A Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy

• Register: EUCTR
• Last refreshed on: 22 August 2016
• Main ID: EUCTR2009-012076-26-PL
• Date of registration: 22/09/2009
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy
• Scientific title: A Double-blind, Placebo-controlled Study to Evaluate New or Worsening Lens Opacifications in Subjects with Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss due to Androgen-Deprivation Therapy
• Date of first enrolment: 21/06/2012
• Target sample size: 760
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012076-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Canada, Czech Republic, European Union, France, Greece, Hungary, India, Latvia, Mexico, New Zealand, Poland, Russian Federation, Slovakia, Slovenia, South Africa, Ukraine, United States

Contacts

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

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)

Screening 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 133
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 627

Exclusion criteria:
Screening LOCS III grade in both eyes 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)

Maximal pupil dilation size <6.0 mm

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)

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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Androgen-dependent non-metastatic prostate cancer and therapy-induced bone loss
MedDRA version: 17.1 Level: PT Classification code 10065687 Term: Bone loss System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 17.1 Level: LLT Classification code 10036910 Term: Prostate cancer NOS System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Prolia
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: Immunoglobulin G2 Human Monoclonal Antibody to RANK Ligand
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To assess the effect of denosumab on lens opacification 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.

Secondary Objective: • To assess the effect of denosumab on lens opacification 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 lens opacification event development or progression by month 6 based on LOCS III scores
• To assess the effect of denosumab on confirmed lens opacification 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

Timepoint(s) of evaluation of this end point: Month 12

Primary end point(s): Subject incidence of lens opacification 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

Secondary Outcome(s)

Secondary end point(s): 1-Subject incidence of lens opacification 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 in the LOCS III score
2-Subject incidence of lens opacification event development or progression by month 6, based on a change of = 1.0 in P, = 1.0 in C, or = 0.7 in NO in the LOCS III score
3- Subject incidence of confirmed lens opacification 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. A confirmed lens opacification event development or progression is defined as two directly subsequent events per protocol assessments at the same location (P, C, NO) using LOC III as above.
4- Subject incidence of a decrease from baseline in BCVA as measured by a change of = 10 letters on the ETDRS at 4 meters, at months 3, 6, 9, and 12
5- Change in refraction needed to achieve BCVA at 3, 6, 9, and 12 as measured by change in sphere
6- Adverse event incidence, serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry)

Timepoint(s) of evaluation of this end point: 1- Month 12
2- Month 6
3- Month 12
4- Months 3, 6, 9, and 12
5- Months 3, 6, 9, and 12
6- Month 12

Secondary ID(s)

2009-012076-26-FR

NCT00925600

20080560

Source(s) of Monetary Support

Amgen Inc