KBP-336 for Knee osteoarthritis | Obesity

Inclusion criteria

• {"criterion_text":"- The participant is able to read and understand the language and content of the study material and provide written Informed Consent\n- Willing to withdraw from any pain medication including, but not limited to, Opioids (including semisynthetic opioids), Non-Steroidal Anti-inflammatories (NSAIDs, with the exception of low-dose aspirin for thromboprophylaxis), COX-2 inhibitors, Topical medication, and Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs e.g. Duloxetine) and only use the allowed Rescue Medications from baseline to Visit11/ET (maximum 4000 mg paracetamol per day)\n- Willing and able to comply with study requirements and instructions\n- A diagnosis of OA of the target knee based on American College of Rheumatology (ACR) clinical and radiographic criteria(31), with OA symptoms (as reported by the participant) that have been present for at least 3 months prior to screening\n- Radiological OA grade 2 or 3 of the target knee, using the Kellgren-Lawrence method as graded by a central reader on a Fixed-Flexion X-ray obtained during screening, or on a recent (within 6 months) Xray which fulfills the protocol specifications for reading\n- Age ≥ 45 years of either sex\n- Body Mass Index (BMI) ≥ 30 kg/m2\n- Good health, defined as no significantly relevant medical history or findings on physical examination, vital signs, ECG, and laboratory results in the opinion of the investigator\n- Intolerance or insufficient pain relief with standard of care (e.g. physiotherapy, paracetamol, local or systemic NSAID, short term opioid use, injec-tions of hyaluronic acid, or corticosteroids) for symptomatic OA in the index knee in the opinion of the investigator.\n- WOMAC pain subscale score in target knee at screening AND baseline ≥20 (0-50 scale)"}

Exclusion criteria

• {"criterion_text":"- Partial or complete joint replacement of either knee\n- Conditions significantly affecting joint and bone health, in the opinion of the Investigator should be excluded (including but not limited to atrophic or hypotrophic OA, subchondral insufficiency fracture, osteonecrosis, osteoporotic fractures, excessive malalignment of the knee or severe chondrocalcinosis)\n- Active comorbid condition other than OA (e.g radicular back pain, bursitis, tendinitis) significantly affecting target knee pain reporting in the opinion of the investigator\n- A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at screening\n- History of gout, or pseudogout, with high likelihood of flare up during trial participation that would require NSAID treatment, in the opinion of the investigator\n- Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded\n- Participation in any previous DACRA/amylin study\n- History or presence of clinically significant neurological disease or psychiatric disorder in the opinion of the investigator\n- Intra-articular injection of corticosteroids within 3 months or hyaluronic acid within 6 months of screening in the target knee or into any other major joint within 30 days prior to screening (for extended-release corticosteroid injections: within 6 months in target knee and 3 months into any other major joint)\n- Systemic corticosteroid treatment for the treatment of musculoskeletal conditions of more than 14 days during the past 6 months prior to screening\n- Any pharmacological or non-pharmacological treatment primarily targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study\n- Target knee surgery or arthroscopy within 1 year prior to screening\n- Treatment with medication for obesity, including GLP-1 analogues, unless the dose of use has been stable for at least six months prior to screening\n- Vitamin D deficiency defined as blood 25-OH D3 concentration ≤25 nmol/L. Vitamin D supplementation and subsequent rescreening is allowed\n- Presence or history of clinically significant allergies, including relevant drug hypersensitivity or allergy\n- Current malignancy or treatment for malignancy within the past five years, apart from resected basal cell carcinoma, squamous skin cell carcinoma, or resected cervical atypia or carcinoma in situ, unless affecting the target knee area\n- History of alcohol or drug abuse within 5 years prior to screening, in the opinion of the Investigator\n- Use of an investigational drug within 90 days prior to screening\n- For women of childbearing potential: a. Pregnancy (i.e. positive serum pregnancy test at screening) or breastfeeding b. Failure to agree to practice a highly effective method of contraception (see Appendix A), from enrolment up to at least 3 months after the study end\n- For sexually active men with a female partner of childbearing potential: a. Failure to agree to ensure that their female partners use a highly effective method of contraception (see Appendix A) from enrolment up to at least 3 months after the study end b. Failure to agree not to donate sperm throughout the study and at least 3 months after the study end\n- Unsuitable for study participation for any reason in the opinion of the Investigator\n- Diagnosis of OA resulting from trauma within the last 5 years\n- Pain of the contralateral knee exceeding that of the target knee at the baseline visit, as measured by the WOMAC pain subscale\n- Planned major surgery within the next 6 months\n- Uncontrolled thyroid disease in the opinion of the Investigator based on medical history and laboratory results collected in screening\n- Participant-reported weight loss >5% of body weight within the last 6 months of the screening visit\n- Bariatric surgery within the last 12 months of the screening visit\n- Current comorbid condition, other than OA, affecting target knee or systemic illness known to be significantly associated with arthritis or joint pathology affecting any joint, including but not necessarily limited to endocrinopathies, inflammatory, or autoimmune disease with significant joint involvement (e.g., Rheumatoid Arthritis); Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis)"}

Primary endpoints

• {"endpoint_text":"- The proportional change from baseline in body weight at Day 183","definition_or_measurement_approach":"Proportional change from baseline in measured body weight at Day 183 compared to baseline."}
• {"endpoint_text":"- OR The change from baseline in the WOMAC pain scale at Day 183","definition_or_measurement_approach":"Change from baseline in the WOMAC pain subscale score at Day 183 compared to baseline."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in WOMAC pain scale during the trial","definition_or_measurement_approach":"Change from baseline in WOMAC pain subscale measured during the trial."}
• {"endpoint_text":"- Change from baseline in WOMAC total score, WOMAC stiffness and WOMAC function scales during the trial and at Day 183","definition_or_measurement_approach":"Change from baseline in total WOMAC score and WOMAC subscales measured during the trial and at Day 183."}
• {"endpoint_text":"- Proportion of subjects reaching ≥5, ≥10 or ≥15% weight loss from baseline at Day 183.","definition_or_measurement_approach":"Proportion of participants achieving specified percent reductions in body weight from baseline at Day 183."}
• {"endpoint_text":"- Proportion of subjects reaching ≥30 and ≥50% reduction in WOMAC pain scale from baseline at Day 183.","definition_or_measurement_approach":"Proportion of participants achieving ≥30% and ≥50% reduction in WOMAC pain subscale from baseline at Day 183."}
• {"endpoint_text":"- Change from baseline in AQol 8D at Day 183","definition_or_measurement_approach":"Change from baseline in AQoL-8D quality of life score at Day 183."}
• {"endpoint_text":"- Change from baseline in AQol 8D subscore Independent living at Day 183","definition_or_measurement_approach":"Change from baseline in the Independent living subscore of AQoL-8D at Day 183."}
• {"endpoint_text":"- Change from baseline in the weekly average of daily pain during the trial, and at Day 183","definition_or_measurement_approach":"Change from baseline in weekly average of daily pain (patient-reported) during trial and at Day 183."}
• {"endpoint_text":"- Area under the curve from baseline in the weekly average of daily pain to Day 183","definition_or_measurement_approach":"Area under the curve (AUC) of weekly average daily pain from baseline to Day 183."}
• {"endpoint_text":"- Change from baseline to Day 183 in waist-to-hip ratio","definition_or_measurement_approach":"Change from baseline in measured waist-to-hip ratio at Day 183."}
• {"endpoint_text":"- Change from baseline in whole body composition by DXA at Day 183","definition_or_measurement_approach":"Change from baseline in whole body composition parameters assessed by DXA at Day 183."}
• {"endpoint_text":"- Change from baseline in bone mineral density of the lumber spine, femoral head, and total hip by DXA at Day 183","definition_or_measurement_approach":"Change from baseline in bone mineral density at specified sites assessed by DXA at Day 183."}
• {"endpoint_text":"- Change from baseline in PGA at Day 183","definition_or_measurement_approach":"Change from baseline in Patient Global Assessment (PGA) score at Day 183."}
• {"endpoint_text":"- OMERACT-OARSI responder rates at Day 183","definition_or_measurement_approach":"OMERACT-OARSI responder rates defined per OMERACT-OARSI criteria at Day 183."}
• {"endpoint_text":"- Average weekly days using rescue medication","definition_or_measurement_approach":"Average number of days per week the participant used permitted rescue medication during the trial."}
• {"endpoint_text":"- Change from baseline in ICOAP at Day 183","definition_or_measurement_approach":"Change from baseline in ICOAP (Intermittent and Constant Osteoarthritis Pain) score at Day 183."}

Methods

• Social media (SnMe) - documented recruitment material files named K2_Recruitment material_SnMe and country-specific variants indicate social media recruitment in Denmark, Poland and Czechia.
• Newspaper - Czechia (document: K2_Recruitment material_Pratia Newspaper_CZ).
• Website / online form - Czechia (document: K2_Recruitment material_Pratia Website form_CZ).
• Clinic-based recruitment / local clinic materials - Romania (documents: K2_Recruitment Material_Policlinica CCBR and Quantum Medical_RO) and site-specific recruitment materials in other countries.

Denmark

Earliest CTIS Part Ii Submission Date

08-11-2024

Latest Decision Or Authorization Date

03-12-2024

Processing Time Days

25

Number Of Sites

3

Number Of Participants

300

Czechia

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

30-04-2025

Processing Time Days

33

Number Of Sites

6

Number Of Participants

100

Romania

Earliest CTIS Part Ii Submission Date

24-03-2025

Latest Decision Or Authorization Date

06-05-2025

Processing Time Days

43

Number Of Sites

2

Number Of Participants

45

Poland

Earliest CTIS Part Ii Submission Date

10-04-2025

Latest Decision Or Authorization Date

04-05-2025

Processing Time Days

24

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

KeyBioscience S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Medpace Reference Laboratories LLC

Responsibilities

Pharmacokinetic analysis

Name

NBCD A/S

Name

Nordic Bioscience A/S

Third parties

• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"Pharmacokinetic analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Denmark","full_name":"NBCD A/S","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"","organisation_type":"Pharmaceutical company"}