| 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 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Symptomatic osteoarthritis of the knee with Kellgren-Lawrence grade II and III |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10023476 |
| E.1.2 | Term | Knee osteoarthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 |
The objective of this study is to assess the safety and efficacy of JTA-004® single intra-articular administration in patients suffering from symptomatic osteoarthritis of the knee at the end of the study period (at Month 6).
Safety:
At each follow-up visit, patients will be assessed for the occurrence of any (serious) adverse events using patient open non-directive questionnaire, physical examination (including vital signs), and laboratory measurements. The safety analyses will be based on incidence evaluation of treatment emergent adverse events by preferred term and body system. Laboratory measurements will be compared to the normal laboratory ranges and to laboratory measurements obtained at Baseline Visit.
Efficacy:
Primary study objectives are (i) the selection of the best JTA-004® strength and (ii) the superiority assessment of the best JTA-004® strength efficacy to the reference or (iii) stop the trial at interim analysis for futility. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary efficacy endpoints are:
-WOMAC® VA3.1 pain subscale (WOMAC® subscale A) at Month 3
-WOMAC® VA3.1 total score over the time
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
-Male/female aged between 50 to 79 years.
-Ambulatory (able to walk unassisted, the use of a crutch or a walking stick is allowed)
-Diagnosed with primary knee OA, fulfilling the following American College of Rheumatology (ACR) criteria at the target knee:
•Pain ≥ 40 mm on a 0-100 mm VAS during the 3 days preceding the date of the Screening Visit (see Annex 2)
•Morning stiffness not exceeding 30 minutes
•Kellgren-Lawrence grade II or III (confirmed by X-ray within the last 6 months)
-Insufficient/failed response to analgesics and/or NSAID
-Willing and able to abstain from physical therapy of the knee, and knee braces for the entire duration of study
-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 "anonymized" data
|
|
| E.4 | Principal exclusion criteria |
-Isolated symptomatic femoropatellar osteoarthritis of the target knee
-History of trauma or surgery or arthroscopy at the target knee within 6 months before inclusion
-Concomitant inflammatory disease or other condition affecting the joints (e.g., rheumatoid arthritis, septic arthritis, inflammatory joint disease, metabolic bone disease, psoriasis, gout, microcrystalline arthropathies/chondrocalcinosis, Paget’s disease)
-Any musculoskeletal condition (such as hip osteoarthritis, amputation, neurologic disorder) that would impede measurement of efficacy at target knee
-Target knee prosthesis planned within 12 months after the Screening Visit
Current or previous diagnoses, signs and/or symptoms
-Uncontrolled diabetes mellitus, end-stage hepatic or renal disease documented in the patient’s file
-Current (or within the last 5 years prior to entering the study) history of solid or haematological neoplasia or bone marrow transplantation (except for basal cell carcinoma and completely excised squamous cell carcinoma)
-Other severe acute or chronic medical or psychiatric conditions or pre-dispositions or laboratory abnormalities, as judged by the Investigator
-Current or past history of coagulation disorders, as judged by the Investigator
-Hypersensitivity to any components of HA-based injection products
-History of hypersensitivity to human biological material including blood and blood derived products, potential excipients and residues from manufacturing process, documented clinically or by laboratory tests
-Hypersensitivity to avian proteins
-Life expectancy less than 6 months
Current or previous treatment
-Participation in another clinical study within 6 months prior to Screening
-Patients previously treated with JTA-004®
-Treatment:
•Within 6 months prior to Screening: intra-articular hyaluronic acid injection at the target knee
•Within 2 months prior to Screening: intra-articular glucocorticoids at the target knee
-Current chemo-, radio- or immuno-cancer-therapy or immunosuppressive therapy
-Current anti-hypertensive medication the effects of which are known to be potentiated by a single dose of clonidine
-Current (or within 6 months prior to Screening) illicit drug abuse
Safety aspects concerning female subjects of childbearing potential
-Females who are pregnant, lactating or woman with childbearing potential (last menstrual bleeding less than 12 months ago) unwilling to use medically acceptable contraception, or women with childbearing potential unwilling to perform a pregnancy test before administration of study treatment.
Other exclusion criteria
-Body Mass Index (BMI) of 35 kg/m2 or greater
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The WOMAC® VA 3.1 pain subscale scoring at baseline and subsequent assessment time points is the major efficacy criteria |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and efficacy endpoints will be evaluated at each of the 3 follow-up visits during the 6-month follow-up period (notably at 2 weeks, 3 months and 6 months after study drug administration).
For selection of best JTA-004® strength, by comparing the different JTA-004® strengths to the reference with respect to the WOMAC® VA3.1 pain subscale score (mean differences between baseline and Month 3)
For superiority assessment, by comparing the best JTA-004 strength and reference on the mean differences in WOMAC® VA3.1 pain subscale score between baseline and Month 6, assuming a mean between group difference of 7 mm with a standard deviation of 10 mm. |
|
| E.5.2 | Secondary end point(s) |
-WOMAC® VA3.1 pain subscale (WOMAC® subscale A) at Month 3
-WOMAC® VA3.1 total score over the time
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-WOMAC® VA3.1 pain subscale (WOMAC® subscale A) at Month 3
-WOMAC® VA3.1 total score over the time |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| This study is a seamless two-stage prospective,randomized,double-blind controlled Phase II/Phase III |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 15 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 30 |
Print
