Trial Outcomes & Findings for Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta (NCT NCT03638128)

NCT ID: NCT03638128

Last Updated: 2022-12-20

Results Overview

A Serious Adverse Event is defined as any untoward medical occurrence that met at least 1 of the following serious criteria: * Resulted in death (fatal) * Immediately life-threatening * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Other medically important serious event that may have jeopardized the participant or require medical or surgical intervention to prevent 1 of the outcomes listed above. Adverse events of special interest included hypocalcemia, hypersensitivity, bacterial cellulitis, osteonecrosis of the jaw (ONJ), hypercalcemia, and typical osteogenesis imperfecta (OI) femur fractures.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 75 participants
• Primary outcome timeframe: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
• Results posted on: 2022-12-20

Participant Flow

This study was conducted at 22 centers in North America, Europe, and Australia from July 2018 to March 2022. The study was an open-label extension of study 20130173 (NCT02352753). Participants who completed the end of study visit or who withdrew consent or assent to transition to every 3 months (Q3M) dosing regimen in Study 20130173 were offered participation in this study.

Participants who rolled over into Study 20170534 could continue to receive denosumab Q3M or could receive alternative osteoporosis medication, including commercial denosumab every 6 months (Q6M), or off-treatment observation only at the investigator's discretion. At any time during the study, participants could discontinue, resume, or initiate 1 of the above treatments based on the medical judgment of the investigator and per local standard of care.

Participant milestones

Measure	Alternative Medications / Observational Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Overall Study STARTED	21	27	27
Overall Study COMPLETED	5	8	1
Overall Study NOT COMPLETED	16	19	26

Reasons for withdrawal

Measure	Alternative Medications / Observational Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Overall Study Withdrawal by Subject	1	7	6
Overall Study Sponsor Decision	15	12	19
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta

Baseline characteristics by cohort

Measure	Alternative Medications / Observational n=21 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.	Total n=75 Participants Total of all reporting groups
Age, Continuous	12.5 years STANDARD_DEVIATION 3.5 • n=5 Participants	13.2 years STANDARD_DEVIATION 2.5 • n=7 Participants	14.3 years STANDARD_DEVIATION 4.8 • n=5 Participants	13.4 years STANDARD_DEVIATION 3.8 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	18 Participants n=7 Participants	14 Participants n=5 Participants	45 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	27 Participants n=7 Participants	24 Participants n=5 Participants	71 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	25 Participants n=7 Participants	23 Participants n=5 Participants	68 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.

Population: The safety analysis set includes all enrolled participants who provided informed consent/assent, had a non-missing enrollment date, and received at least 1 dose of denosumab during Study 20130173.

A Serious Adverse Event is defined as any untoward medical occurrence that met at least 1 of the following serious criteria:

• Resulted in death (fatal)
• Immediately life-threatening
• Required in-patient hospitalization or prolongation of existing hospitalization
• Resulted in persistent or significant disability/incapacity
• Was a congenital anomaly/birth defect
• Other medically important serious event that may have jeopardized the participant or require medical or surgical intervention to prevent 1 of the outcomes listed above.

Adverse events of special interest included hypocalcemia, hypersensitivity, bacterial cellulitis, osteonecrosis of the jaw (ONJ), hypercalcemia, and typical osteogenesis imperfecta (OI) femur fractures.

Outcome measures

Measure	Alternative Medications / Observational n=21 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Hypocalcemia	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Hypersensitivity	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Typical osteogenesis imperfecta femur fractures	2 Participants	1 Participants	2 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Positively adjudicated osteonecrosis of the jaw	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Any adverse event	18 Participants	22 Participants	19 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Serious adverse events	6 Participants	5 Participants	6 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Adverse events of special interest	5 Participants	5 Participants	9 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Hypercalcemia	3 Participants	4 Participants	9 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest Bacterial cellulitis (skin infection)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

Population: Safety analysis set participants who received at least one dose of denosumab in this study.

Blood samples were collected (from denosumab treated participants only) for the measurement of anti-denosumab binding antibodies. Samples positive for anti-denosumab binding antibodies were further tested for neutralizing antibodies.

Outcome measures

Measure	Alternative Medications / Observational n=27 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Anti-denosumab Antibodies Anti-denosumab binding antibodies	0 Participants	0 Participants	—
Number of Participants With Anti-denosumab Antibodies Anti-denosumab neutralizing antibodies	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

Population: Safety analysis set

Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. The grades refer to the severity of the finding:

Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant; Grade 4 = Life-threatening consequences, urgent intervention indicated.

Outcome measures

Measure	Alternative Medications / Observational n=21 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Clinical Laboratory Toxicities Grade ≥ 3	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

Population: Safety analysis set

Vital sign measurements included systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature. The investigator assessed vital sign results and determined whether any abnormal changes represented a clinically significant change from the participant's baseline values.

Outcome measures

Measure	Alternative Medications / Observational n=21 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Clinically Significant Vital Sign Findings	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, month 12 and month 24

Population: The metaphyseal analysis set includes participants with open growth plates and no hardware preventing accurate calculation of MI at baseline, and X-ray of the knee at baseline and postbaseline.

Anteroposterior radiographs of both knees (unless prohibited by the presence of hardware such as implants) were used to calculate the metaphyseal index Z-score of each knee in participants with open growth plates; the knee selected for assessment during the study was the knee with the higher Z-score at baseline. The metaphyseal index (MI) was calculated by the central imaging vendor as the ratio of femoral width over distal femoral growth plate width, and the Z-score for each participant, relative to the participant's age as:

MI Z-score = (participant value - mean)/SD, where mean and standard deviation (SD) are the corresponding values based on a reference population for the participant's age group at the time of the assessment.

Metaphyseal index Z-score above age-appropriate normal range is defined as a MI Z-score > 2.

Outcome measures

Measure	Alternative Medications / Observational n=3 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=4 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=4 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Metaphyseal Index Z-score Above Age-appropriate Normal Range Baseline	2 Participants	1 Participants	0 Participants
Number of Participants With Metaphyseal Index Z-score Above Age-appropriate Normal Range Month 12	2 Participants	1 Participants	0 Participants
Number of Participants With Metaphyseal Index Z-score Above Age-appropriate Normal Range Month 24	1 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline, month 12, and month 24

Population: Safety analysis set participants with radiologic assessments at each time point.

Participants underwent a visual inspection under natural light for the presence of the first and second molars. Participants were referred to a dentist to perform radiographic assessment of the unerupted molar(s) if:

• A participant was age 7 to 12 years and appeared to have an unerupted upper or lower first molar (ie, not all 4 first molars were visible/detectable).
• A participant was age 13 years or older and appeared to have an unerupted upper or lower (first or) second molar (ie, not all 4 first molars and all 4 second molars were visible/detectable).

Abnormal molar eruptions includes the number of participants 7 to 12 years of age with 1st unerupted or partially erupted molars and participants 13 years of age or older with 2nd unerupted or partially erupted molars.

Outcome measures

Measure	Alternative Medications / Observational n=19 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=22 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=17 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Number of Participants With Abnormal Molar Eruption of the First or Second Molar Based on Radiological Findings Baseline	2 Participants	3 Participants	1 Participants
Number of Participants With Abnormal Molar Eruption of the First or Second Molar Based on Radiological Findings Month 12	0 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Molar Eruption of the First or Second Molar Based on Radiological Findings Month 24	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline and month 12 and month 24

Population: Safety analysis set participants with radiologic assessments at baseline and each time point

Lateral cephalogram was performed to enable assessment of mandibular shaping. The lateral cephalogram is a profile X-ray of the skull and soft tissues and is used to assess the relation of the teeth in the jaws, the relation of the jaws to the skull, and the relation of the soft tissues to the teeth and jaws.

The following anatomical angles and dimensions were measured to evaluate the correct proportions of the mandible and its position relative to the skull/maxilla: Gonial angle; Sella-Nasion-A Point Angle (SNA angle); Sella-Nasion-B Point Angle (SNB angle); and A Point - Nasion-B Point Angle (ANB Angle).

Outcome measures

Measure	Alternative Medications / Observational n=10 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=15 Participants Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=1 Participants Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Percent Change From Baseline in Mandibular Shaping Parameters SNB angle: month 12	0.98 percent change Standard Deviation 1.56	1.75 percent change Standard Deviation 2.36	0.70 percent change
Percent Change From Baseline in Mandibular Shaping Parameters Gonial angle: month 12	0.5 percent change Standard Deviation 2.4	-1.4 percent change Standard Deviation 1.7	-1.0 percent change
Percent Change From Baseline in Mandibular Shaping Parameters Gonial angle: month 24	-2.1 percent change Standard Deviation 3.1	-1.4 percent change Standard Deviation 2.2	—
Percent Change From Baseline in Mandibular Shaping Parameters SNA angle: month 12	1.38 percent change Standard Deviation 2.09	0.37 percent change Standard Deviation 2.41	0.20 percent change
Percent Change From Baseline in Mandibular Shaping Parameters SNA angle: month 24	-0.07 percent change Standard Deviation 0.73	-1.70 percent change Standard Deviation 1.79	—
Percent Change From Baseline in Mandibular Shaping Parameters SNB angle: month 24	1.28 percent change	-1.60 percent change Standard Deviation 3.18	—
Percent Change From Baseline in Mandibular Shaping Parameters ANB angle: month 12	-81.06 percent change Standard Deviation 199.39	127.48 percent change Standard Deviation 312.99	-16.26 percent change
Percent Change From Baseline in Mandibular Shaping Parameters ANB angle: month 24	-79.69 percent change	15.65 percent change Standard Deviation 84.75	—

SECONDARY outcome

Timeframe: Baseline and months 6, 12, and 24

Population: The DXA analysis set includes all participants with baseline and ≥ 1 postbaseline valid DXA assessments for lumbar spine as provided by the central imaging vendor. BMD endpoints were pre-specified to be analyzed for combined treatment groups.

Bone densitometry assessments of the lumbar spine were performed using dual X-ray absorptiometry (DXA).

The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in lumbar spine BMD.

Outcome measures

Measure	Alternative Medications / Observational n=58 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score Month 6	-0.11 Z-score Standard Deviation 0.60	—	—
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score Month 12	-0.01 Z-score Standard Deviation 0.48	—	—
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score Month 24	0.21 Z-score Standard Deviation 0.49	—	—

SECONDARY outcome

Timeframe: Baseline, months 6, 12, and 24

Population: The DXA analysis set includes all participants with baseline and ≥ 1 postbaseline valid DXA assessments for the total hip as provided by the central imaging vendor. BMD endpoints were pre-specified to be analyzed for combined treatment groups.

Bone densitometry assessments of the hip were performed using dual X-ray absorptiometry (DXA).

The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in total hip BMD.

Outcome measures

Measure	Alternative Medications / Observational n=35 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Change From Baseline in Total Hip BMD Z-score Month 6	-0.07 Z-score Standard Deviation 0.40	—	—
Change From Baseline in Total Hip BMD Z-score Month 12	0.24 Z-score Standard Deviation 0.42	—	—
Change From Baseline in Total Hip BMD Z-score Month 24	0.50 Z-score Standard Deviation 0.54	—	—

SECONDARY outcome

Timeframe: Baseline and months 6, 12, and 24

Population: The DXA analysis set includes all participants with baseline and ≥ 1 postbaseline valid DXA assessments for the femoral neck as provided by the central imaging vendor. BMD endpoints were pre-specified to be analyzed for combined treatment groups.

Bone densitometry assessments of the femoral neck were performed using dual X-ray absorptiometry (DXA).

The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in femoral neck BMD.

Outcome measures

Measure	Alternative Medications / Observational n=35 Participants Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Change From Baseline in Femoral Neck BMD Z-score Month 6	0.08 Z-score Standard Deviation 0.44	—	—
Change From Baseline in Femoral Neck BMD Z-score Month 12	0.24 Z-score Standard Deviation 0.39	—	—
Change From Baseline in Femoral Neck BMD Z-score Month 24	0.45 Z-score Standard Deviation 0.58	—	—

Adverse Events

Alternative Medications / Observational

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Denosumab 1 mg/kg Q6M

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Denosumab 1 mg/kg Q3M

Serious events: 6 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alternative Medications / Observational n=21 participants at risk Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 participants at risk Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 participants at risk Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Gastrointestinal disorders Vomiting	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
General disorders Surgical failure	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Infections and infestations Appendicitis	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Femur fracture	9.5% 2/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Forearm fracture	9.5% 2/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Lower limb fracture	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Ulna fracture	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	18.5% 5/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Renal and urinary disorders Nephrolithiasis	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Respiratory, thoracic and mediastinal disorders Asthma	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.

Other adverse events

Measure	Alternative Medications / Observational n=21 participants at risk Participants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.	Denosumab 1 mg/kg Q6M n=27 participants at risk Participants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) administered by subcutaneous injection, but no Q3M denosumab during this study.	Denosumab 1 mg/kg Q3M n=27 participants at risk Participants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Gastrointestinal disorders Abdominal pain upper	9.5% 2/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
General disorders Pyrexia	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Infections and infestations COVID-19	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Ligament sprain	4.8% 1/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Metabolism and nutrition disorders Hypercalcaemia	14.3% 3/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	14.8% 4/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	18.5% 5/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Musculoskeletal and connective tissue disorders Arthralgia	28.6% 6/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	25.9% 7/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	14.8% 4/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Musculoskeletal and connective tissue disorders Back pain	14.3% 3/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	14.8% 4/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	11.1% 3/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 3/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	25.9% 7/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	0.00% 0/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Nervous system disorders Headache	14.3% 3/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	7.4% 2/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.
Renal and urinary disorders Hypercalciuria	52.4% 11/21 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	55.6% 15/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.	3.7% 1/27 • From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER