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 |
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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 | 21.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective of this study is to evaluate the efficacy and safety of a single intra-articular (IA) injection of PTP-001 in patients with osteoarthritis (OA) of the knee for up to 26 weeks and to determine the most suitable dose of PTP-001 for Phase 3.
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E.2.2 | Secondary objectives of the trial |
• To evaluate the change from pretreatment baseline in pain intensity assessed by participant self-report (WOMAC Pain subscale) during the trial • To evaluate the change from pretreatment baseline in function assessed by participant self-report (WOMAC Function subscale) • To evaluate change from pretreatment baseline in the weekly average of daily pain assessed by patient self-report (NRS) • To evaluate the change from pretreatment baseline in patient global assessment of OA (PGA-OA) assessed by participant self-report • To evaluate the change from pretreatment baseline in health-related quality of life (HRQL) self-report on the 36 Item Short Form Survey (SF-36), overall score, physical component score (PCS), and mental component score (MCS) • To evaluate the response to PTP-001 on the OMERACT-OARSI responder criteria |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Immunology Panel Sub-study will be performed in a sub-group of patients to evaluate the presence of antibodies against HLA-G as well as to assess the preexistence antibodies against human cell surface antigens. |
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E.3 | Principal inclusion criteria |
1. Male or female, aged 40 to 80 years 2. Symptomatic knee OA with Kellgren-Lawrence (KL) radiographic classification of 2, 3, or 4 (mild, moderate, or severe) as assessed by the central reading facility 3. IF KL radiographic classification of 4 (KL 4) is assessed by the central reading facility, participant must not have prior a referral from their treating physician for arthroplasty of the target knee 4. Target knee pain ≥ 20 and ≤ 40 out of 50 the WOMAC®NRS 3.1 pain questionnaire (sum of 5 questions) at screening and baseline 5. Onset of symptomatic OA of the target knee was at least 6 months prior to screening 6. Insufficient or failed response or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs, as reported by the participant 7. IF FEMALE, must meet all of the following: • Not breast feeding • Not planning to become pregnant during the study • If of childbearing potential, must have a negative pregnancy test result within 72 hours prior to receiving the intra-articular injection, and must commit to the use of a highly effective form of birth control (See Appendix A) for at least 12 weeks after the injection 8. Willingness to remain on the same oral “rescue” (as needed) analgesic as the only pharmacologic treatment for knee pain during the study 9. Willingness to abstain from taking any illicit or unauthorized medications for treatment of OA or any other concurrent condition during the study 10. Written informed consent is obtained from the participant
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E.4 | Principal exclusion criteria |
- Participant is non-ambulatory (unable to walk >50 feet without assistance) - Clinically severe obesity as defined by the National Institutes of Health (body mass target ≥40 kg/m2) at screening or baseline - Contralateral knee pain equal to or exceeding the pain in the target knee (on the WOMAC® NRS3.1 pain questionnaire) at screening and/or baseline - Clinically significant effusion of the target knee at either the screening or baseline visits determined by physical examination (e.g., ballotable patella or positive bulge sign). Note: Participants presenting with effusion may be enrolled in the study after undergoing knee aspiration to remove excess fluid in the target joint. - Severe (excessive) malalignment of the tibial-femoral axis, assessed radiographically - Presence of active infection of the target knee or systemic infection requiring treatment within the 3 months prior to screening - Clinical diagnosis of inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, etc.) established by clinical history, examination, or serology - Chronic use of narcotics or alcohol abuse within the past 6 months prior to screening - Surgery to the target knee (including arthroscopy) within 6 months prior to receiving the intra-articular injection or planned surgery to the target knee within 6 months after the injection - Participant previously underwent arthroplasty of the target knee 13. Symptomatic OA of the non-target knee that is not responsive to paracetamol (acetaminophen) or oral nonsteroidal anti-inflammatory drugs (NSAIDs). 15. Osteonecrosis of either knee 16. Significant acute (within the past 3 months) injury to the target knee |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Change from pretreatment baseline in the WOMAC pain sub-score (questions 1 to 5) in the target knee of the 2 PTP-001 doses and the saline control vehicle at 6 months. Safety: Physical examination, laboratory values, AEs, AESI, and immunogenicity testing |
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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) |
• Change from pretreatment baseline in participant self-reported pain at the target knee as assessed by WOMAC Pain subscale score • Change from pretreatment baseline in participant self-reported functional capacity of the target knee measured by WOMAC Physical Function subscale score • Change from pretreatment baseline in weekly average of daily pain score (NRS) • Change from pretreatment baseline in patient global assessment of OA by PGA-OA • Change from pretreatment baseline in participant self-reported quality of life measured by SF-36 overall score, PCS, and MCS • Proportion of participants meeting OMERACT-OARSI responder criteria
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 2 weeks, 3 months, 4 months, 5 months, and 6 months
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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 | 3 |
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 | 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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |