E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active knee Osteoarthritis (mild to moderate) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
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 |
Evaluate the efficacy of a single intra-articular injection of ASC in mild to moderate knee OA (KL 2-3) based on improvement of WOMAC pain and function subscore at 6 month, compared to placebo (vehic: 0.5% glucose in saline with 4% alb) |
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E.2.2 | Secondary objectives of the trial |
- Kellgren-Lawrence scores assessment on the basis of X-rays
- Progression of affected knee joints by quantitative MRI
- Disability and life quality assessment
- OARSI response assessment
- Paracetamol (Acetaminophen) medication assessment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Symptomatic mild to moderate osteoarthritis (OA) of the index knee as defined by the American college of Rheumatology (ACR):
- History of pain in the index knee ≥ 6 months, AND
- Kellgren-Lawrence (K-L) Grade 2 or 3 only, on plain radiographs of the index knee (including fixed flexion), AND
- Swelling of the index knee evaluated by the investigator
2. Must meet the following pain criteria at the time of screening/baseline visit since at least half of the days in the previous month:
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscores ≥ 40 mm on the 0-100 normalised scale
- Visual Analogic Scale (VAS) pain rating of at least 40 on a 100-mm scale
- Subject’s global assessment of arthritis status must be fair, poor, or very poor
-Subject’s global assessment of the contralateral knee <20 mm by 100-mm using Visual Analogic Scale (VAS)
3. NSAID washout of at least 2 days before screening/baseline
4. BMI between 20-35 kg/m2 |
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E.4 | Principal exclusion criteria |
1. Previous treatments acting on cartilage or bone metabolism (eg, oral or intravenous bisphosphonates <1 year previously, strontium ranelate or teriparatide or raloxifene <7 days prior to selection, and oral glucosamine ≥1500 mg/day and chondroitin sulphate <3 months previously)
2. Prior to the screening visit, has received intra-articular injection of corticosteroids, platelet rich plasma or hyaluronic acid within the previous 6 months,
3. Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 12 months of screening.
4. Kellgren-Lawrence Grade 1 or 4 in the index knee.
5. Osteoarthritis causing significant pain in any joint other than the identified knee, i.e., pain in hip, back, or contralateral knee (≥ 20 mm pain) as confirmed by a separate VAS at baseline for any other painful joint concerned
6. History of joint replacement of the knee or hip within the
previous 12 month
7. Diagnosis of one or more of the following:
- Inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder, seronegative spondyloarthritis, gout or pseudogout (defined as acute episodic attacks of swollen, painful joint in a patient with X-Ray chondrocalcinosis or CPPD crystals);
- Severe misalignment of the knee (excessive varus or valgus ≥ 8°) at physical examination, as confirmed by standard radiograph
- Severe osteoporosis with previous fractures |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Analysis:
- Improvement from baseline to month 6 in WOMAC pain score of the index knee.
-Improvement from baseline to month 6 in WOMAC physical function score of the index knee. |
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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) |
- Changes from baseline to months 1, 3, 6, 12 and 24 in OARSI scores of the index knee.
- Changes from baseline to months 1, 3, 6, 12 and 24 in VAS pain scores of the index knee.
- Changes from baseline to months 1, 3, 6, 12 and 24 in WOMAC stiffness scores of the index knee
- Changes from baseline to months 1, 3, 6, 12 and 24 in WOMAC global scores of the index knee
- Changes from baseline to months 1, 3, 12 and 24 in WOMAC pain and function scores of the index knee
- Changes from baseline to months 1, 3, 6, 12 and 24 in KOOS scores of the index knee
- Changes from baseline to months 1, 3, 6, 12 and 24 in SAS scores of the index knee
- Changes from baseline to months 1, 3, 6, 12 and 24 in SF-36
- Changes from baseline to months 12 and 24 in cartilage volume/thickness of the index knee MRI (MOAKS score).
- Changes from baseline to months 12 and 24 in femorotibial joint space of the index knee on X-ray |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Months 1, 3, 6, 12 and 24 |
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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 | Yes |
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 | Yes |
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 | 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 | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |