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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

KeyBioscience S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

13 Dec 2024 → ongoing

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of multiple doses of KBP-336 compared to placebo on body weight, and pain due to knee OA.

Secondary objectives 4

1. To evaluate the efficacy of multiple doses of KBP-336 compared to placebo on other symptoms of OA
2. To evaluate the efficacy of multiple doses of KBP-336 compared to placebo on Quality of Life
3. To evaluate the overall safety of KBP-336 (multiple doses) compared to placebo
4. To evaluate changes in DXA assessments of lean, fat and bone mass compared to placebo

Conditions and MedDRA coding

Knee osteoarthritis

Regulatory references

Scientific advice from competent authorities

Danish Medicines Agency

Plan to share IPD

Yes

IPD plan description

Data obtained through this study may be provided to qualified researchers on request in accordance with international principles for responsible research (under the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA)). Approval of the request (including e.g. research proposal and statistical analysis plan) and execution of all applicable agreements (i.e. a data sharing agreement) are prerequisites to the sharing of data with the requesting party. Data will only be shared in encoded form to protect participant identity and with requirements for data protection as well as requirements against unauthorized use and disclosure. Participant identity will remain confidential. Participants can inquire about data transfers and security measures at any time by contacting the trial physician.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. The participant is able to read and understand the language and content of the study material and provide written Informed Consent
2. Willing and able to comply with study requirements and instructions
3. 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
4. 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
5. Age ≥ 45 years of either sex
6. Body Mass Index (BMI) ≥ 30 kg/m2
7. 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
8. 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.
9. WOMAC pain subscale score in target knee at screening AND baseline ≥20 (0-50 scale)
10. 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)

Exclusion criteria 28

1. Partial or complete joint replacement of either knee
2. Target knee surgery or arthroscopy within 1 year prior to screening
3. Diagnosis of OA resulting from trauma within the last 5 years
4. Pain of the contralateral knee exceeding that of the target knee at the baseline visit, as measured by the WOMAC pain subscale
5. Planned major surgery within the next 6 months
6. Uncontrolled thyroid disease in the opinion of the Investigator based on medical history and laboratory results collected in screening
7. Participant-reported weight loss >5% of body weight within the last 6 months of the screening visit
8. Bariatric surgery within the last 12 months of the screening visit
9. 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)
10. 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)
11. 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
12. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at screening
13. 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
14. Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded
15. Participation in any previous DACRA/amylin study
16. History or presence of clinically significant neurological disease or psychiatric disorder in the opinion of the investigator
17. 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)
18. Systemic corticosteroid treatment for the treatment of musculoskeletal conditions of more than 14 days during the past 6 months prior to screening
19. 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
20. 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
21. Vitamin D deficiency defined as blood 25-OH D3 concentration ≤25 nmol/L. Vitamin D supplementation and subsequent rescreening is allowed
22. Presence or history of clinically significant allergies, including relevant drug hypersensitivity or allergy
23. 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
24. History of alcohol or drug abuse within 5 years prior to screening, in the opinion of the Investigator
25. Use of an investigational drug within 90 days prior to screening
26. 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
27. 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
28. Unsuitable for study participation for any reason in the opinion of the Investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The proportional change from baseline in body weight at Day 183
2. OR The change from baseline in the WOMAC pain scale at Day 183

Secondary endpoints 15

1. Change from baseline in WOMAC pain scale during the trial
2. Change from baseline in WOMAC total score, WOMAC stiffness and WOMAC function scales during the trial and at Day 183
3. Proportion of subjects reaching ≥5, ≥10 or ≥15% weight loss from baseline at Day 183.
4. Proportion of subjects reaching ≥30 and ≥50% reduction in WOMAC pain scale from baseline at Day 183.
5. Change from baseline in AQol 8D at Day 183
6. Change from baseline in AQol 8D subscore Independent living at Day 183
7. Change from baseline in the weekly average of daily pain during the trial, and at Day 183
8. Area under the curve from baseline in the weekly average of daily pain to Day 183
9. Change from baseline to Day 183 in waist-to-hip ratio
10. Change from baseline in whole body composition by DXA at Day 183
11. Change from baseline in bone mineral density of the lumber spine, femoral head, and total hip by DXA at Day 183
12. Change from baseline in PGA at Day 183
13. OMERACT-OARSI responder rates at Day 183
14. Average weekly days using rescue medication
15. Change from baseline in ICOAP at Day 183

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

KeyBioscience S.A.

Sponsor organisation

KeyBioscience S.A.

Address

Via Francesco Soave 6

City

Lugano

Postcode

6900

Country

Switzerland

Scientific contact point

Organisation

KeyBioscience S.A.

Contact name

Nordic Bioscience Endocrinology dept.

Public contact point

Organisation

KeyBioscience S.A.

Contact name

Nordic Bioscience Endocrinology dept.

Third parties 3

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 83 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications