Evaluation of New or Worsening Lens Opacifications in Men With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss

• ClinicalTrials.gov Identifier: NCT00925600
• Recruitment Status: Completed
• First Posted: June 22, 2009
• Results First Posted: May 30, 2017
• Last Update Posted: May 30, 2017
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 18, 2009
• First Posted Date: June 22, 2009
• Results First Submitted Date: April 19, 2017
• Results First Posted Date: May 30, 2017
• Last Update Posted Date: May 30, 2017
• Actual Study Start Date: November 30, 2009
• Actual Primary Completion Date: May 12, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2017)

Percentage of Participants With Lens Opacification Event Development or Progression by Month 12 [ Time Frame: 12 months ]

The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.

• Original Primary Outcome Measures (submitted: June 18, 2009): Subject incidence of cataract event development or progression by month 12 exceeding a predefined level at any of 3 key lens locations using LOCS III score. [ Time Frame: one year ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: June 18, 2009)

• Subject incidence of cataract event development or progression by month 6 exceeding a predefined level at any of 3 key lens locations using LOCS III score. [ Time Frame: One year ]
• Adverse event incidence and changes in safety analytes. [ Time Frame: One year ]

Current Other Pre-specified Outcome Measures (submitted: April 19, 2017)

• Percentage of Participant With 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 [ Time Frame: 12 months ]
  The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III score from baseline.
• Percentage of Participants With Lens Opacification Event Development or Progression by Month 6 [ Time Frame: 6 months ]
  The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 6 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.
• Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12 [ Time Frame: 12 months ]
  The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline. A confirmed lens opacification event development or progression was defined as 2 directly subsequent events per protocol assessments at the same location (P, C, NO) using LOCS III as above.
• Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters [ Time Frame: Baseline and Months 3, 6, 9 and 12 ]
  The best corrected visual acuity (BCVA) is the best vision one can achieve with correction (such as eye glasses) as measured on an eye chart. BCVA was assessed by a trained ophthalmologist using the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at 4 meters. The modified University of Crete ETDRS chart was used in Ukraine, Greece, Russia and Bulgaria, which do not use the Roman alphabet. The 2000 series revised ETDRS chart was used to assess the change in all other countries. The letter score was calculated based on the number of letters that were correctly identified; higher letter scores correspond to better visual acuity.
• Change From Baseline in Refraction Needed to Achieve BCVA [ Time Frame: Baseline and months 3, 6, 9, and 12 ]
  Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.
• Number of Participants With Adverse Events [ Time Frame: 12 months ]
  Adverse events (AEs) were assessed for severity by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) severity grading scale, version 3.0, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 =Life-threatening AE and Grade 5 = Death due to AE. Treatment-related AEs (TRAEs) include only events for which the investigator indicated there was a reasonable possibility they may have been caused by the study drug.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of New or Worsening Lens Opacifications in Men With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss
• Official 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
• Brief Summary: This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate new or worsening lens opacifications in men with non-metastatic prostate cancer receiving denosumab for bone loss due to androgen deprivation therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Supportive Care

Condition

• Cancer
• Cataract
• Low Bone Mineral Density
• Osteopenia
• Osteoporosis
• Prostate Cancer

Intervention

• Biological: Denosumab
  Prefilled syringe for subcutaneous (SC) injection administered at a dose of 60 mg
  Other Name: Prolia®
• Biological: Placebo
  Prefilled syringe for subcutaneous (SC) injection

Study Arms

• Placebo Comparator: Placebo
  Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
  Intervention: Biological: Placebo
• Experimental: Denosumab
  Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
  Intervention: Biological: Denosumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 19, 2017): 769
• Original Estimated Enrollment (submitted: June 18, 2009): 760
• Actual Study Completion Date: May 12, 2016
• Actual Primary Completion Date: May 12, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men ≥ 30 years of age with non-metastatic prostate cancer, having undergone bilateral orchiectomy or initiated androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and is expected to continue on ADT for at least 12 months
• Adequate visual accuracy allowing eye testing
• Bone Mineral Density (BMD) requirements: Osteopenia if under 70 years of age; Osteopenia or normal BMD if over 70 years of age
• Signed informed consent

Exclusion Criteria:

• Previous surgery for cataracts in both eyes, current diagnosis of cataracts, cataracts surgery foreseen in the near future, or ocular disease leading to visual loss
• Diagnosis of osteoporosis

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 30 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bulgaria, Canada, Czechia, France, Greece, Hungary, India, Latvia, Mexico, New Zealand, Poland, Russian Federation, Slovakia, Slovenia, South Africa, Ukraine, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00925600
• Other Study ID Numbers: 20080560; 2009-012076-26 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Global Development Leader, Amgen Inc.
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: April 2017