Osteogenesis ImperfectaPhase 2NCT01417091
Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
A Phase 2 study testing BPS804 in people with Osteogenesis Imperfecta, run by Ultragenyx Pharmaceutical Inc at 6 sites in 4 countries.
Trial summary
This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 in adults with osteogenesis imperfecta (OI). Pharmacodynamic effect will be determined by serological biomarkers and radiologic assessments. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Osteogenesis Imperfecta
- What is being tested?
- BPS804
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 6 sitesin 4 countries
- Study dates
- Jun 2011to Dec 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Osteogenesis imperfecta
- Two or more previous fractures
- Bone mineral density Z-score of ≤ -1.0 and > -4.0
Who cannot join
- Open epiphyses
- Fracture within last 2 weeks
- Treatment with bisphosphonates/teriparatide (last 6 months)
- Surgery within last year
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States2 sites
Novartis Investigative Site
Anaheim, California, 92801
Novartis Investigative Site
Miramar, Florida, 33025
Belgium2 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Ghent, 9000
About this study
Official title: A Randomized, Open Label Intra-patient Dose Escalation Study With an Untreated Reference Group to Evaluate Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Infusions of BPS804 in Adults With Moderate Osteogenesis Imperfecta
This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 in adults with osteogenesis imperfecta (OI).
Pharmacodynamic effect will be determined by serological biomarkers and radiologic assessments. In addition, tolerability and pharmacokinetics (PK) will be evaluated.
Read the detailed description
This study was previously posted by Mereo BioPharma and was transferred to Ultragenyx in February 2021.
- Conditions
- Osteogenesis Imperfecta
- Being tested
- BPS804
- Keywords
- Brittle bone disease, inherited, connective tissue disorder, fracture
- Medical subject headings
- Osteogenesis Imperfecta, Connective Tissue Diseases, Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPS804Drug
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Not described Receives: Drug: BPS804 |
| Untreated reference group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
The assessment of safety will be based on primarily on the frequency of adverse events, laboratory abnormalities, and serious adverse events suspected by the investigators to be related to study treatments. The AE collection period extends from the time of first study drug administration drug until study completion. The intensity of each AE will be characterized and classified into 1 of the 3 generic categories (mild, moderate, or severe). The number and percentage of patients with adverse events will be tabulated by treatment group, body system and preferred term. The periods for adverse event tabulation will be from dose administration up to next dose administration if a further dose is given, and from dose administration to EOS for the last dose administration of a patient.
Measured: Day 1 through 141
Determination of pharmacodynamic effect by means of biomarkers
Biomarker data from serum bone formation biomarkers: procollagen type I N-terminal propeptide, procollagen type I C-terminal propeptide, osteocalcin, and bone-specific alkaline phosphatase, and from serum bone resporption mbiomarkers: C-telopeptides of type I collagen cross-links, and N-telopeptides of type I collagen cross-links will be reported as concentration results, measured using a specific assay with a working range defined by the Lower limit of quantification and Upper limit of quantification. It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 43.
Measured: Day 1 and Day 43
Change in Z-score from baseline to Day 141
Bone mineral density will be assessed by dual-energy X-ray absorptiometry of the lumbar spine. Analysis will include four vertebral levels from L1 to L4. Individual vertebral levels may be excluded due to artifact. Bone mineral density Z-scores will be used as these are a comparison of a patient's BMD to that of a patient of the same age, sex, and ethnicity. The comparison of change from baseline with the matching change in the reference group will be done by 2-sample t-tests (1-sided). It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 141.
Measured: Day 1 and Day 141
Secondary outcomes (14)
Determination of the serum concentration-time profiles of BPS804
Individual and overlaying individual serum concentration-time profiles of BPS804 will be constructed from the serial sampling on Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141. In addition arithmetic and geometric mean serum concentration-time profiles of BPS804 will be constructed from the above data points.
Measured: Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose will be derived using using non-compartmental methods from data collected on Day 1 (4x) and Days 2, and 8.
Measured: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the maximal concentration after the first dose
The maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
Measured: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the time of maximal concentration after the first dose
The time of maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
Measured: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the maximal concentration after the second dose
The maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
Measured: Day 15 (prior to administration and 1x after administration) and Day 16
Determination of the time of maximal concentration after the second dose
The time of maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
Measured: Day 15 (prior to administration and 1x after administration) and Day 16
Determination of the area under the serum concentration-time curve from time zero to infinity after the third dose
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose
The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose
The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the maximal serum concentration after the third dose
The maximal serum concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the time of maximal concentration after the third dose
The time of maximal concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the terminal elimination half-life after the third dose
The terminal elimination half-life after the third dose will be derived from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141 using a compound-specific modeling approach.
Measured: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the concentration of total sclerostin in serum
The function of sclerostin is described as an endogenous negative regulator of bone formation. Total serum sclerostin will be measured from samples collected at screening and on days 1, 8, 15, 29, 36, 43, 57, 85, 113, and 141
Measured: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
Immunogenicity evaluation in serum
Immunogenicity will only be assessed in patients randomized to the treatment group. Anti-BPS804 antibodies will be measured in human serum on Days 1, 29, 85, and 141 An immunogenicity positive patient at end of study will be followed up until anti-BPS804 antibody levels are back to levels measured on Day 1.
Measured: Days 1, 29, 85, and 141
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2011 (estimated)
- Study startJun 2011
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteogenesis ImperfectaStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01417091
- Sponsor's protocol ID
- CBPS804A2201
- Other IDs
- 2011-001465-41
- Status last verified
- May 2021
- First submitted
- 4 Aug 2011
- Last updated
- 11 May 2021
- Results posted
- No
Publications
Glorieux FH. Osteogenesis imperfecta. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):85-100. doi: 10.1016/j.berh.2007.12.012.
PubMed 18328983
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label Intra-patient Dose Escalation Study With an Untreated Reference Group to Evaluate Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Infusions of BPS804 in Adults With Moderate Osteogenesis Imperfecta
- ClinicalTrials.gov ID
- NCT01417091
- Acronym / sponsor ID
- CBPS804A2201
- Conditions
- Osteogenesis Imperfecta
- Keywords
- Brittle bone disease, inherited, connective tissue disorder, fracture
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 16 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 in adults with osteogenesis imperfecta (OI).
Pharmacodynamic effect will be determined by serological biomarkers and radiologic assessments. In addition, tolerability and pharmacokinetics (PK) will be evaluated.
Detailed description
This study was previously posted by Mereo BioPharma and was transferred to Ultragenyx in February 2021.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: BPS804 |
| Untreated reference group | No intervention | – |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Osteogenesis imperfecta
- Two or more previous fractures
- Bone mineral density Z-score of ≤ -1.0 and > -4.0
Key exclusion criteria (5 listed)
- Open epiphyses
- Fracture within last 2 weeks
- Treatment with bisphosphonates/teriparatide (last 6 months)
- Surgery within last year
- Other protocol-defined inclusion/exclusion criteria may apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BPS804 | Drug | Treatment group |
Primary outcome
Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Time frame: Day 1 through 141
The assessment of safety will be based on primarily on the frequency of adverse events, laboratory abnormalities, and serious adverse events suspected by the investigators to be related to study treatments. The AE collection period extends from the time of first study drug administration drug until study completion. The intensity of each AE will be characterized and classified into 1 of the 3 generic categories (mild, moderate, or severe). The number and percentage of patients with adverse events will be tabulated by treatment group, body system and preferred term. The periods for adverse event tabulation will be from dose administration up to next dose administration if a further dose is given, and from dose administration to EOS for the last dose administration of a patient.
Determination of pharmacodynamic effect by means of biomarkers
Time frame: Day 1 and Day 43
Biomarker data from serum bone formation biomarkers: procollagen type I N-terminal propeptide, procollagen type I C-terminal propeptide, osteocalcin, and bone-specific alkaline phosphatase, and from serum bone resporption mbiomarkers: C-telopeptides of type I collagen cross-links, and N-telopeptides of type I collagen cross-links will be reported as concentration results, measured using a specific assay with a working range defined by the Lower limit of quantification and Upper limit of quantification. It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 43.
Change in Z-score from baseline to Day 141
Time frame: Day 1 and Day 141
Bone mineral density will be assessed by dual-energy X-ray absorptiometry of the lumbar spine. Analysis will include four vertebral levels from L1 to L4. Individual vertebral levels may be excluded due to artifact. Bone mineral density Z-scores will be used as these are a comparison of a patient's BMD to that of a patient of the same age, sex, and ethnicity. The comparison of change from baseline with the matching change in the reference group will be done by 2-sample t-tests (1-sided). It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 141.
14 secondary outcomes
Determination of the serum concentration-time profiles of BPS804
Time frame: Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose
Time frame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the maximal concentration after the first dose
Time frame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the time of maximal concentration after the first dose
Time frame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
Determination of the maximal concentration after the second dose
Time frame: Day 15 (prior to administration and 1x after administration) and Day 16
Determination of the time of maximal concentration after the second dose
Time frame: Day 15 (prior to administration and 1x after administration) and Day 16
Determination of the area under the serum concentration-time curve from time zero to infinity after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the maximal serum concentration after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the time of maximal concentration after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the terminal elimination half-life after the third dose
Time frame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
Determination of the concentration of total sclerostin in serum
Time frame: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
Immunogenicity evaluation in serum
Time frame: Days 1, 29, 85, and 141
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Background: PubMed 18328983Glorieux FH. Osteogenesis imperfecta. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):85-100. doi: 10.1016/j.berh.2007.12.012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BPS804 in people with Osteogenesis Imperfecta, run by Ultragenyx Pharmaceutical Inc at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Belgium, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events) (time frame: Day 1 through 141). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01417091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.