E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
osteochondral defects of the knee (early osteoarthritis) |
|
E.1.1.1 | Medical condition in easily understood language |
early osteoarthritis of the knee |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
|
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 principal research question is to find out if treatment with either a patient's own cartilage cells (chondrocytes), or bone marrow-derived stromal cells (containing stem cells), or a combination of the two cell types, give a different clinical outcome, in terms of knee function, for patients with early osteoarthritis of the knee. |
|
E.2.2 | Secondary objectives of the trial |
Do different cell types (cartilage cells, bone marrow-derived stem cells, or a combination) give a different quality of structural cartilage repair as judged by histology, MRI images and arthroscopic score?
Do different cell types delay or prevent joint replacement to a different degree?
How do cell therapies help cartilage and bone regeneration?
Can we optimise cell therapy according to patient selection, cell culture characteristics, manner of implantation and method of rehabilitation?
How do the treatment costs compare between the three treatments? |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A symptomatic chondral defect of the knee that extends to (Outerbridge grade 4) or into the subchondral bone. 2. The defect is considered suitable for treating with autologous cell therapy. 3. Previous surgical treatment of the defect has failed to relieve symptoms.
|
|
E.4 | Principal exclusion criteria |
1. Positive for HIV, hepatitis B or C, syphilis, or human T cell lymphotrophic virus (HTLV) I or II. 2. Likely to show contraindications to autologous cell therapy: patients with inflammatory condition, history of mesenchymal tumours, therapy with steroids or methotrexate, bleeding tendency or known anaphylaxis to any product used in cell preparation. 3. Low probability of compliance with physiotherapy or follow−up, including a major life−threatening condition.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The Lysholm Score: A measure of clinical and functional outcome that has been optimised for patients who have undergone cell therapy for joint damage of the knee. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
15 months after cell implantation |
|
E.5.2 | Secondary end point(s) |
1. Incidence of adverse events 2. Quality of repair tissue using MRI and histology of cartilage biopsy (currently unfunded,the ability to investigate this outcome is contingent on obtaining sufficient funding) 3. Health related quality of life and other patient-reported outcome measures 4. Number of years free from further surgery 5. Observed patterns of rehabilitation and compliance to physiotherapy schedules 6. Unit costs per treatment |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Adverse events and Serious adverse events will be recorded until 15 months post cell implantation. This constitutes the defined 'end of trial'. However, a non-interventional follow-up phase will continue until Year 20 whereby critical SAE's, as defined in the study protocol, will be captured using databases such as national cancer and joint replacement registries. 2 & 3. 15 months post cell implantation. 4. Up to 20 years post cell implantation 5 & 6. 15 months post cell implantation.
|
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
other investigational medicinal product - autologous chondrocytes |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
LVLS; (a non interventional follow-up phase, will continue until year 20 post cell implantation) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 29 |