Body mass index (BMI) ≥ 28.0 kg/m\^2; 2. The target knee must meet the diagnostic criteria of American College of Rheumatology (ACR) for knee osteoarthritis (clinical and radiological), with moderate radiographic changes (Kellgren-Lawrence grade 2 or 3). The target knee is defined as the knee with the most symptomatic knee at screening period; if pain in both knees are equal, the target knee will be the most dominant leg (preferred leg); 3. Prior to screening, target knee pain lasting more than 12 weeks, and according to participant's self-report or medical history at screening, target knee pain lasting more than 15 days in the past month; 4. At screening and prior to randomization, WOMAC pain score (NRS 0-10) of the target knee must be between 4 and 9 (to avoid bias in reporting, participants must not be informed of the pain score used to determine eligibility for the study); 5. Self-reported by the participant who has a history of unsuccessful weight loss attempt by diet and exercise.
Exclusion criteria
1. The target knee has undergone joint replacement surgery; 2. The target knee has undergone arthroscopy within 12 months prior to screening; 3. At the time of screening, the target knee joint has any clinical features and symptoms of other active infections or crystal-induced arthropathies, as well as any other active joint diseases that may interfere with assessment; 4. The target knee has received intra-articular injections of hyaluronic acid, any other investigational drugs, or biologics within 3 months prior to screening; or has undergone any procedures that result in persistent sensory loss in the target knee (e.g., ablation) within 6 months prior to screening; 5. Has received any intramuscular or oral corticosteroids (investigational or marketed) within 30 days prior to screening, or has received any intra-articular corticosteroid injections (investigational or marketed) in any joint within 90 days prior to screening; 6. History of joint instability in either knee within 12 months prior to screening, such as anterior cruciate ligament rupture or recent trauma; 7. History of any other potentially causative and/or confounding diseases, including Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease-associated arthritis, sarcoidosis, amyloidosis, or fibromyalgia; 8. Presence of symptomatic hip osteoarthritis at the time of screening, with the exception of those who have undergone hip replacement surgery; 9. Conditions that may interfere with the assessment of target knee pain during screening include, but are not limited to: * Pain in any part of the lower limb or back equal to or more severe than the pain in the target knee; * Pain radiating to the knee from other areas, such as hip pain affecting the knee or radicular pain; * Chronic widespread pain (including neuropathic pain); 10. Change of body weight \>5% within 3 months prior to screening (selfreported); 11. Diagnosis of diabetes (excluding gestational diabetes), or with a history of diabetic ketoacidosis or hyperosmolar state/coma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | Baseline, week 68 |
| Percentage Change in Body Weight | Baseline, week 68 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with ≥50% of Reduction in WOMAC Physical Function Subscale Score | Baseline, week 68 | — |
| Change in SF36V2 Score | Baseline, week 68 | — |
| Change in PGI-S Pain and Function Score of the Target Knee Joint | Baseline, week 68 | PGI-S stands for Patient Global Impressions Scale - Severity |
| Change in PGI-C Pain and Function Score of the Target Knee Joint | Baseline, week 68 | PGI-C stands for Patient Global Impressions Scale - Change |
| Change in Body Mass Index (BMI) | Baseline, week 68 | — |
| Change in Walking Distance During the 6-minute Walk Test | Baseline, week 68 | — |
| Percentage of Participants Using Allowed Analgesics During Wash Out | Baseline, week 68 | — |
| Amount of Allowed Analgesics Used During Wash Out | Baseline, week 68 | Amount of allowed analgesics used during wash out at end of treatment (week 68)is presented. Allowed analgesic during washout should be taken within 72 hour before the visit and prior to WOMAC assessment. |
| Percentage of Participants Using Analgesics | Baseline, week 68 | — |
| Change in Amount of Analgesics Used | Baseline, week 68 | — |
| Change in Lipid Profile | Baseline, week 68 | Include triglicerides, LDL-C, HDL-C, total cholesterol |
| Change in Fasting Plasma Glucose (FPG) | Baseline, week 68 | — |
| Change in HbA1c | Baseline, week 68 | — |
| Change in Fasting Insulin | Baseline, week 68 | — |
| Change in Fasting C-peptide | Baseline, week 68 | — |
| Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Baseline, week 68 | — |
| Change in Blood Pressure | Baseline, week 68 | — |
| Adverse events | Week 1 to week 73 (EOS) | — |
| Change in Patient Health Questionnaire-9 (PHQ-9) Score | Baseline to week 73 (EOS) | PHQ-9 questionnaire will be used to monitor status of mental health of the participants. |
| Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline to week 73 (EOS) | C-SSRS questionnaire will be used to monitor status of mental health of the participants. |
| Change in Waist Circumference | Baseline, week 68 | — |
| Change in Hip Circumference | Baseline, week 68 | — |
| Change in Waist-to-hip Ratio | Baseline, week 68 | — |
| Trough Concentration of Ecnoglutide | Week 1 to week 73 (EOS) | — |
| Percentage of Participants with ≥5% of Body Weight Loss | Baseline, week 68 | — |
| Percentage of Participants with ≥10% of Body Weight Loss | Baseline, week 68 | — |
| Percentage of Participants with ≥50% of Reduction in WOMAC Pain Subscale Score | Baseline, week 68 | — |
| Change in WOMAC Physical Function Subscale Score | Baseline, week 68 | — |
| Change in Short Form 36 (SF36) V2 Physical Function Subscale Score | Baseline, week 68 | — |
| Percentage of Participants with ≥15% of Body Weight Loss | Baseline, week 68 | — |
| Absolute Change in Body Weight | Baseline, week 68 | — |
| Change in WOMAC Total Score | Baseline, week 68 | — |
Countries
China
Contacts
CONTACTYao Li
PRINCIPAL_INVESTIGATORWeihua XU
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed