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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01406977
First received: July 29, 2011
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Hypophosphatasia
Drug: BPS804
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The number (percent) of patients experiencing adverse events or serious adverse events [ Time Frame: 141 days following initial investigational product administration ] [ Designated as safety issue: Yes ]
  • Change from baseline in primary serological bone biomarkers [ Time Frame: 141 days following initial investigational product administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in secondary biomarkers [ Time Frame: 141 days following initial investigational product administration ] [ Designated as safety issue: No ]
  • The number (percent) of patients developing anti-BPS804 antibodies [ Time Frame: 141 days following initial investigational product administration ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: July 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BPS804 dose escalation Drug: BPS804

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT01406977

Locations
Germany
Novartis Investigative Site
Wuerzburg, Germany, 97074
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01406977     History of Changes
Other Study ID Numbers: CBPS804A2202, 2010-024013-31
Study First Received: July 29, 2011
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
Hypophosphatasia
HPP
Rathbun's disease

Additional relevant MeSH terms:
Hypophosphatasia
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on July 28, 2014