Giant Cell Tumor of Bone
Conditions
Brief summary
Study 20140114 will continue to follow participants with GCTB who were treated in Study 20062004 and remained on the study at the completion of Study 20062004 for an additional 5 years on long-term safety follow up.
Detailed description
Study 20140114 will continue to follow participants with GCTB who were treated in Study 20062004 and remained on the study at the completion of Study 20062004 for an additional 5 years on long-term safety follow up. Collection of long-term safety information will include adverse events of interest and all treatment-emergent adverse events and serious adverse events
Interventions
DRUGDenosumab
120 mg administered subcutaneously (SC) every 4 weeks (Q4W).
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Participant was previously enrolled in Study 20062004. * Participant or participant's legally acceptable representative has provided informed consent/assent prior to initiation of any study-specific activities/procedures.
Exclusion criteria
* Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge. * Females of childbearing potential on denosumab and not willing to continue to use 1 highly effective method of contraception during treatment and for 5 months after the end of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Up to approximately 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | Up to approximately 5 years | 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). |
| Number of Participants With Disease Progression or Recurrence of GCTB | Up to approximately 5 years | 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. |
| Number of Participants Receiving GCTB Interventions | Up to approximately 5 years | GCTB interventions include: surgery, chemotherapy, embolization, interferon, and radiotherapy. |
Countries
Australia, France, Italy, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
Participants in the study were enrolled upon completing study 20062004.
Participants by arm
| Arm | Count |
|---|---|
| Exposed to 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 Q4W SC) and schedule at the investigator's discretion. | 51 |
| 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. | 34 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Decision by Sponsor | 6 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 4 |
Baseline characteristics
| Characteristic | Exposed to IP | Not Exposed to IP | Total |
|---|---|---|---|
| Age, Continuous | 42.4 Years STANDARD_DEVIATION 12.8 | 46.7 Years STANDARD_DEVIATION 15.1 | 44.1 Years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 24 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black (or African American) | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 35 Participants | 31 Participants | 66 Participants |
| Sex: Female, Male Female | 32 Participants | 23 Participants | 55 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 2 / 34 |
| other Total, other adverse events | 37 / 51 | 0 / 34 |
| serious Total, serious adverse events | 8 / 51 | 0 / 34 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Adjudicated positive ONJ | 3 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Malignancy, including malignancy in GCTB | 6 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Adjudicated positive AFF | 2 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Hypocalcemia | 3 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Hypocalcemia after treatment end | 0 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Pregnancy and lactation | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Hypocalcemia after treatment end | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Adjudicated positive ONJ | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Hypocalcemia | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Malignancy, including malignancy in GCTB | 1 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Pregnancy and lactation | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI) | Adjudicated positive AFF | 0 Count of Participants |
Secondary
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | All TEAEs | 47 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 8 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | Fatal TEAEs | 0 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | TEAEs leading to IP discontinuation | 9 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3, 4, or 5 | 16 Count of Participants |
| Exposed to IP | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE) | All TEAEs related to IP | 14 Count of Participants |
Secondary
Number of Participants Receiving GCTB Interventions
GCTB interventions include: surgery, chemotherapy, embolization, interferon, and radiotherapy.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exposed to IP | Number of Participants Receiving GCTB Interventions | Chemotherapy or Other Therapeutic Agents | 0 Count of Participants |
| Exposed to IP | Number of Participants Receiving GCTB Interventions | Interferon | 0 Count of Participants |
| Exposed to IP | Number of Participants Receiving GCTB Interventions | Surgery for GCTB | 1 Count of Participants |
| Exposed to IP | Number of Participants Receiving GCTB Interventions | Radiotherapy | 0 Count of Participants |
| Exposed to IP | Number of Participants Receiving GCTB Interventions | Embolization | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Receiving GCTB Interventions | Radiotherapy | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Receiving GCTB Interventions | Surgery for GCTB | 3 Count of Participants |
| Not Exposed to IP | Number of Participants Receiving GCTB Interventions | Chemotherapy or Other Therapeutic Agents | 2 Count of Participants |
| Not Exposed to IP | Number of Participants Receiving GCTB Interventions | Embolization | 0 Count of Participants |
| Not Exposed to IP | Number of Participants Receiving GCTB Interventions | Interferon | 0 Count of Participants |
Secondary
Number of Participants With Disease Progression or Recurrence of GCTB
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exposed to IP | Number of Participants With Disease Progression or Recurrence of GCTB | 5 Count of Participants |
| Not Exposed to IP | Number of Participants With Disease Progression or Recurrence of GCTB | 3 Count of Participants |