To describe the safety and tolerability of up to 5 years denosumab administration as measured by adverse event monitoring, immunogenicity, and safety laboratory parameters in subjects who previously received denosumab.
ID
Source
Brief title
Condition
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety monitoring, including adverse event incidence, serious adverse event
incidence, changes in safety laboratory analytes (serum chemistry, hematology)
and subject incidence of anti-denosumab antibody formation in subjects
previously treated with denosumab who receive up to 5 years of denosumab
administration
Secondary outcome
- BMD of the lumbar spine, total hip and in a subset of subjects distal radius
at month 12 and month 24
- Vertebral fractures at month 24 and non-vertebral fractures at month 12 and
month 24
- Bone Turnover Markers (Type 1 CTX, iPTH, RANKL, OPG, BALP, P1NP) in a subset
of subjects at Day 10, month 6, month 12 and month 24
- Serum calcium values at Day 10
- Bone histology in a subset of subjects previously treated with denosumab who
receive up to 5 years of denosumab administration
- Safety monitoring, including adverse event incidence, serious adverse event
incidence, changes in safety laboratory analytes (serum chemistry, hematology),
and subject incidence of anti denosumab antibody formation in subjects
previously treated with placebo who receive up to 2 years of denosumab
administration
Background summary
Protocol 20030216 is an ongoing double blind, placebo-controlled, Phase 3 study
to evaluate denosumab at a dose of 60 mg administered SC every 6 months, in the
treatment of post menopausal osteoporosis. All subjects who complete the
20030216 protocol, remain on investigational product, and meet the
inclusion/exclusion criteria will be invited to participate in the 20060289
study to receive open-label denosumab 60mg every 6 months for two years,
regardless of their prior randomization to placebo or denosumab.
Study objective
To describe the safety and tolerability of up to 5 years denosumab
administration as measured by adverse event monitoring, immunogenicity, and
safety laboratory parameters in subjects who previously received denosumab.
Study design
Subjects who have completed the 20030216 study will be eligible to participate
in this study, if they did not missed two or more investigational product doses
and did complete the month 36 visit. Subjects must be dosed within 28 days of
the 20030216 study month 36 visit.
Subjects will be dosed every 6 months (i.e. at Day 1, 6 months, 12 months and
18 months) and followed over a 24 month period.
Intervention
Subjects will receive a 60mg SC injection of denosumab every 6 months for 24
months (at Day 1, 6 months, 12 months and 18 months)
Study burden and risks
Load for the patients:
The following procedures will be performed per the schedule outlined in
Appendix A: physical exam, vital signs, DXA, lateral radiographs, hematology,
serum chemistry, serum calcium and albumin, and anti-denosumab antibody
levels. Adverse events, clinical fractures, and concomitant medications will
be recorded throughout study participation.
Risk:
In patients receiving denosumab, the most frequent adverse events occurring
very commonly ( >=10%) in clinical trials included upper respiratory tract
infection or inflammation (such as sore throat); nausea, headache, pain in
joints, back and extremities, urinary tract infection, constipation, bone pain,
weakness, fatigue, flu, high blood pressure, upset stomach, vomiting,
rheumatoid arthritis (in patients with rheumatoid arthritis only) and diarrhea.
A short term decrease in blood calcium levels below normal has been observed in
some subjects, and occasionally has been associated with symptoms.
Osteonecrosis of the jaw has been reported in patients treated with
bisphosphonates. The potential risk of osteonecrosis of the jaw in patients
receiving denosumab is unknown. The effect of denosumab on bone resorption
appears fully reversible and discontinuing the drug can lead to reversal of the
gains made in bone density. Development of antibodies to denosumab in patients
has been uncommon. To date, no clinical effects have been observed in patients
who have developed antibodies to denosumab.
Minervum 7061
4800DH Breda
NL
Minervum 7061
4800DH Breda
NL
Listed location countries
Age
Inclusion criteria
- Subjects must sign the informed consent before any study specific procedures are performed and agree to receive denosumab 60mg SC injection every 6 months.
- Subjects must not have discontinued investigational product during the 20030216 study and must have attended the 20030216 study month 36 visit
Exclusion criteria
- Permanently non-ambulatory subjects (use of an assistive device e.g. cane, walker etc is permitted)
- Missed two or more investigational product doses during the 20030216 study
- Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures
- Developed sensitivity to mammalian cell derived drug products during the 20030216 study
- Unable to tolerate calcium supplementation during the last 6 months of participation in the 20030216 study (between the month 30 and month 36 20030216 study visits)
- Receiving any investigational product other than denosumab
- Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone.
- For bone biopsy sub-study subjects only: known or suspected sensitivity or contraindication to tetracycline derivatives
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001041-17-NL |
| ClinicalTrials.gov | NCTnummernognietbekend |
| CCMO | NL18474.091.07 |