E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of denosumab on the reduction of radiographic erosive progression using GUSS™ (Ghent University Score System). |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of denosumab on the reduction of radiographic erosive progression as defined by diminishing the appearance of new erosive IP finger joints.
To assess the effect of denosumab on clinical variables, as well as ultrasonography and DEXA parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males and females 30 years of age.
• Subjects with hand OA having suffered from transient inflammatory attacks of the interphalangeal finger joints characteristic for what has been termed ‘inflammatory’ or ‘erosive’ hand OA.
• Subjects with hand OA showing inflammatory signs, either clinically or ultrasonographically, of the interphalangeal finger joints.
• Subjects with hand OA in which at least 1 interphalangeal finger joint has the typical appearance on the X-rays of a ‘J’ or ‘E’ phase joint as defined by the criteria mentioned above.
• Subjects with hand OA where at least 1 interphalangeal finger joint in the ‘J’ or ‘E’ phase presents a palpable swelling.
• Able and willing to give written informed consent and to comply with the requirements of the study protocol.
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E.4 | Principal exclusion criteria |
• Patients with known hypersensitivities to mammalian-derived drug preparations.
• Patients with clinically significant hypersensitivity to any of the components of Prolia.
• Current and/or Prior treatment with any investigational agent within 90 days, or five half-lives of the product, whichever is longer.
• Previous administration of denosumab from clinical trials or others (e.g. commercial use).
• Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Possibility of replenishment and re-screening.
• Subjects with current hypo- or hypercalcemia (normal serum calcium levels: 8.5-10.5 mg/dl or 2.12-2.62 mmol/L).
• Patients currently under bisphosphonate (BP) treatment or any use of oral BPs within 12 months of study enrollment or intravenous BPs or strontium ranelate within 5 years of study enrollment
• Prior use of any chondroprotective drug within 90 days e.g. chondroitin sulfate, glucosamine, avocado-soybean unsaponifiables, tetracyclins, corticosteroids.
• Prior use of any immunomodulating drug with possible effects on proinflammatory cytokine metabolism within 90 days a.o. corticosteroids, methotrexate, sulfasalazine, leflunomide, D-Penicillin, anti-malarials, cytotoxic drugs, TNF blocking agents.
• History of drug or alcohol abuse in the last year.
• Patients suffering from chronic inflammatory rheumatic disease (e.g. rheumatoid arthritis, spondylarthropathy, psoriatic arthritis, gout, chondrocalcinosis or other auto-immune diseases, e.g. systemic lupus erythematosus).
• History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years.
• History of any Solid Organ or Bone Marrow Transplant.
• Comorbidities: significant renal function impairment (glomerular filtration < 30 ml/min/1.73m2 or <50% of normal value), uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), uncontrolled hypo or hyperparathyroidism, active inflammatory bowel disease, malabsorption, liver failure or chronic hepatic disease (serum AST/ALT levels 3 times above normal), recent stroke (within three months), chronic leg ulcer and any other condition (e.g,. indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the protocol.
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures .
• Patient who is pregnant or planning pregnancy; if the female subject is of child-bearing age, she must use a valid mean of contraception during the study and for 9 months after last dose of study medication. For males with a partner of childbearing potential: subject refuses to use 1 effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
• Female subjects who are breast-feeding.
• History of osteonecrosis of the jaw, and/or recent (within 3 months) tooth extraction or other unhealed dental surgery; or planned invasive dental work during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
the change in the negative evolution in GUSS™ scores in the target IP joints |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline to week 24. |
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E.5.2 | Secondary end point(s) |
1. the changes in the negative evolution of GUSS™ scores in the target IP joints
2. Changes in clinical and patient recorded outcome measures The following outcome measures will be recorded: AUSCAN (AUStralian CANadian Osteoarthritis Hand Index), FIHOA (Functional Index of Hand Osteoarthritis), Pain on VAS scale, consumption of analgesics (paracetamol)/NSAIDs to be recorded by each patient on a diary, tenderness upon pressure, diameter of selected target joints, and grip strength of both hands.
3. Changes in sonographic inflammatory signals. Inflammatory changes will be assessed by measuring the amount of effusion and Power Doppler signal (scoring on a semi-quantitative scale).
4. Effect of denosumab on bone mass densitometry score in this group of patients compared to placebo. Changes from baseline (day 1) in T-score at lumbar spine and hip measured by bone densitometry at week 48 after administration of denosumab compared to placebo.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from week 24 to week 48 and from baseline to week 48.
2. from baseline (day 1) to week 48 after administration of denosumab compared to placebo.
3. from baseline at week 12 and 48.
4. from baseline to week 48 |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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) | 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 | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 42 |
E.8.9.1 | In the Member State concerned days | |