Trial Outcomes & Findings for Long-term Safety Follow-up of Subjects With Giant Cell Tumor of Bone Treated With Denosumab in Study 20062004 (NCT NCT03301857)

Last Updated: 2024-05-20

Results Overview

EOIs assessed in the study were signs and symptoms of osteonecrosis of the jaw (ONJ), malignancy (including malignancy in GCTB), atypical femoral fracture (AFF), hypocalcemia, hypercalcemia after treatment discontinuation, pregnancy and lactation (if occurring during treatment or within 5 months of the last dose of denosumab). Hypocalcemia includes events that occurred after 30 days following the last dose of IP and includes TEAEs only. Other EOIs encompass all events from signing the informed consent to the end of the study (approximately 5 years). ONJ and AFF events were adjudicated by independent reviewers.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

85 participants

Primary outcome timeframe

Up to approximately 5 years

Results posted on

2024-05-20

Participant Flow

Participants with giant cell tumor of bone (GCTB) were enrolled across 8 countries (Australia, Italy, France, Poland, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States) between November 2017 and July 2023.

Participants in the study were enrolled upon completing study 20062004.

Participant milestones

Participant milestones
Measure	Exposed to Investigational Product (IP) Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg every 4 weeks \[Q4W\] subcutaneous injection \[SC\]) and schedule at the investigator's discretion.	Not Exposed to IP Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Overall Study STARTED	51	34
Overall Study Received Denosumab	51	0
Overall Study COMPLETED	29	26
Overall Study NOT COMPLETED	22	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Exposed to Investigational Product (IP) Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg every 4 weeks \[Q4W\] subcutaneous injection \[SC\]) and schedule at the investigator's discretion.	Not Exposed to IP Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Overall Study Death	0	2
Overall Study Lost to Follow-up	4	2
Overall Study Decision by Sponsor	6	0
Overall Study Withdrawal by Subject	12	4

Baseline Characteristics

Long-term Safety Follow-up of Subjects With Giant Cell Tumor of Bone Treated With Denosumab in Study 20062004

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exposed to IP n=51 Participants Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg Q4W SC) and schedule at the investigator's discretion.	Not Exposed to IP n=34 Participants Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.	Total n=85 Participants Total of all reporting groups
Age, Continuous	42.4 Years STANDARD_DEVIATION 12.8 • n=93 Participants	46.7 Years STANDARD_DEVIATION 15.1 • n=4 Participants	44.1 Years STANDARD_DEVIATION 13.9 • n=27 Participants
Sex: Female, Male Female	32 Participants n=93 Participants	23 Participants n=4 Participants	55 Participants n=27 Participants
Sex: Female, Male Male	19 Participants n=93 Participants	11 Participants n=4 Participants	30 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=93 Participants	10 Participants n=4 Participants	23 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=93 Participants	24 Participants n=4 Participants	62 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized White	35 Participants n=93 Participants	31 Participants n=4 Participants	66 Participants n=27 Participants
Race/Ethnicity, Customized Other	10 Participants n=93 Participants	0 Participants n=4 Participants	10 Participants n=27 Participants
Race/Ethnicity, Customized Black (or African American)	4 Participants n=93 Participants	3 Participants n=4 Participants	7 Participants n=27 Participants
Race/Ethnicity, Customized Asian	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.

Outcome measures

Outcome measures
Measure	Exposed to IP n=51 Participants Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg Q4W SC) and schedule at the investigator's discretion.	Not Exposed to IP n=34 Participants Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Adjudicated positive ONJ	3 Count of Participants	0 Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Malignancy, including malignancy in GCTB	6 Count of Participants	1 Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Adjudicated positive AFF	2 Count of Participants	0 Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Hypocalcemia	3 Count of Participants	0 Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Hypocalcemia after treatment end	0 Count of Participants	0 Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) Pregnancy and lactation	0 Count of Participants	0 Count of Participants

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.

An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. An AE is considered as treatment-emergent if the AE occurs during the time period from the first dose of IP in this study through last dose of IP plus 30 days. TEAEs related to IP include only TEAEs for which the Investigator indicated there was a reasonable possibility they may have been caused by IP. AEs were graded (grade 3 \[severe or medically significant but not immediately life-threatening\], 4 \[life-threatening\], and 5 \[death related to the AE\]) using the Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Outcome measures
Measure	Exposed to IP n=51 Participants Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg Q4W SC) and schedule at the investigator's discretion.	Not Exposed to IP Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) Fatal TEAEs	0 Count of Participants	—
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) TEAEs leading to IP discontinuation	9 Count of Participants	—
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) All TEAEs related to IP	14 Count of Participants	—
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) CTCAE Grade 3, 4, or 5	16 Count of Participants	—
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) All TEAEs	47 Count of Participants	—
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) Serious TEAEs	8 Count of Participants	—

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study. The number of participants analyzed is inclusive of participants with available data.

Disease progression or recurrence is defined as the best post-baseline response of progressive disease (PD) without any post-baseline complete response (CR) /partial response (PR) /stable disease (SD) or a post-baseline response of PD following a post-baseline CR/PR/SD. PD is defined as the response of progressive disease, locally recurrent disease or distant recurrence. CR is defined as no evidence of disease following surgical resection while on study 20062004. PR is defined as no new lesion or disease progression while enrolled in study 20062004. SD is defined as local disease progression/recurrence or distant metastatic disease while on study 20062004.

Outcome measures

Outcome measures
Measure	Exposed to IP n=50 Participants Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg Q4W SC) and schedule at the investigator's discretion.	Not Exposed to IP n=33 Participants Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Number of Participants With Disease Progression or Recurrence of GCTB	5 Count of Participants	3 Count of Participants

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.

GCTB interventions include: surgery, chemotherapy, embolization, interferon, and radiotherapy.

Outcome measures

Outcome measures
Measure	Exposed to IP n=51 Participants Participants who received denosumab at the conclusion of study 20062004 continued in this study (study 20140114), and received denosumab at the current dose (120 mg Q4W SC) and schedule at the investigator's discretion.	Not Exposed to IP n=34 Participants Participants who completed denosumab treatment in study 20062004 and were in the safety follow up at the conclusion of study 20062004 continued in long term safety follow up in this study (study 20140114), and did not receive denosumab.
Number of Participants Receiving GCTB Interventions Surgery for GCTB	1 Count of Participants	3 Count of Participants
Number of Participants Receiving GCTB Interventions Chemotherapy or Other Therapeutic Agents	0 Count of Participants	2 Count of Participants
Number of Participants Receiving GCTB Interventions Embolization	0 Count of Participants	0 Count of Participants
Number of Participants Receiving GCTB Interventions Interferon	0 Count of Participants	0 Count of Participants
Number of Participants Receiving GCTB Interventions Radiotherapy	0 Count of Participants	0 Count of Participants

Adverse Events

Exposed to IP

Serious events: 8 serious events

Other events: 37 other events

Deaths: 0 deaths

Not Exposed to IP

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Exposed to IP n=51 participants at risk Subjects treated with study IP	Not Exposed to IP n=34 participants at risk Subjects not treated with study IP
Blood and lymphatic system disorders Anaemia	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Gastrointestinal disorders Anal fistula	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Gastrointestinal disorders Gastrointestinal obstruction	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations Medical device site infection	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations Sepsis	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations Viral pericarditis	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Injury, poisoning and procedural complications Femur fracture	3.9% 2/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Injury, poisoning and procedural complications Patella fracture	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Myositis	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Osteosarcoma	2.0% 1/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

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

Measure	Exposed to IP n=51 participants at risk Subjects treated with study IP	Not Exposed to IP n=34 participants at risk Subjects not treated with study IP
Blood and lymphatic system disorders Anaemia	7.8% 4/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Gastrointestinal disorders Toothache	15.7% 8/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
General disorders Pyrexia	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations COVID-19	13.7% 7/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations Gingivitis	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Infections and infestations Sinusitis	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Injury, poisoning and procedural complications Foot fracture	7.8% 4/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Metabolism and nutrition disorders Hypocalcaemia	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Arthralgia	15.7% 8/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Back pain	13.7% 7/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Myalgia	7.8% 4/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	11.8% 6/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Musculoskeletal and connective tissue disorders Pain in extremity	15.7% 8/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Nervous system disorders Headache	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Respiratory, thoracic and mediastinal disorders Cough	9.8% 5/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 3/51 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.	0.00% 0/34 • Up to Approximately 5 years FAS included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.