| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pain due to osteoarthritis of the knee or hip |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pain of the knee or hip due to a joint disease that results from breakdown of joint cartilage and underlying bone |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
| 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 |
|
| 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 | 10020108 |
| E.1.2 | Term | Hips osteoarthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 of the study is to evaluate the efficacy of fasinumab compared to placebo, when administered for up to 24 weeks in patients with osteoarthritis (OA) of the knee or hip. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To evaluate the efficacy of fasinumab compared to non-steroidal anti-inflammatory drugs (NSAID)s, when administered for up to 24 weeks in patients with OA of the knee or hip
• To assess the safety and tolerability of fasinumab compared to placebo and compared to NSAIDs, when administered for up to 24 weeks in patients with OA of the knee or hip |
|
| 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 |
| Optional Pharmacogenomic sub-study |
|
| E.3 | Principal inclusion criteria |
Key Inclusion Criteria (additional criteria may apply at screening):
1. A clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit.
2. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (paracetamol/acetaminophen to be taken as needed with a maximum daily dose of 2500 mg in Europe and 2600 mg in countries outside of Europe)
3. A history of at least 12 weeks of inadequate pain relief or intolerance to analgesics used for pain due to OA of the knee or hip
4. Currently using a stable dose of NSAID
5. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment |
|
| E.4 | Principal exclusion criteria |
Key Exclusion Criteria (additional criteria may apply at screening):
1. Non-compliance with the numeric rating scale (NRS) recording during the pre-randomization period
2. History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy
3. History or presence on imaging of arthropathy, hip or knee dislocation, extensive subchondral cysts, evidence of severe structural damage, bone collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures
4. Trauma to the index joint within 3 months prior to the screening visit
5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening
6. Patient is not a candidate for magnetic resonance imaging (MRI)
7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed
8. History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
9. Evidence of autonomic neuropathy as defined in the schedule of assessments (SoAs)
10. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
11. Use of systemic corticosteroid within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit
12. Exposure to an anti-NGF antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies
13. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 20 weeks after the last dose |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The co-primary endpoints are:
1. Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores from baseline to week 24 in patients treated with fasinumab compared to patients treated with placebo.
2. Change in the WOMAC physical function subscale scores from baseline to week 24 in patients treated with fasinumab compared to patients treated with placebo.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Change from baseline to week 24 in Patient Global Assessment (PGA) in patients treated with fasinumab compared to patients treated with placebo
2. Percentage of patients treated with fasinumab, compared to patients treated with placebo, who had a response at week 24, with response defined as an improvement by ≥30% in WOMAC pain sub scale score
3. Change from baseline to week 24 in WOMAC pain subscale scores in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms)
4. Change from baseline to week 24 in WOMAC physical function subscale scores in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms)
5. Change from baseline to week 24 in PGA score in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms)
The safety endpoints in this study are:
1. Incidence of AA (as confirmed by independent adjudication)
2. Incidence of DA (as confirmed by independent adjudication)
3. Incidence of TEAEs
4. Incidence of sympathetic nervous system dysfunction (as diagnosed after consultation with a neurologist and/or cardiologist)
5. Incidence of peripheral sensory AEs that require a neurology consultation
6. Incidence of all-cause joint replacements (JRs) through week 24 and through the follow-up period (week 44)
7. Incidence of JR at telephone survey 52 weeks after completion of study
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints:
- Baseline to Week 24
Safety endpoints:
- endpoints 1-5 - Baseline through Week 44;
- endpoint 6 - Bsaeline through Week 24 and Week 44;
- endpoint 7 - Week 72 |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 46 |
| 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 |
| Australia |
| Canada |
| Denmark |
| Estonia |
| Germany |
| New Zealand |
| Poland |
| Romania |
| South Africa |
| United Kingdom |
| United States |
|
| 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
|
| The end of the study for this study is defined as the last phone contact for the last patient. |
|
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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