E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic osteoarthritic knee-joint pain |
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E.1.1.1 | Medical condition in easily understood language |
Pain due to degenerative lesions of the knee joint |
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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 | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 | 10003244 |
E.1.2 | Term | Arthritic pains |
E.1.2 | System Organ Class | 100000004859 |
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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 | 10064238 |
E.1.2 | Term | Gonalgia |
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 |
Part I:
The primary objective is the safety and tolerability of intra-articular injection of MTX-071 in incrementing doses based on the incidence, nature and severity of AES/SAEs potentially causally related with the study medication.
Part II:
The primary objective is the safety and tolerability of a second and a third intra-articular injection of MTX-071 on the incidence, nature and severity of AES/SAEs potentially causally related with the study medication.
Documentation of safety data will last for at least 90 (±10) days up to a maximum of 180 (±10) days after injection of MTX-071.
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E.2.2 | Secondary objectives of the trial |
Part I:
• Pain-relieving effect and its duration
• Assessment of a dose-response relationship
• Response to treatment defined as more than a 20% decrease from baseline in mm on the VAS for pain on motion without increase in pain medication, as average of either the last two days or the last seven days
• Influence of treatment on functionality of the knee joint and patients' general feeling of health and estimation of daily life conditions (WOMAC, SF-12 Health Status Survey)
• Use of pain medication
• Acceptance of/satisfaction with treatment as stated by the patients and treating physicians
Part II:
• Pain-relieving effect and its duration
• Response to treatment defined as more than a 20% decrease from baseline in mm on the VAS for pain on motion without increase in pain medication, as average of either the last two days or the last seven days.
• Use of pain medication
• Acceptance of/satisfaction with treatment as stated by the patients and treating physicians.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part I:
- Written informed consent
- Otherwise healthy men or women with knee osteoarthritis aged between 45 and 75 years (extremes included). .
- At least 40 mm on motion and at least 10 mm at rest on the 100 mm-VAS (Visual Analog Scale) for average arthritic joint pain in the knee to be studied during the last 2 days, with or without pain medication.
- Previously documented imaging (e.g. radiography or MRI) showing a Kellgren Lawrence Grade 2 – 4 severity.
- Female patients of childbearing potential or female partners of childbearing potential of male patients must agree to use a reliable contraceptive method for at least one month after the injection of MTX-071.
- Subject is highly likely to comply with the protocol and complete the study.
Part II
- Written informed consent (only before the second injection).
- Patient has received at least one dose of MTX-071 within 3 to 12 months prior to the planned second administration.
- Patient has received at least a second dose of MTX-071 within 3 to 12 months prior to the planned third administration.
- Patient did not experience any treatment related SAE.
- At least 40 mm on motion on the 100 mm-VAS (Visual Analog Scale) for average arthritic joint pain in the knee to be studied during the last 2 days.
- Female patients of childbearing potential or female partners of childbearing potential of male patients must agree to use a reliable contraceptive method for at least one month after the injection of MTX-071.
- Subject is highly likely to comply with the protocol and complete the study.
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E.4 | Principal exclusion criteria |
Part I:
- Knee surgery within 6 months before study start or planned for any time during the next 6 months.
- Any injection into the knee to be studied within the preceding 7 days or trauma to the knee not yet healed.
- History of any cardiovascular, renal, and/or other relevant disease or malignancy.
- History of severe allergic or anaphylactic reactions.
- Pregnancy.
- Major bleeding disorder.
- Clinically significant deviation from the normal laboratory values.
- Clinically significant abnormal ECG
- History of clinically relevant drug/chemical/ substance/alcohol abuse within the past 2 years prior to screening.
- Symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within the past 2 weeks prior to study medication administration.
- Patients positive for human immunodeficiency virus (HIV) antibody, hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg).
- Patients who had a corticosteroid injection in the knee to be studied within 3 months prior to baseline or are planned to get a corticosteroid injection within 4 weeks following the injection of MTX-071.
- Vaccination within 60 days prior to study medication administration.
- Systemic immunosuppressant agent within 6 months prior to study medication administration
- Experimental agent within 30 days or ten half-lives, whichever is longer, prior to study medication administration.
- Any other condition, which in the opinion of the investigator, precludes the subject’s participation in the trial.
- Patients who are dependent on the sponsor or investigator.
Part II:
- Knee surgery since the first administration until last study visit.
- Any injection into the knee to be studied within the preceding 30 days or trauma to the knee not yet healed.
- Pregnancy.
- Clinically significant abnormal ECG.
- Symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within the past 2 weeks prior to study medication administration.
- Patients who had a corticosteroid injection in the knee to be studied between first dose of MTX-071 and the next planned dose of MTX-071.
- Vaccination within 14 days prior to study medication administration.
- Systemic immunosuppressant within the last 6 months prior to the planned administration
- Other experimental agent between MTX-071 study medication administrations.
- Any other condition, which in the opinion of the investigator, precludes the subject’s participation in the trial.
- Patients who are dependent on the sponsor or investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurence of adverse events. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuous assessment up to 6 months after injection. |
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E.5.2 | Secondary end point(s) |
Safety and efficacy endpoints. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part I: 7 days, 30 days, 90 days and 180 days after injection.
Part II: 7 days, 30 days, 90 days and 180 days after injection and 60, 120 and 150 days after injection (telephone call with patient) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 2 |
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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |