Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta

NCT01417091 | Completed Phase 2

• 2 other identifiers: CBPS804A22012011-001465-41
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 6

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.

Conditions

Osteogenesis Imperfecta

Keywords

Brittle bone disease; inherited; connective tissue disorder; fracture

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Day 1 and Day 141

Secondary Outcomes (14)

• Determination of the serum concentration-time profiles of BPS804

  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

  Day 1 (prior to administration and 3x after administration) and Days 2, and 8

• Determination of the maximal concentration after the first dose

  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

  Day 1 (prior to administration and 3x after administration) and Days 2, and 8

• Determination of the maximal concentration after the second dose

  Day 15 (prior to administration and 1x after administration) and Day 16

Study Arms (2)

Treatment group

EXPERIMENTAL

Drug: BPS804

Untreated reference group

NO INTERVENTION

Interventions

BPS804 DRUG

Treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Open epiphyses
• Fracture within last 2 weeks
• Treatment with bisphosphonates/teriparatide (last 6 months)
• Surgery within last year

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (6)

Novartis Investigative Site

Anaheim, California, 92801, United States

Location

Novartis Investigative Site

Miramar, Florida, 33025, United States

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H3GIA6, Canada

Location

Novartis Investigative Site

Würzburg, 97074, Germany

Location

Related Publications (1)

• Glorieux FH. Osteogenesis imperfecta. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):85-100. doi: 10.1016/j.berh.2007.12.012.

  PMID: 18328983 BACKGROUND

MeSH Terms

Conditions

Osteogenesis Imperfecta; Connective Tissue Diseases; Fractures, Bone

Interventions

setrusumab

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Skin and Connective Tissue Diseases; Wounds and Injuries

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2011
• First Posted: August 16, 2011
• Study Start: June 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 11, 2021

Record last verified: 2021-05

Locations

US (2); DE (1); CA (1); BE (2)