E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pain due to osteoarthritis and chronic lower back pain |
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E.1.1.1 | Medical condition in easily understood language |
Chronic pain of the lower back and 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 | 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 | 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 in relieving CLBP as compared to placebo in patients with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip when treated for up to 16 weeks. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: -To evaluate the safety and tolerability of fasinumab compared to placebo when patients with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks -To characterize the concentrations of fasinumab in serum over time when patients with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks -To evaluate the immunogenicity of fasinumab when treated for up to 16 weeks in patients with a clinical diagnosis of moderate-to-severe non-radicular CLBP and 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 |
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E.3 | Principal inclusion criteria |
A patient must meet the following criteria to be eligible for inclusion in the study: 1. Male and female patients ≥18 years of age at screening visit 2. Body mass index ≤39 at screening visit 3. Clinical diagnosis of non-radicular moderate-to-severe CLBP for ≥3 months (prior to screening visit) as defined by the following: a. Quebec taskforce category 1 (pain without radiation) or 2 (pain with proximal radiation above the knee), and b. Primary pain between 12th thoracic vertebra and lower gluteal folds, and c. At both screening and randomization visit, a LBPI NRS score ≥4 over previous 24 hours, and d. Mean daily LBPI score ≥4 during pre-randomization period, and e. PGA of LBP of fair, poor, or very poor at screening visit 4. Clinical diagnosis of OA in at least 1 hip or knee joint based on the American College of Rheumatology Criteria with radiographic evidence of OA (K-L ≥2) at screening as described in Section 8.2.1.8 5. History of inadequate relief of CLBP from non-pharmacologic therapy (eg, exercise, physical therapy, acupuncture, or multidisciplinary rehabilitation) 6. History of inadequate pain relief or intolerance to analgesics used for CLBP defined by: a. Inadequate pain relief from paracetamol/acetaminophen, and b. Intolerance or inadequate pain relief from at least 1 oral NSAID, and c. Intolerance or inadequate pain relief from at least 1 opioid or tramadol, unwillingness to take opioid therapy for a medically acceptable reason, or lack of access to opioid therapy 7. History of regular use of analgesic medications for LBP pain (defined as an average of 4 days per week over the 4 weeks prior to the screening visit), including NSAIDs, selective cyclooxygenase 2 inhibitors, opioids, paracetamol/acetaminophen, or combinations thereof 8. 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 (countries where 500 mg strength tablets/capsules are available) or 2600 mg (countries where 325 mg strength tablets/capsules are available) 9. Willing to maintain current activity and exercise levels throughout the study 10. Willing to undergo joint replacement (JR) surgery, if necessary 11. 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 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. Provide signed informed consent 14. Able to understand and complete study-related questionnaires
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E.4 | Principal exclusion criteria |
Key exclusion criteria: 1. Non-compliance with the LBPI NRS data entries during the pre-randomization period, as defined by more than 2 missing entries 2. History of Quebec taskforce category >2 (pain with proximal radiation above the knee) lumbosacral radiculopathy within the past 2 years prior to the screening visit 3. Patient is not a candidate for MRI 4. Evidence on baseline lumbar spine MRI (or lumbar X-ray, if requested) of severe spinal stenosis, disc herniation with substantial nerve compression, recent vertebral fracture, an active destructive process or marked segmental instability (eg, severe scoliosis, bone marrow edema, or Modic type 1 change) 5. History of major trauma or back surgery in the past 6 months prior to the screening visit 6. History or presence of pyriformis syndrome 7. Current or pending worker’s compensation, litigation, disability, or any other monetary settlement related to LBP 8. History or presence on imaging of arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), recent fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation (prosthetic hip dislocation is eligible), knee dislocation (patella dislocation is eligible), congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas, or pathological fractures during the screening period 9. History or presence at the screening visit of non-OA inflammatory joint disease (eg, rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-gout, gout, spondyloarthropathy, joint infections within the past 5 years, Paget’s disease of the spine, pelvis, or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy) 10. History of hospital admission for depression or suicide attempt within 2 years or active, severe major depression at screening 11. Beck Depression Inventory - II (BDI-II) score ≥29 at screening 12. Use of a monoamine reuptake inhibitor, tricyclic antidepressants, selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors for treatment of CLBP within 4 weeks prior to the screening visit 13. Use of extended-release or controlled-release opioids (eg, oxycontin), transdermal fentanyl or methadone within 3 months prior to the screening visit 14. Use of opioids with a morphine equivalent dose of ≥30 mg per day for more than 4 days per week 15. Use of systemic (ie, oral or intramuscular) corticosteroids or intra-articular corticosteroids in any joint within 30 days prior to the screening visit (topical, intranasal, and inhaled corticosteroids are permitted) 16. Epidural steroid injections within 3 months prior to the screening visit 17. Botox injections for LBP within 6 months prior to the screening visit 44. Pregnant or breastfeeding women 45. Women of childbearing potential (WOCBP)* who have a positive pregnancy test result or do not have their pregnancy test result at baseline 46. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 20 weeks after the last dose.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change in the daily average LBPI NRS score from baseline to week 16 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) |
The secondary endpoints of the study are: -Change from baseline to week 16 in RMDQ total score in patients treated with fasinumab compared to patients treated with placebo - Change from baseline to week 16 in Patient Global Assessment (PGA) of LBP score in patients treated with fasinumab compared to patients treated with placebo -Proportion of patients who are responders as defined by ≥30% reduction from baseline to week 16 in daily average LBPI NRS score in patients treated with fasinumab compared to patients treated with placebo -Change from baseline to week 16 in the Brief Pain Inventory Short Form (BPI-sf) pain interference score in patients treated with fasinumab compared to patients treated with placebo
The safety endpoints in this study are: -Incidence of AA (as confirmed by an independent adjudication committee) -Incidence of DA (as confirmed by an independent adjudication committee) -Incidence of treatment-emergent adverse event (TEAEs) - Incidence of SNS dysfunction (as diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist) - Incidence of peripheral sensory AEs that require a neurology consultation -Incidence of all-cause joint replacement (JR) surgeries through week 16 and through the end of follow-up period (week 36) -Incidence of JRs at telephone survey approximately 52 weeks after last dose of study drug |
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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 | 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 | No |
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) | 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 | 2 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Czech Republic |
Hungary |
Poland |
Romania |
South Africa |
Spain |
United Kingdom |
United States |
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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. The last phone contact will be conducted approximately 52 weeks following the last dose of study drug |
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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 | 7 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |