E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Injury of the knee Cartilage. Mains symptoms of cartilage lesions are pain, joint swelling, and loss of function. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007710 |
E.1.2 | Term | Cartilage injury |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 |
The primary objective is to evaluate the efficacy of three weekly i.a. injections of 10, 30, or 100 µg AS902330 in patients with acute cartilage injury of the knee based on MRI measurements of the defect volume. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to support the efficacy of AS902330 in patients with acute cartilage injury of the knee by morphological and symptomatic outcome scores as well as to confirm its safety and local tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion, all of the following criteria must be fulfilled:
· Acute cartilage lesion of ICRS grade 2 to 4 at the femoral condyle of the knee (= target knee)
· Age: 18 to 45 years
· Sex: male or female. Women of childbearing potential (i.e. all female patients after
puberty unless they are post-menopausal for at least two years or surgically sterile)
must have negative serum and urine pregnancy tests at screening and Visit 1, respectively, and must use a highly effective method of contraception (i.e. two barrier methods or hormonal intrauterine device or use of an oral female contraceptive) from 4 weeks prior to the first dose until 12 weeks after the last dose of trial medication
· History of pain and effusion of the target knee post-injury
· Injury within 4 to 12 weeks prior to 1st treatment with IMP
· Written informed consent prior to any trial-related activity |
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E.4 | Principal exclusion criteria |
• Personal medical history of OA in either knee
• Any previous surgery on the target knee
• History of swelling of the target knee along with pain on weight-bearing, or arthroscopy for diagnostic purposes during the 12 months preceding injury
• Corticosteroid (i.a.) injection into the target knee during the preceding 12 months
• Any other i.a. injection into the target knee during the preceding 3 months
• Any concurrent injury (e.g. arthrolith, anterior cruciate ligament rupture, meniscus tear) of the target knee requiring surgical intervention
• OA or any pre-existing cartilage damage in the target knee, as revealed by MRI
• Open growth plate, as revealed by MRI
•Diagnostic arthroscopy after injury and within 4 weeks prior to treatment start
• Legal incapacity or limited legal capacity
• Patients who are imprisoned or institutionalized by regulatory or court order
• Pregnancy or lactation
• Participation in another clinical trial within the past 30 days
• Any condition or findings in the medical history or in the pre-trial assessments that in the opinion of the Investigator constitutes a risk or contraindication for participation in the trial or that could interfere with the trial objectives, conduct or evaluation
• Known hypersensitivity to the trial treatment or diluents
• Significant renal or hepatic impairment, as indicated by
o Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (AP) >3 times the upper limit of normal (ULN)
o Total bilirubin >1.5 times ULN (except in case of Gilbert’s syndrome)
o Creatinine >1.5 times ULN
• Hemoglobin <5.5 mmol/L, white blood cell count (WBC) <2.5 x 109/L, or platelets <75 x 109/L).
• Any suspicion of i.a. infection
• Any known active infections that may compromise the immune system such as HIV,
Hepatitis B or C infection
• History of sarcoma and/or of other active malignancy within five years, except
adequately treated basal cell or squamous cell carcinoma of the skin |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in cartilage defect volume over 12 months based on central magnetic resonance imaging (MRI). |
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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) |
Efficacy (in order of priority):
(a) The relative and absolute changes in cartilage defect volume and thickness in the target knee from baseline to 6 months and the absolute changes over 12 months
(b) Changes in the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for the integration of rebuilt cartilage and its surface structure at 3, 6 and 12 months
(c) Changes in the Boston Leeds Osteoarthritis Knee Score (BLOKS) at 12 months
(d) Changes in the ICRS grades over 6 and 12 months
(e) The relative and absolute change in cartilage defect volume/thickness in the target knee from baseline to 3 months
(f) Changes in the symptom scores (Knee Injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee [IKDC], global evaluation of treatment benefit) at visits over 12 months
Safety:
• Systemic and local AEs over 12 months
• Acute inflammatory events, i.e., increase of pain of at least 30 mm on a 100 mm visual analog scale (VAS) along with selfreported swelling within 3 days post-injection
• Changes in safety laboratory measurements and vital signs over 12 months
• Occurrence of FGF18ab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Serbia |
South Africa |
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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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For administrative and safety reporting purposes the end of the study will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all study sites. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |