Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Eye Diseases

Prostatic Neoplasms

Osteoporosis

Cataract

Bone Diseases

Bone Diseases, Metabolic

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Lens Diseases

Metabolic Diseases

All Drugs and Chemicals

Bone Density Conservation Agents

Androgens

Denosumab

Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.

Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.

Prefilled syringe for subcutaneous (SC) injection administered at a dose of 60 mg

Prefilled syringe for subcutaneous (SC) injection

Placebo

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.

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

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

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.

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.

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.

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.

Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.

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.

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.

Amgen

All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group received at least 1 dose of denosumab in error, and are included in the denosumab group for safety.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Participants randomized to receive placebo administered by subcutaneous injection on Day 1 and at Month 6.

Participants randomized to receive denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.

Total

Age, Continuous

18 - 64 years

65 - 74 years

75 - 84 years

≥ 85 years

Age, Customized

Sex: Female, Male

White

Black (or African American)

Hispanic/Latino

Other

Asian

Japanese

Native Hawaiian or Other Pacific Islander

Race/Ethnicity, Customized

Presence of Cataract(s)

Presence of Diabetes

Received Androgen-deprivation Therapy (ADT)

Orchiectomy (Surgical Castration)

< 3.0 at all sites [P, C, and NO]

≥ 3.0 at any of these sites

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.

Screening Lens Opacities Classification System (LOCS) III Status

Participant-reported history of cataracts was a study stratification factor.

Participant-reported History of Cataract

Study Director

The primary endpoint was summarized with the point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (\< 3.0 at all sites \[P, C, and NO\] vs. ≥ 3.0 at any of these sites), age group (\< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).

The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who received ≥ 1 dose of denosumab in error are analyzed in the denosumab group.

Percentage of Participants With Lens Opacification Event Development or Progression by Month 12

The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (\< 3.0 at all sites \[P, C, and NO\] vs. ≥ 3.0 at any of these sites), age group (\< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).

The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who eceived ≥ 1 dose of denosumab in error are analyzed in the denosumab group.

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

Lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site at or before month 6. Three participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.

Percentage of Participants With Lens Opacification Event Development or Progression by Month 6

Lens opacification analysis set with at least two post-baseline LOCS III measurements by month 12.

Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.

Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12

Month 3 (n = 372, 375)

Month 6 (n = 355, 357)

Month 9 (n = 350, 346)

Month 12 (n = 343, 342)

Lens opacification analysis set with evaluable assessments at both baseline and the time point of interest in the same eye (as indicated by "n"). Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.

Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters

Month 3 (n = 362, 358, 358, 359)

Month 6 (n = 347, 343, 341, 344)

Month 9 (n = 341, 339, 332, 332)

Month 12 (n = 336, 334, 328, 329)

Participants received placebo subcutaneous injection on Day 1 and at Month 6.

Placebo - Left Eye

Placebo - Right Eye

Denosumab - Right Eye

Lens opacification analysis set with evaluable assessments at both baseline and each time point in the same eye.

n=the number of evaluable eyes in the lens opacification analysis set at the corresponding time point; 3 participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.

Change From Baseline in Refraction Needed to Achieve BCVA

Any adverse event

Serious adverse events

AE leading to discontinuation of study drug

AE leading to discontinuation from study

Fatal adverse events

AE grade 3, 4, or 5

Treatment-related adverse events

Serious treatment-related adverse events

TRAE leading to discontinuation of study drug

TRAE leading to discontinuation from study

Fatal treatment-related adverse events

TRAE grade 3, 4, or 5

All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group who received at least 1 dose of denosumab in error are analyzed in the denosumab group for safety.

Spots Global Cancer Trial Database for lens opacification