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Trial record 4 of 6 for:    BPS804

Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01406977
Recruitment Status : Completed
First Posted : August 1, 2011
Last Update Posted : March 20, 2013
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE July 29, 2011
First Posted Date  ICMJE August 1, 2011
Last Update Posted Date March 20, 2013
Study Start Date  ICMJE July 2011
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2011)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01406977 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2011)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)
Official Title  ICMJE 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).
Brief 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 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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypophosphatasia
Intervention  ICMJE Drug: BPS804
Study Arms  ICMJE Experimental: BPS804 dose escalation
Intervention: Drug: BPS804
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 29, 2011)
9
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 decidious 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).

Exclusion Criteria:

  • 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.
  • 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01406977
Other Study ID Numbers  ICMJE CBPS804A2202
2010-024013-31
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP