Trial record 14 of 21 for:    "Osteogenesis Imperfecta"

Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01417091
First received: August 4, 2011
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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.

Twelve to 15 patients will be enrolled.


Condition Intervention Phase
Osteogenesis Imperfecta
Drug: BPS804
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events) [ Time Frame: Day 1 through 141 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Determination of the maximal concentration after the second dose [ Time Frame: Day 15 (prior to administration and 1x after administration) and Day 16 ] [ Designated as safety issue: No ]
    The maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Determination of the concentration of total sclerostin in serum [ Time Frame: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141 ] [ Designated as safety issue: No ]
    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

  • Immunogenicity evaluation in serum [ Time Frame: Days 1, 29, 85, and 141 ] [ Designated as safety issue: No ]
    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.


Enrollment: 10
Study Start Date: June 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment group Drug: BPS804
No Intervention: Untreated reference group

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417091

Locations
United States, California
Novartis Investigative Site
Anaheim, California, United States, 92801
United States, Florida
Novartis Investigative Site
Miramar, Florida, United States, 33025
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Gent, Belgium, 9000
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3GIA6
Germany
Novartis Investigative Site
Wuerzburg, Germany, 97074
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01417091     History of Changes
Other Study ID Numbers: CBPS804A2201, 2011-001465-41
Study First Received: August 4, 2011
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Belgium HA: Federal Agency for Medicines and Health Products
Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
Brittle bone disease
inherited
connective tissue disorder
fracture

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Bone Diseases
Bone Diseases, Developmental
Collagen Diseases
Connective Tissue Diseases
Genetic Diseases, Inborn
Musculoskeletal Diseases
Osteochondrodysplasias

ClinicalTrials.gov processed this record on October 21, 2014