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 |
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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 |
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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 | 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020108 |
E.1.2 | Term | Hips 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 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 pain due to osteoarthritis (OA) of the knee or hip. |
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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 pain due to 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 pain due to OA of the knee or hip •To characterize the concentrations of fasinumab over time when administered for up to 24 weeks in patients with pain due to OA of the knee or hip •To evaluate the immunogenicity of fasinumab administered for up to 24 weeks in patients with pain due to OA of the knee or hip |
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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 |
Optional Pharmacogenomic sub-study |
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E.3 | Principal inclusion criteria |
Key Inclusion Criteria (additional criteria may apply at screening): 1. Male and female patients, at least 18 years of age, at screening 2. Provide signed informed consent 3. Body mass index ≤39 at screening visit 4. 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, with the following definitions: -The index joint is defined as the joint with OA under evaluation for this study -A joint previously treated with JR surgery cannot be the index joint -A joint previously surgically modified within the past year cannot be the index joint (with the exception of cruciate ligament reconstruction surgery, patellar fracture repair surgery, or meniscal repair) -If a patient has a K-L score of ≥2 at more than 1 knee or hip joint, the index joint is the joint with the greatest WOMAC pain subscore at the screening visit. - If 2 or more knee or hip joints have a K-L score of ≥2 and the same WOMAC pain subscore, the index joint is the joint with the greater K-L score. - If 2 or more joints have a K-L score of ≥2, the same WOMAC pain subscores, and the same K-L scores, then the investigator may choose 1 of these joints as the index joint 5. Moderate to severe pain in the index joint defined as a WOMAC average pain subscale score of ≥4 at both the screening and randomization visits 6. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol to be taken as needed with a maximum daily dose of 2500 mg [countries where 500 mg strength tablets/capsules are available] or 2600 mg [countries where 325 mg strength tablets/capsules are available]) 7. A history of at least 12 weeks of analgesic use for pain due to OA of the knee or hip, as defined by a. Inadequate pain relief from acetaminophen/paracetamol AND b. Intolerance to or inadequate pain relief from opioid or tramadol therapy, unwillingness to take opioid or tramadol therapy for a medically acceptable reason, or lack of access to an opioid or to tramadol 8. Currently using a stable dose of NSAID, defined as using oral NSAIDs at regularly prescribed doses for approximately 4 days per week over the last 4 weeks (patients who are screen failures prior to the randomization visit but who met the NSAID use criterion at screening would still meet this criterion if they are eligible for rescreening) 9. Willing to continue a stable dose of oral NSAID during the screening period, defined as using NSAIDs for approximately 4 days per week 10. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment 11. Stable treatment with glucosamine sulfate and chondroitin sulfate treatments must be stopped during the pre-randomization period 12. Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator 13. Willing to maintain current activity and exercise levels throughout the study 14. Willing and able to comply with clinic visits and study-related procedures and willing to provide follow-up information related to any JR surgery that occurs within the period of time covered by their intended participation in the study 15. Able to understand and complete study-related questionnaires |
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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 |
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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.
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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) |
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 or other specialty 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
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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 |
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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 | 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 | 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 | 12 |
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 |
Canada |
South Africa |
United States |
Estonia |
Germany |
Poland |
Romania |
United Kingdom |
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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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The end of the study for this study is defined as the last phone contact for the last patient. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 24 |
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 |