| 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 | 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 |
|
| 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 |
|
| 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 with placebo, when administered for up to 16 weeks in patients with OA of the knee or hip. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
1. To evaluate the efficacy of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip
2. To evaluate the efficacy of fasinumab compared with placebo, when administered for up to 52 weeks in patients with pain due to OA of the knee or hip
3. To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip
4. To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 52 weeks in patients with pain due to OA of the knee or hip
5. To evaluate the pharmacokinetic (PK) profile of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks
6. To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks
|
|
| 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 |
A patient must meet the following criteria to be eligible for inclusion in the study:
1. Male and female patients, at least 18 years of age, at screening
2. 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
3. Moderate to severe pain in the index joint defined at both the screening and randomization visits
4. 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)
5. 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, as defined by
a. Inadequate pain relief from acetaminophen/paracetamol AND
b. Intolerance to or inadequate pain relief from at least 1 opioid or tramadol, unwillingness to take opioid or tramadol therapy for a medically acceptable reason, or lack of access to an opioid or to tramadol
6. Currently using a stable dose of NSAID, defined as using NSAIDs for approximately 4 days per week over the last 4 weeks
7. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the initial 16 weeks of treatment
8. Stable treatment with glucosamine sulfate and chondroitin sulfate treatments must be stopped during the pre-randomization period
9. 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
10. Willing to maintain current activity and exercise levels throughout the study
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. Able to understand and complete study-related questionnaires
|
|
| E.4 | Principal exclusion criteria |
A patient who meets any of the following criteria will be excluded from the study:
1. Non-compliance with the NRS recording during the pre-randomization period (4 or more
consecutive missed diary entries)
2. 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
3. History or presence on imaging of arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), neuropathic joint arthropathy, hip dislocation (prosthetic hip dislocation is eligible), knee dislocation (patella dislocation is eligible), extensive subchondral cysts, significant bone collapse, significant bone loss, 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 visit
6. Patient is not a candidate for 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 one eventually became necessary
8. History or presence at the screening visit of autonomic neuropathy, diabetic neuropathy,
or other peripheral neuropathy, including reflex sympathetic dystrophy
9. History or diagnosis of chronic autonomic failure syndrome including pure autonomic
failure, multiple system atrophy (Shy-Drager syndrome)
10. History of naproxen intolerance, or existence of a medical condition (eg, high risk of GI
bleed, previous ulcer, use of anti-coagulants, or the use of concomitant medication for which naproxen is contraindicated
11. Known allergy or sensitivity to doxycycline or related compounds, or monoclonal
antibodies
12. Poorly controlled diabetes (defined as any single value of hemoglobin A1c [HbA1c]
>9.0%) at the screening visit
13. Known history of human immunodeficiency virus infection
14. Known history of ocular herpes simplex virus, herpes simplex virus pneumonia, or herpes
simplex virus encephalitis
15. History of sickle cell disease, including sickle cell anemia and β-thalassemia
16. Confirmed elevated screening alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) ≥2.5 times the upper limit of normal (ULN)
17. Resting heart rate of <50 beats per minute (bpm) or >100 bpm (by vital sign assessment
or as captured during electrocardiogram [ECG] assessment) at the screening or
randomization visits
18. History or presence of 2nd or 3rd degree heart block, 1st degree heart block with abnormal
QRS complex, or bifascicular block by ECG assessment at the screening visit
19. History or presence of orthostatic hypotension, as defined in Section 8.2.3.4, at the
screening, pre-randomization, or randomization visits
20. History of poorly controlled hypertension, as defined by:
a. Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at
the screening visit
b. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure
of 100 mm Hg to 109 mm Hg at the screening visit, AND a history of end-organ
damage (including history of left ventricular hypertrophy, heart failure, angina,
myocardial infraction, stroke, transient ischemic attack, peripheral arterial disease
and moderate to advanced retinopathy [hemorrhages or exudates, papilledema])
21. Congestive heart failure with NY Heart Classification of stage III or IV (Dolgin 1994)
22.Transient ischemic attack or cerebrovascular accident within the past 12 months prior to
the screening visit, or myocardial infarction, or acute coronary syndromes within the past
6 months prior to the screening visit |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Change in the WOMAC pain subscale scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo.
2. Change in the WOMAC physical function subscale scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The key secondary endpoints of the study are:
1. Change in the Patient Global Assessment (PGA) scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo
2. Percentage of patients treated with fasinumab, compared with that of patients treated with placebo, who had a response at week 16, with response defined as an improvement by ≥30% in the WOMAC pain subscale scores
3. Change in WOMAC pain subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen
4. Change in WOMAC physical function subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen
5. Change in WOMAC pain subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo
6. Change in WOMAC physical function subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo
7. Change in the PGA scores from baseline to week 52 in patients treated with fasinumab compared with that of patients treated with placebo
8. Change in the PGA scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with naproxen
The safety endpoints in this study are:
1. Incidence of severe adjudicated arthropathy (AA) (as confirmed by adjudication)
2. Incidence of treatment-emergent adverse events (TEAEs)
3. Incidence of AA (as confirmed by adjudication)
4. Incidence of sympathetic nervous system dysfunction (as diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist)
5. Incidence of all-cause joint replacements through week 52 and through the follow-up period
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | 5 |
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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 |
| South Africa |
| United States |
| Lithuania |
| Poland |
| Bulgaria |
| Romania |
| Spain |
| Germany |
| Denmark |
| Hungary |
| Russian Federation |
| Ukraine |
| United Kingdom |
|
| 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 study is defined as the last phone contact of the last patient in this study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
