Clinical trial NCT01417091: Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteogenesis Imperfecta
Keywords: Brittle bone disease
inherited
connective tissue disorder
fracture
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2011-08-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* Osteogenesis imperfecta
* Two or more previous fractures
* Bone mineral density Z-score of ≤ -1.0 and \> -4.0

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
timeFrame: Day 1 through 141
measure: Determination of pharmacodynamic effect by means of biomarkers
timeFrame: Day 1 and Day 43
measure: Change in Z-score from baseline to Day 141
timeFrame: Day 1 and Day 141
Secondary outcomes:
measure: Determination of the serum concentration-time profiles of BPS804
timeFrame: 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
measure: 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
timeFrame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
measure: Determination of the maximal concentration after the first dose
timeFrame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
measure: Determination of the time of maximal concentration after the first dose
timeFrame: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
measure: Determination of the maximal concentration after the second dose
timeFrame: Day 15 (prior to administration and 1x after administration) and Day 16
measure: Determination of the time of maximal concentration after the second dose
timeFrame: Day 15 (prior to administration and 1x after administration) and Day 16
measure: Determination of the area under the serum concentration-time curve from time zero to infinity after the third dose
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: 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
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: 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
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: Determination of the maximal serum concentration after the third dose
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: Determination of the time of maximal concentration after the third dose
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: Determination of the terminal elimination half-life after the third dose
timeFrame: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
measure: Determination of the concentration of total sclerostin in serum
timeFrame: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
measure: Immunogenicity evaluation in serum
timeFrame: Days 1, 29, 85, and 141
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Miramar
country: United States
facility: Novartis Investigative Site
state: Florida
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Glorieux FH. Osteogenesis imperfecta. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):85-100. doi: 10.1016/j.berh.2007.12.012.