E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bone Loss in Subjects Undergoing Androgen-Deprivation Therapy (ADT) for Non-metastatic Prostate Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065687 |
E.1.2 | Term | Bone loss |
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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 |
To assess the effect of denosumab on cataract event development or progression by month 12 based on a change of ≥ 1.0 in posterior subcapsular (P), ≥ 1.0 in cortical (C), or ≥ 0.7 in nuclear opalescence (NO) using the Lens Opacities Classification System III (LOCS III) score. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of denosumab on cataract event development or progression by month 12 based on a change of ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO using the LOCS III score To assess the effect of denosumab on cataract event development or progression by month 6 based on LOCS III scores To assess the effect of denosumab on confirmed cataract event development or progression by month 12 based on LOCS III scores To assess the effect of denosumab on the incidence of decreased best corrected visual acuity (BCVA) from the baseline BCVA on the ETDRS (“Early Treatment Diabetic Retinopathy Study”) charts To assess the effect of denosumab on change in refraction needed to achieve BCVA To describe the safety of denosumab administration as measured by adverse events and safety laboratory parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men ≥ 30 of age with non-metastatic prostate cancer
Have undergone bilateral orchiectomy or initiated ADT with GnRH agonists and is expected to continue on ADT for at least 12 months
ECOG score (0, 1, or 2)
Baseline BCVA of 20/40, (6/12 or 0.5 on the decimal scale) or better using the ETDRS charts at 4 meters in one eye with a natural, intact lens
Bone Mineral Density (BMD) requirements: • If < 70 years: BMD T-score at the lumbar spine, total hip, or femoral neck ≥ -2.5 and ≤ -1.0 (“osteopenia”; at least one site required). • If ≥ 70 years: BMD T-score at lumbar spine and total hip and femoral neck ≥ -2.5 • At least 2 evaluable lumbar vertebrae
Signed informed consent |
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E.4 | Principal exclusion criteria |
Screening LOCS III grade of ≥ 3.5 for P, ≥ 4.0 for C, or ≥ 4.5 for NO
Bone Mineral Density (BMD) T-score < -2.5 at lumbar spine and/or total hip and/or femoral neck (“osteoporosis”)
Known history of prior fragility fracture (fractures associated with no or minimal trauma severity [eg, fall from standing height])
Evidence of distant metastases
Diagnosis of any secondary non-prostate malignancy within 5 years of randomization, except for adequately treated basal cell or squamous cell skin cancer
Known HIV, HCV, or Hepatitis B Infection
Known osteonecrosis of the jaw (ONJ)
Current hyper-or hypothyroidism (stable on thyroid replacement therapy is allowed, if the TSH is within the normal range)
Paget’s disease, Cushing’s disease, hyperprolactinemia, chronic liver disease or rheumatoid arthritis
Dialysis or expected to undergo dialysis within 1 year
Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before randomization
Major surgery, or significant traumatic injury occurring within 4 weeks before randomization
Incisional eye surgery in both eyes or cataract surgery in both eyes
Ocular disease leading to visual loss (eg, macular degeneration, glaucoma, corneal disease) that would make assessment of visual status difficult.
Planned cataract surgery or major visual disturbance expected to result in need for cataract surgery within one year
Concurrent systemic anti-neoplastic therapy or radiotherapy, other than ADT and/or anti-androgen therapy
Current administration of IV bisphosphonates (oral bisphosphonates allowable if they are stopped at study entry)
Concurrent use of anti-glaucoma medications
Concurrent chronic corticosteroid therapy or pulse corticosteroid therapy including ophthalmologic steroid use (topical, inhaled, or nasal steroids are allowed)
Incapable of being responsive to midriatic agents (minimum of approximately a 6 mm pupil required)
Prior administration of denosumab
PSA > 5 ng/mL at screening
Serum calcium or albumin-adjusted serum calcium levels < 2.0 mmol/L (8.0 mg/dL), or ≥ 2.9 mmol/L (11.5 mg/dL)
25-hydroxyvitamin D deficiency (< 20 ng/mL)
Not willing to use 2 highly effective methods of contraception during treatment and for 10 months after the end of treatment
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
Is currently enrolled in the active treatment phase of a study investigating an unapproved product or device, or has been treated within the last 30 days with an unapproved product or device. Subjects in the observational phase of clinical studies (eg, to collect survival data) are allowed
Organic or psychiatric disorder which, in the opinion of the investigator may 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) |
Subject incidence of cataract event development or progression by month 12, based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score. |
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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 | Yes |
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) | 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 | 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.8.3 |
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 | 25 |
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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End-of-study will occur when the last subject has completed their month 12 visit or has withdrawn from the study. |
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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 | |
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 | 7 |