Efficacy and Safety of KBP-336 in Obese Individuals with Osteoarthritis

Официальное название

A Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of KBP-336 As an Adjunct to Diet and Exercise in Obese Individuals with Osteoarthritis of the Knee

Обзор

The goal of this clinical trial is to learn if KBP-336 works to treat pain in osteoarthritis in individuals living with obesity. It will also learn about the effects on other parameters, such as quality of life and metabolism, as well as safety of KBP-336. The main questions it aims to answer are: * Does KBP-336 lower knee pain from osteoarthritis in individuals with obesity * Does KBP-336 lower bodyweight in the same population. Researchers will compare KBP-336 to a placebo (a look-alike substance that contains no drug) to see if KBP-336 works to pain and obesity Participants will: * Take KBP-336 or a placebo every week for 6 months * Visit the clinic once every 2 weeks for checkups and tests * Keep a diary of their symptoms and the amount of medication they use in addition to KBP-336

Вмешательства

• Препарат KBP-336
  KBP-336 is a long acting Dual Amylin and Calcitonin Receptor agonist designed for weekly administration through subcutaneous injection.
• Препарат Placebo
  Placebo to match KBP-336

Первичные конечные точки

• The proportional change in body weight from baseline to endpoint [Срок оценки: 183 Days]
• The change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale from baseline to endpoint [Срок оценки: 183 Days]

Вторичные конечные точки (12)

• Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness and function scales during the trial and at Day 183 [Срок оценки: 183 Days]
• Proportion of subjects reaching ≥5, ≥10 or ≥15% weight loss from baseline at Day 183 [Срок оценки: 183 Days]
• Proportion of subjects reaching ≥30 and ≥50% reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale from baseline at Day 183 [Срок оценки: 183 Days]
• Change from baseline in Assessment of Quality of Life 8 Dimensions (AQol 8D) at Day 183 [Срок оценки: 183 Days]
• Change from baseline in Assessment of Quality of Life 8 Dimensions (AQol 8D) subscore Independent living at Day 183 [Срок оценки: 183 Days]
• Change from baseline in the weekly average of daily pain using the Numerical Rating Scale (NRS) during the trial, and at Day 183 [Срок оценки: 183 Days]
• Area under the curve from baseline in the weekly average of daily pain using the Numerical Rating Scale (NRS) to Day 183 [Срок оценки: 183 Days]
• Change from baseline to Day 183 in waist-to-hip ratio [Срок оценки: 183 Days]
• Change from baseline in whole body composition by DXA at Day 183 [Срок оценки: 183 Days]
• Change from baseline in bone mineral density of the lumber spine, femoral head, and total hip by DXA at Day 183 [Срок оценки: 183 Days]
• Change from baseline in Patient Global Assessment at Day 183 [Срок оценки: 183 Days]
• Outcome Measures in Rheumatology (OMERACT) - Osteoarthritis Research Society International (OARSI) responder rates at Day 183 [Срок оценки: 183 Days]

Критерии участия

Критерии включения

• The participant is able to read and understand the language and content of the study material and provide written Informed Consent.
• Willing and able to comply with study requirements and instructions
• 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
• 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) X-ray which fulfills the protocol specifications for reading
• Age ≥ 45 years of either sex
• Body Mass Index (BMI) ≥ 30 kg/m2
• 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.
• Intolerance or insufficient pain relief with standard of care (e.g. physiotherapy, paracetamol, local or systemic NSAID, short term opioid use, injections of hyaluronic acid, or corticosteroids) for symptomatic OA in the index knee in the opinion of the investigator.
• WOMAC pain subscale score in target knee at screening AND baseline ≥20 (0-50 scale)
• 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 Visit 13/ET (maximum 4000 mg paracetamol per day)

Критерии исключения

• Partial or complete joint replacement of either knee
• Target knee surgery or arthroscopy within 1 year prior to screening
• Diagnosis of OA resulting from trauma within the last 5 years
• Pain of the contralateral knee exceeding that of the target knee at the baseline visit, as measured by the WOMAC pain subscale
• Planned major surgery within the next 6 months
• Uncontrolled thyroid disease in the opinion of the Investigator based on medical history and laboratory results collected in screening
• Participant-reported weight loss >5% of body weight within the last 6 months of the screening visit
• Bariatric surgery within the last 12 months of the screening visit
• 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)
• 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)
• 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.
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at screening
• 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
• Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded.
• Participation in any previous DACRA/amylin study
• History or presence of clinically significant neurological disease or psychiatric disorder in the opinion of the investigator
• 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).
• Systemic corticosteroid treatment for the treatment of musculoskeletal conditions of more than 14 days during the past 6 months prior to screening.
• 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
• 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
• Vitamin D deficiency defined as blood 25-OH D3 concentration ≤25 nmol/L. Vitamin D supplementation and subsequent rescreening is allowed
• Presence or history of clinically significant allergies, including relevant drug hypersensitivity or allergy
• 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.
• History of alcohol or drug abuse within 5 years prior to screening, in the opinion of the Investigator.
• Use of an investigational drug within 90 days prior to screening
• For women of childbearing potential:

• Pregnancy (i.e. positive serum pregnancy test at screening) or breastfeeding
• Failure to agree to practice a highly effective method of contraception (see Appendix 2), from enrolment up to at least 3 months after the study end
• For sexually active men with a female partner of childbearing potential:

• Failure to agree to ensure that their female partners use a highly effective method of contraception (see Appendix 2) from enrolment up to at least 3 months after the study end
• Failure to agree not to donate sperm throughout the study and at least 3 months after the study end
• Unsuitable for study participation for any reason in the opinion of the Investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Чехия · 6 центров

• Pratia Brno, s.r.o — Brno
• L.K.N. Artrocentrum — Hlučín
• Medical Plus, s.r.o — Hradiště
• Pratia Pardubice a.s. — Pardubice
• Affidea Praha s.r.o — Prague
• Pratia Prague, s.r.o — Prague

Польша · 5 центров

• NZOZ Bif-Med. s.c. — Bytom
• Medyczne Centrum Hetmańska — Poznan
• DC-MED SP z o.o. — Swidnica
• NZOZ Lecznica MAK-MED s.c. — Warsaw
• Migre Polskie Centrum Leczenia Migreny — Wroclaw

Дания · 3 центра

• Sanos Clinic Nordjylland — Gandrup
• Sanos Clinic Herlev — Herlev
• Sanos Clinic Syddanmark — Vejle

Moldova · 3 центра

• IMSP Sptalul Clinic Municipal "Sfanta Treime" — Chisinau
• PMSI Cardiology Institute/RTL SM SRL — Chisinau
• Timofei Mosneaga Republican Clinical Hospital — Chisinau

Румыния · 2 центра

• Policlinica CCBR — Bucharest
• Quantum Medical Bucharest — Bucharest

Гонконг · 1 центр

• Hong Kong Center for Clinical Research — Гонконг

Идентификаторы

NCT: NCT06833749 · KBP-336-CD-003 · 2024-517264-27-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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