E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritis of the Knee |
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E.1.1.1 | Medical condition in easily understood language |
Osteoarthritis of the Knee |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031165 |
E.1.2 | Term | Osteoarthritis knee |
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 evaluate the efficacy and safety of a single injection of Cingal for relief of joint pain in subjects with Osteoarthritis (OA) of the knee who have not responded to conservative treatment. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Screening : 1. 40-75 years old, Body Mass Index (BMI) ≤ 40 kg/m2. 2. Kellgren-Lawrence (K-L) severity grade I, II or III in the index knee as determined by X-ray. Contralateral knee: K-L severity grade 0, I or II. 3. at least two signs and at least two symptoms of OA disease (based on the EULAR recommendations) in the index knee for at least 6 months despite conservative treatment (weight reduction, physical therapy, pain medications, etc.). The EULAR signs and symptoms are as follows: o Signs: crepitus, restricted movement and bony enlargement o Symptoms: persistent knee pain, limited morning stiffness and reduced function 4. willing to abstain from other IA treatments of the knee for the duration of the study. 5. willing to discontinue all analgesics including NSAIDs, except acetaminophen/paracetamol, at least seven days before the treatment injection and through the completion of the study. 6. willing to use only acetaminophen/paracetamol for the treatment of joint pain for the duration of the study. At least forty eight hours prior to the Baseline Visit and each follow-up visit, willing to discontinue use of acetaminophen/paracetamol. 7. willing to maintain a stable dose of oral glucosamine and/or chondroitin sulfate products throughout the study 8. able to understand and comply with the requirements of the study and voluntarily provides consent.
Baseline: 1. WOMAC pain-sub-score ≥ 40 mm and ≤ 90 mm in the affected knee and ≤ 30 mm in the contralateral knee on a 100 mm Visual Analog Scale (VAS) scale. |
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E.4 | Principal exclusion criteria |
Screening: 1. received an IA injection of Hyaluronic Acid (HA) and/or steroid in either knee within 6 months of signing the informed consent form (ICF). A subject will be excluded if they are planning to receive an HA or steroid injection (other than the study injection) in either knee during the course of this study. 2. had an arthroscopy of either knee within 3 months of signing the ICF. 3. had an open surgical procedure of either knee or hip or any surgery of the spine within 12 months of signing ICF. Subject plans to have knee, hip or spine surgery within the study period. 4. has intra-articular trauma to the index knee. Subject has concurrent multi-system or multi-limb trauma. 5. has evidence or medical history of the following diseases in the index knee: septic arthritis; inflammatory joint disease; history of Reiter’s syndrome; gout; chondrocalcinosis associated with recurrent episodes of acute synovitis of the knee consistent with pseudogout; osteochondritis dissecans, Paget disease of the bone; ochronosis; acromegaly; hemochromatosis; primary osteochondromatosis; known history of Wilson disease; heritable disorders or collagen gene mutations. 6. has a history of cartilage repair surgery in the index knee within 3 years of signing the ICF. 7. has a history of ACL repair, reconstruction or injury in the index knee within 3 years of signing the ICF. 8. has X-ray findings of acute fractures, severe bone loss, avascular necrosis, severe bone or joint deformity in the index knee. 9. has significant varus or valgus deformity greater than 10 degrees in either knee. 10. has a clinically apparent tense effusion of the index knee. 11. has knee instability in either knee per the Investigator’s assessment. 12. requires consistent use of an assistive device (e.g. wheelchair, walker, etc.) Occasional use of a cane is acceptable. 13. has medical condition(s) which could affect study assessments or may adversely affect the safety and/or success of the study treatment. (for list of potential conditions refer to protocol) 14. is taking medications at the time the subjects signs the ICF which could interfere with the treatment procedure, healing and/or assessments. This includes but is not limited to oral or injectable anticoagulant treatments, anti-aggregant platelet treatment, chronic opioid analgesics. Low dose aspirin used for cardiovascular protection is allowed if a stable regimen is maintained for the duration of the study. 15. is receiving treatment using electromagnetic stimulation and/or low intensity ultrasound in the index knee at the time of signing the ICF, within 3 months of signing the ICF or plans to receive treatment any time during the study period. 16. had an oral, intramuscular, intravenous, rectal suppository or topical (excluded in index knee only) corticosteroid within 30 days of signing the ICF are excluded. Topical corticosteroid use at any site other than the index knee is allowed. 17. has a pre-treatment contraindication to IA injections or aspiration of the index knee, including cutaneous infection in the injection site area, active IA infection (as suggested by moderate or marked effusion), knee deformity or condition which, in the opinion of the Investigator could jeopardize the sterility or delivery of the IA injection. 18. with a history of hypersensitivity to any of the ingredients in the hyaluronan or previous hypersensitivity to the administration of corticosteroids or an inability to tolerate acetaminophen/paracetamol. 19. has any contraindication to the receipt of a corticosteroid. 20. is receiving or in litigation for worker’s compensation. 21. is a woman who is pregnant or breastfeeding at the Screening Visit or a woman of child bearing potential who refuses to use effective contraception during the course of the study. 22. was involved in any other research study involving an investigational product, or a new application of an approved product, within 60 days of signing the ICF.
Baseline: 1. has a decrease of ≥ 20 mm in the WOMAC pain-sub-score (average of 5 pain scales) from Screening to Baseline in the index knee on a 100 mm Visual Analog Scale (VAS) scale. 2. has a synovial fluid aspirate volume > 20 mL in the index knee. 3. has a contraindication to continue with the study treatment injection based on the visual appearance of the synovial fluid aspirate unless the fluid is examined microscopically prior to injection with no clinically significant findings (e.g. bacteria, crystals or blood). 4. has range of motion of less than 100° flexion in either knee. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The change from baseline in knee pain as measured by the WOMAC Pain Score (100 mm VAS) at 26 weeks post treatment comparing the Cingal group to the TH group.
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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) |
* The change from baseline in knee pain as measured by the WOMAC Pain Score (100 mm VAS) at 3 weeks post treatment comparing the Cingal group to the Monovisc group. * The responder rate as identified by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responder index at 26 weeks post treatment comparing the Cingal group to the TH group. * The change from baseline in WOMAC Physical Function score at 26weeks post treatment comparing the Cingal group to the TH group. * The change from baseline in WOMAC Stiffness score at 26 weeks posttreatment comparing the Cingal group to the TH group. * The change from baseline in Total WOMAC score at 26 weeks post treatment comparing the Cingal group to the TH group. * The change from baseline in the Patient Global Assessment at 26 weeks post treatment in the Cingal group compared to the TH group. * The change from baseline in the Evaluator Global Assessment at 26 weeks post treatment in the Cingal group compared to the TH group. * The change from baseline in knee pain as measured by the WOMAC Pain Score (100 mm VAS) at 1 week post treatment comparing the Cingal group and the Monovisc group. *The usage of rescue medication through 26 weeks post treatment in the Cingal group compared to the TH group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3 and 26 weeks post 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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |