HypophosphatasiaPhase 2NCT01406977
Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)
A Phase 2 study testing BPS804 in people with Hypophosphatasia, run by Ultragenyx Pharmaceutical Inc at 1 site in Germany.
Trial summary
The purpose of the study is to determine tolerability, PK/PD and preliminary efficacy of BPS804 in adult patients with HPP treated with multiple escalating doses of BPS804. This study will allow a comparison of several doses of the study drug within the first two weeks after administration and after a longer… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- BPS804
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2011to Sep 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients 18 to 60 years of age in good health (other than pre-established clinical diagnosis of HPP) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- Previously established clinical diagnosis of HPP with confirmed ALPL mutation by genetic test and as manifested by:
- Serum alkaline phosphatase levels below the age-adjusted normal range and
- Radiologic evidence of osteopenia or osteomalacia or
- History of plasma PLP at least twice the upper limit of normal range or
- History of rickets, or history of premature loss of deciduous teeth, or bone deformity consistent with osteomalacia or past rickets, or past non-traumatic fracture, pseudofracture, or non-healing fracture.
- 25-(OH) vitamin D3 serum level of ≥20 ng/mL.
- Normocalcemia with serum calcium ≥8.5 mg/dL and ≤10.2 mg/dL and normal phosphate levels (2.4 - 4.1 mg/dL) (or according to local laboratory ranges).
Who cannot join
- A history of clinically significant ECG abnormalities.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin and for skeletal malignancies see below), within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- History of skeletal malignancies or bone metastases at any time.
- History of external beam radiation to the skeleton.
- Open epiphyses as judged by the Investigator based on previous clinical assessments.
- Patients with suspected neural foraminal stenosis (e.g., at cervical, spinal, or lumbar site) as judged by the Investigator which could be caused by disc herniation and are described as sciatic pain, tingling, burning sensation with numbness and/or weakness.
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- History of or concomitant diseases such as hypo-/hyperparathyroidism, hypo-/hyperthyroidism, Pagets disease, previous neck surgery involving partial or complete thyroidectomy and abnormal thyroid function or thyroid disease or other endocrine disorders or conditions.
- Treatment with any anti-resorptive medication (e.g., oral and/or injectable), bisphosphonates and/or teriparatide (e.g., ForteoTM) within the last 6 months.
- Exposure to blood products or monoclonal antibodies within previous 12 months.
- Any deformation of the spine (e.g., severe scoliosis, ankylosing spondylitis) or the hip which would preclude proper acquisition of lumbar spine or hip BMD by DXA.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Intra-patient Dose-escalation Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP).
The purpose of the study is to determine tolerability, PK/PD and preliminary efficacy of BPS804 in adult patients with HPP treated with multiple escalating doses of BPS804.
This study will allow a comparison of several doses of the study drug within the first two weeks after administration and after a longer assessment period for the highest dose level to enable selection of dose ranges to be tested in subsequent studies in the HPP indication.
Read the detailed description
This study was conducted and previously posted by Novartis. The record was transferred to Ultragenyx in February 2021.
- Conditions
- Hypophosphatasia
- Being tested
- BPS804
- Keywords
- Hypophosphatasia, HPP, Rathbun's disease
- Medical subject headings
- Hypophosphatasia
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 |
|---|---|---|
| BPS804 dose escalation | Experimental | BPS804 IV Setrusumab given in escalating doses from 5mg/Kg to 20mg/Kg Receives: Drug: BPS804 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number (percent) of patients experiencing adverse events or serious adverse events
Measured: 141 days following initial investigational product administration
Change from baseline in primary serological bone biomarkers
Measured: 141 days following initial investigational product administration
Secondary outcomes (5)
Characterization of the pharmacokinetic profile of BPS804: area under the plasma concentration-time curve (AUC)
Measured: 1, 29 and 141 days following initial investigational product administration
Characterization of the pharmacokinetic profile of BPS804: observed maximum plasma concentration following drug administration (Cmax)
Measured: 1, 15 and 29 days following initial investigational product administration
Characterization of the pharmacokinetic profile of BPS804: time to reach the maximum concentration (Tmax)
Measured: 1, 15 and 29 days following initial investigational product administration
Change from baseline in secondary biomarkers
Measured: 141 days following initial investigational product administration
The number (percent) of patients developing anti-BPS804 antibodies
Measured: 141 days following initial investigational product administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2011 (estimated)
- Study startJul 2011
- Primary completionSep 2012
- Study completionSep 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 HypophosphatasiaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mereo BioPharma, Novartis
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01406977
- Sponsor's protocol ID
- CBPS804A2202
- Other IDs
- 2010-024013-31
- Status last verified
- Sep 2022
- First submitted
- 29 Jul 2011
- Last updated
- 16 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Seefried L, Baumann J, Hemsley S, Hofmann C, Kunstmann E, Kiese B, Huang Y, Chivers S, Valentin MA, Borah B, Roubenoff R, Junker U, Jakob F. Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia. J Clin Invest. 2017 Jun 1;127(6):2148-2158. doi: 10.1172/JCI83731. Epub 2017 Apr 24.
PubMed 28436937
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Intra-patient Dose-escalation Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP).
- ClinicalTrials.gov ID
- NCT01406977
- Acronym / sponsor ID
- CBPS804A2202
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP, Rathbun's disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Collaborators
- Mereo BioPharma, Novartis
- Study start
- Jul 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 1 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.
The purpose of the study is to determine tolerability, PK/PD and preliminary efficacy of BPS804 in adult patients with HPP treated with multiple escalating doses of BPS804.
This study will allow a comparison of several doses of the study drug within the first two weeks after administration and after a longer assessment period for the highest dose level to enable selection of dose ranges to be tested in subsequent studies in the HPP indication.
Detailed description
This study was conducted and previously posted by Novartis. The record was transferred to Ultragenyx in February 2021.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BPS804 dose escalation | Experimental | Drug: BPS804BPS804 IV Setrusumab given in escalating doses from 5mg/Kg to 20mg/Kg |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients 18 to 60 years of age in good health (other than pre-established clinical diagnosis of HPP) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- Previously established clinical diagnosis of HPP with confirmed ALPL mutation by genetic test and as manifested by:
- Serum alkaline phosphatase levels below the age-adjusted normal range and
- Radiologic evidence of osteopenia or osteomalacia or
- History of plasma PLP at least twice the upper limit of normal range or
Key exclusion criteria (11 listed)
- A history of clinically significant ECG abnormalities.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin and for skeletal malignancies see below), within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- History of skeletal malignancies or bone metastases at any time.
- History of external beam radiation to the skeleton.
- Open epiphyses as judged by the Investigator based on previous clinical assessments.
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 | BPS804 dose escalation |
Primary outcome
The number (percent) of patients experiencing adverse events or serious adverse events
Time frame: 141 days following initial investigational product administration
Change from baseline in primary serological bone biomarkers
Time frame: 141 days following initial investigational product administration
5 secondary outcomes
Characterization of the pharmacokinetic profile of BPS804: area under the plasma concentration-time curve (AUC)
Time frame: 1, 29 and 141 days following initial investigational product administration
Characterization of the pharmacokinetic profile of BPS804: observed maximum plasma concentration following drug administration (Cmax)
Time frame: 1, 15 and 29 days following initial investigational product administration
Characterization of the pharmacokinetic profile of BPS804: time to reach the maximum concentration (Tmax)
Time frame: 1, 15 and 29 days following initial investigational product administration
Change from baseline in secondary biomarkers
Time frame: 141 days following initial investigational product administration
The number (percent) of patients developing anti-BPS804 antibodies
Time frame: 141 days following initial investigational product administration
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 16 Sep 2022.
- Derived from this study: PubMed 28436937Seefried L, Baumann J, Hemsley S, Hofmann C, Kunstmann E, Kiese B, Huang Y, Chivers S, Valentin MA, Borah B, Roubenoff R, Junker U, Jakob F. Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia. J Clin Invest. 2017 Jun 1;127(6):2148-2158. doi: 10.1172/JCI83731. Epub 2017 Apr 24.
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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
1 site in 1 country: 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 Hypophosphatasia, run by Ultragenyx Pharmaceutical Inc at 1 site in Germany.
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 8 inclusion and 11 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 16 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
The number (percent) of patients experiencing adverse events or serious adverse events (time frame: 141 days following initial investigational product administration). The study lists 2 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 NCT01406977, 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 16 Sep 2022.