A phase 2b Study Evaluating the Efficacy of a Single Injection Autologous Adipose Derived Mesenchymal Stromal Cells inPatients with Knee Osteoarthritis

Phase 1

Conditions: Active knee Osteoarthritis (mild to moderate)
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2015-002125-19-IE

Lead Sponsor: CHU Montpellier

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 153

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 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1)Previous treatments acting on cartilage or bone metabolism (eg, oral or intravenous bisphosphonates <1 year previously, denosumab < 6 months, strontium ranelate or teriparatide or raloxifene <7 days prior to selection, and oral glucosamine =1500 mg/day or chondroitin sulphate =1000 mg/day <3 months previously)
2)Has had any trauma of the index knee in the previous 12 months prior to the screening visit
3)Has OA of the index knee that meets K-L classification criteria of grade 1 or 4
4)Osteoarthritis causing significant pain in any joint other than the identified knee, i.e., pain in hip, or contralateral knee (= 20 mm pain) as confirmed by a separate VAS at baseline for any other painful joint concerned
5)Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 12 months of screening (Not applicable in Germany and Netherland)
6)Prior to the screening visit, has received:-Oral corticosteroid therapy within the previous 3 month, OR-Intramuscular, intravenous or epidural corticosteroid therapy within the previous 6 months, OR-Intra-articular injection of corticosteroids in the index within the previous 6 months, OR
-Intra-articular injection of hyaluronic acid in the index knee within the 6 months. OR-Intra-articular injection of platelet rich plasma in the index knee within the 6 months.
7)Inflammatory or other rheumatic diseases defined by clinical examination and previous serum markers (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)), History or evidence of infectious arthritis, Paget’s disease, Ochronosis, Wilson’s Disease, Primary osteochondromatosis
8)History of articular fracture of the target knee joint
9)History of heritable disorders (e.g. hypermobility) and collagen gene mutations
10)Immunodeficiency diseases
11)Alcoholics not in treatment and still drinking (14+ drinks/week)
12)Subjects with poorly controlled diabetes mellitus (HbA1C > 8%) or known concomitant vascular problems
13)Planned longer stay outside the region that prevents compliance with the scheduled visit
14)Severe misalignment of the knee (excessive varus or valgus = 8°) at physical examination, as confirmed by standard radiograph
15)Severe osteoporosis with previous symptomatic vertebral or hip fractures
16)History of joint replacement of the knee or hip within the previous 12 months
17)Serious systemic diseases or infectious/inflammatory skin diseases in the area of the affected knee
18)Positive serology for HIV, hepatitis B, C and syphilis
19)History of cancer or blood dyscrasias, or previous chemotherapy, radiotherapy or immunotherapy
20)Contraindication to MRI, including MRI-incompatible internal devices (pacemaker, neurostimulator, cochlear implant, ocular foreign bodies, foreign bodies close to neurovascular structures)
21)Intolerance or allergy to local anaesthesia
22)Anticoagulant treatment
23)Overweight with body mass index greater than 35 (obesity grade II).
25)Abnormal blood tests:
-Hepatic (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] > 2 × upper limit of normal [ULN]),-Renal (clearance < 30 ml/min/1,73 m2),pancreatic or biliary disease, except asymtomatic bile stones-Blood coagulation disorders, Anaemia (= 10 g/dL) or platelet count of = 100 × 109/L
26)Significant

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of a single intra-articular injection of ASC in mild to moderate knee OA (KL 2-3) based on increase in the number of strict” responders defined by improvements from baseline in WOMAC pain or physical function subscores 50% with absolute changes 20 mm at 6 month, compared to placebo (vehic: 0.5% glucose in saline with 4.5% alb);Secondary Objective: -Kellgren-Lawrence scores assessment on the basis of X-rays <br>-Progression of affected knee joints by quantitative MRI<br>-Disability and life quality assessment<br>-OARSI response assessment <br>-Paracetamol (Acetaminophen) medication assessment<br>- Use of painkillers assessment;Primary end point(s): the primary endpoint is to evaluate the efficacy of ASC in mild to moderate knee OA based on increase in the rate of strict” responders at 6 month, compared to placebo (vehicle: 0.5% glucose in saline with 4,5% human albumin;Timepoint(s) of evaluation of this end point: Month 6

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Potential structural benefit determined by the following <br>Kellgren-Lawrence scores will be assessed on the basis of X-rays at timepoint 0, month 12 and 24<br>-Progression of affected knee joints by quantitative MRI at timepoint 0, month 12 and 24<br>Disability and life quality assessment at timepoint 0, month 1,3,6,12 and 24<br> Osteoarthritic Research Society Iternational (OARSI) response at month 1,3,6, 12 and 24<br>Paracetamol (Acetaminophen) medication consumption at each visit<br>-SAS score<br>-VAS pain in the affected knee<br>-SF-36 score<br>-patient and physician global assessments of disease activity (VAS)<br>-Adverse events will be evaluated at each visit.<br>;Timepoint(s) of evaluation of this end point: Timepoint baseline, visit 2, day 0, day 7 and Months 1, 3, 6, 12 and 24

Related Trials