E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic osteoarthritis of the knee with Kellgren-Lawrence grade II and III |
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E.1.1.1 | Medical condition in easily understood language |
Symptomatic osteoarthritis of the knee with Kellgren-Lawrence grade II and III |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that treatment with JTA-004 leads to a reduction in knee pain intensity with respect to placebo in subjects suffering from symptomatic OA of the knee at Month 3. |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives
To demonstrate that treatment with JTA-004 leads to a reduction in knee pain intensity with respect to placebo at Month 6
To demonstrate that reduction in knee pain intensity with JTA-004 is non inferior to reduction in knee pain intensity with active comparator at Month3
To demonstrate that treatment with JTA-004 leads to an improvement in knee physical function with respect to placebo at Month 3
To demonstrate that treatment with JTA-004 leads to an improvement in Patient Global Assessment with respect to placebo at Month 3
To demonstrate that treatment with JTA-004 leads to an improvement in knee physical function with respect to placebo at Month 6
To demonstrate that treatment with JTA-004 leads to an improvement in subject global health and well-being with respect to placebo at Month 3
To demonstrate that treatment with JTA-004 leads to a higher rate of responders (defined as ≥ 30% pain intensity reduction) with respect to placebo at Month 3 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must satisfy ALL the following criteria to be included in the study:
1. Male/female aged above 40 years
2. Ambulatory (able to walk unassisted, the use of a crutch or a walking stick (only one) is allowed if already used at screening but should be avoided during the study up to the 6-month follow-up visit)
3. Diagnosed with primary knee OA, fulfilling the following American College of Rheumatology (ACR) criteria at the target knee:
• Pain present for most days of the preceding month
• Morning stiffness < 30 minutes
• Kellgren-Lawrence grade II or III (confirmed by appropriate X-rays taken within 6 months prior to screening Visit)
4. Target knee pain ≥ 200 mm and ≤ 400 mm out of 0-500 mm on the WOMAC ® VA3.1 pain questionnaire (sum of 5 questions) at screening and baseline
5. Insufficient/failed response or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs (NSAIDs) as reported by the subject
6. Willing and able to abstain from initiation of physical therapy and knee braces at the target knee up to the 6-month follow up visit (a subject undergoing physical therapy or using knee braces at a stable frequency for at least 2 weeks prior to screening is allowed to continue at same frequency (frequency increase is not allowed)
7. Capable to understand and comply with study requirements and to provide a written, dated, and signed informed consent prior to any study procedure for participation in the study and transmission of personal "pseudo-anonymized" data
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E.4 | Principal exclusion criteria |
Current symptoms and/or signs related to the disease under study:
1. History of trauma or surgery or arthroscopy at the target knee within 12 months before inclusion
2. Concomitant inflammatory disease or other conditions affecting the joints (e.g., infectious arthritis, rheumatoid arthritis, psoriatic arthritis or spondyloarthropathy, Paget’s disease, hemochromatosis…)
3. Any target knee abnormality that could impact safety or efficacy assessment.
4. Microcrystalline arthropathies: chondrocalcinosis/calcium pyrophosphate dihydrate disease (pseudo-gout) or gout if believed likely to interfere with the study endpoints, in the opinion of the Investigator
5. Clinically significant valgus/varus deformities at the Investigator’s discretion
6. Any musculoskeletal condition (such as symptomatic hip osteoarthritis, amputation, neurologic disorder, chronic back pain with or without radiculopathy, sciatica) that would impede measurement of efficacy at target knee
7. Contralateral knee pain equal to or exceeding the pain in the target knee (on the WOMAC ® VA3.1 pain questionnaire) at screening and/or baseline
8. Knee arthroplasty planned within 12 months after the screening visit
Current or previous diagnoses, signs and/or symptoms:
9. Uncontrolled diabetes mellitus (hemoglobin A1c [HbA1c] > 10% or > 86 mmol/mol), end-stage hepatic or renal disease (severe and clinically significant abnormalities according to local laboratory ranges) documented in the subject’s file
10. Any relevant cardiovascular disease (severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease) or any clinically significant electrocardiogram (ECG) abnormality as judged by the Investigator
11. Subject with neuropathic pain or chronic pain syndrome including fibromyalgia
12. Current (or within the last 5 years prior to entering the study) history of solid or hematological neoplasia or bone marrow transplantation (except for basal cell carcinoma and completely excised squamous cell carcinoma)
13. Other severe acute or chronic medical or psychiatric conditions or pre-dispositions or laboratory abnormalities, as judged by the Investigator
14. Current or past history of coagulation disorders (according to local laboratory ranges), as judged by the Investigator
15. Hypersensitivity to any components of hyaluronic acid (HA)-based injection products
16. Hypersensitivity to human biological material including blood and blood derived products, potential excipients and residues from manufacturing process, documented clinically or by laboratory tests
17. Hypersensitivity to avian proteins
Current or previous treatment:
18. Participation in another clinical trial within 3 months prior to screening (within 1 year prior to screening if disease-modifying OA drug [DMOAD] received and if the Investigator considers it could impact the safety or efficacy assessment)
19. Subject previously treated with JTA-004 within 2 years prior to screening
20. Subject treated with intra-articular viscosupplement or blood-derived product (e.g., platelet-rich plasma) injection in the target knee within 6 months prior to screening
21. Subject treated with intra-articular glucocorticoid injection in the target knee within 4 months prior to screening
22. Started the use of slow acting drugs for OA such as glucosamine, glucosamine sulfate, chondroitin sulfate, diacerein, curcumin, soybean/avocado extracts or related products within 1 months prior to screening
23. Current chemo-, radio- or immuno-cancer-therapy or immunosuppressive therapy
24. Chronic (≥ 3 days/week within the last 3 months) use of opioids other than weak opioids (codeine, dihydrocodeine, tramadol…)
25. Chronic (> 15 consecutive days) use of steroids
Safety aspects concerning female subjects of childbearing potential:
26. Breast-feeding
27. Pregnancy
28. Woman with positive urine pregnancy test
29. Woman not willing or not able to use a highly effective contraceptive method during the 6-month active follow-up period. Highly effective birth control methods are:
a) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
b) Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
c) Intrauterine device
d) Intrauterine hormone-releasing system
e) Bilateral tubal occlusion
Other exclusion criteria:
30. Body Mass Index (BMI) of 40 kg/m2 or greater at baseline
31. Signs of an active drug or alcohol dependence, serious current illness, mental illness or any other factors which may interfere with subject’s ability to understand and comply with study requirements, as judged by the Investigator.
32. Life expectancy less than 12 months at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the difference between JTA-004 and placebo in mean change from baseline in knee pain at Month 3 using the Western Ontario McMaster University (WOMAC®) VA3.1 pain subscale (subscale A). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints:
a) Key secondary endpoints:
- Difference between JTA-004 and placebo in mean change from baseline in knee pain at Month 6 using the WOMAC® VA3.1 pain subscale (subscale A)
- Difference between JTA-004 and active comparator in mean change from baseline in knee pain at Month 3 using the WOMAC® VA3.1 pain subscale (subscale A)
- Difference between JTA-004 and placebo in mean change from baseline in knee physical function at Month 3 using the WOMAC® VA3.1 physical function subscale (subscale C)
- Difference between JTA-004 and placebo in mean change from baseline in PGA at Month 3
- Difference between JTA-004 and placebo in mean change from baseline in knee physical function at Month 6 using the WOMAC® VA3.1 physical function subscale (subscale C)
- Difference between JTA-004 and placebo in mean change from baseline in subject global health and well-being score at Month 3 using the EQ-5D-5L questionnaire
- Difference between JTA-004 and placebo in responder rate (defined as ≥ 30% pain intensity reduction) at Month 3
b) Other secondary endpoints:
- Difference between JTA-004 and placebo in mean change from baseline in knee pain at Month 1 using the WOMAC® VA3.1 pain subscale (subscale A)
- Difference between JTA-004 and placebo in mean change from baseline in knee stiffness at each follow-up visit using the WOMAC® VA3.1 stiffness subscale (subscale B)
- Difference between JTA-004 and placebo in mean change from baseline in knee physical function at Month 1 using the WOMAC® VA3.1 physical function subscale (subscale C)
- Difference between JTA-004 and placebo in mean change from baseline in PGA at Month 1 and at Month 6 - Difference between JTA-004 and placebo in mean change from baseline in IGA at each follow-up visit
- Difference between JTA-004 and placebo in mean change from baseline in subject global health and well-being score at Month 1 and at Month 6 using the EQ-5D-5L questionnaire
- Difference between JTA-004 and placebo in the mean daily consumption of rescue medications over 6 months
- Difference between JTA-004 and active comparator in mean change from baseline in knee pain at each follow-up visit using the WOMAC® VA3.1 pain subscale (subscale A)
- Difference between JTA-004 and active comparator in mean change from baseline in knee stiffness at each follow-up visit using the WOMAC® VA3.1 stiffness subscale (subscale B)
- Difference between JTA-004 and active comparator in mean change from baseline in knee physical function at each follow-up visit using the WOMAC® VA3.1 physical function subscale (subscale C)
- Difference between JTA-004 and active comparator in mean change from baseline in PGA at each follow-up visit
- Difference between JTA-004 and active comparator in mean change from baseline in IGA at each follow-up visit
- Difference between JTA-004 and active comparator in mean change from baseline in subject global health and well-being score at each follow-up visit using the EQ-5D-5L questionnaire
- Difference between JTA-004 and active comparator in responder rate (defined as ≥ 30% pain intensity reduction) at Month 3
- Difference between JTA-004 and active comparator in the mean daily consumption of rescue medications over 6 months
Safety endpoints:
- Adverse Events (AEs) including Serious Adverse Events (SAEs)
- Blood pressure changes after treatment injection (during the 2-hour monitoring period) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/3/6/12 months after treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Hong Kong |
Moldova, Republic of |
Belgium |
Denmark |
Poland |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |