E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercalcemia of Malignancy (HCM) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020584 |
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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 |
This proof-of-concept study is designed to evaluate the potential for denosumab to treat HCM that does not respond to recent treatment with Intravenous (IV) bisphosphonates by lowering corrected serum calcium (CSC) ≤ 11.5 mg/dL (2.9 mmol/L) by study day 10 |
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E.2.2 | Secondary objectives of the trial |
- To determine the duration of the treatment effect - To determine the time to response - To determine the time to relapse - Changes in CSC level from baseline - To determine the safety of denosumab in this subject population |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Hypercalcemia of Malignancy (HCM) as defined as documented histologically or cytologically confirmed cancer and a CSC > 12.5 mg/dL (3.1 mmol/L) at screening by local laboratory - Last IV bisphosphonate treatment must be ≥ 7 days and ≤ 30 days before the screening CSC -Adults (≥ 18 years) -Adequate organ function as defined by the following criteria: - serum aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) - serum alanine aminotransferase (ALT) ≤ 5 x ULN - serum total bilirubin ≤ 2 x ULN -Before any study-specific procedure is performed, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
Evidence of hyperparathyroidism, hyperthyroidism, adrenal insufficiency, vitamin D intoxication, milk alkali syndrome, sarcoidosis, or other granulomatous disease Receiving dialysis for renal failure Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw Active dental or jaw condition which requires oral surgery Non-healed dental/oral surgery Planned invasive dental procedure over the course of the study Prior administration of denosumab Treatment with thiazides, calcitonin, mithramycin, and gallium nitrate within 7 days prior to the date of the screening CSC Treatment with cinacalcet within 4 weeks prior to the date of the screening CSC Thirty days or less since receiving an investigational product or device (ie, does not have marketing authorization; thalidomide use is allowed) in another clinical study Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products) Female subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment Subject (male or female) is not willing to use 2 highly effective methods of contraception during treatment and for 7 months (female) or 10 months (male) after the end of treatment Male subject with a pregnant partner who is not willing to use a condom during treatment and for additional 10 months after the end of treatment Subject will not be available for follow-up assessment. Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with a response, defined as CSC < or = 11.5 mg/dL (2.9 mmol/L), within 10 days after the first dose of denosumab. |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
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 | Information not present in EudraCT |
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 |
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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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La fine dello studio avverra` 4 settimane dopo l`ultima dose di denosumab. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |