Clinical Trial: Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Multicenter Study to Evaluate Safety of Fresolimumab in Adults With Moderate-to-severe Osteogenesis Imperfecta

Brief Summary:

Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. OI can range from very severe to very mild. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.

Transforming growth factor beta (TGF-β) is a protein important in bone formation. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength. The purpose of this study is to determine if fresolimumab is safe in the treatment of OI.


Detailed Summary:

Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. OI can range from very severe to very mild. Individuals with the most severe type of OI may die at birth. People with severe OI who survive may have bowed arms and legs, very short stature and be unable to walk. People with the mildest form of OI may only break bones occasionally and have normal height and lifespan. Breaks can occur in any bone, but are most common in the arms and legs. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.

TGF-β is a protein important in bone formation. Studies have shown that increased TGF-β activity leads to lower bone mass and strength and increased fractures. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength.


Sponsor: Baylor College of Medicine

Current Primary Outcome: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 6 months for single dose study and 12 months for repeat dose study ]

Safety of single and repeat doses of fresolimumab will be assessed in adult patients with moderate to severe osteogenesis imperfecta


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Percentage change in type 1 procollagen, N-terminal or P1NP, Osteocalcin or Ocn, and C-terminal telopeptide or CTX [ Time Frame: 6 months in single dose study and 12 months in repeat dose study ]
    Markers of bone turnover in blood will be assessed
  • Percent change in the areal BMD at the lumbar spine and hip [ Time Frame: 6 months in single dose study and 12 months in repeat dose study ]
    Areal bone mineral density (aBMD) at the hip or the lumbar spine as measured by DXA Scan
  • Difference in score of numeric rating scale for pain [ Time Frame: 12 months ]
    The difference between baseline values and at month 12 will be assessed in the repeat dose study only
  • Change in ml in FEV1 [ Time Frame: 12 months ]
    The change in absolute volumes of FEV1 will be assessed between baseline and 12 months in the repeat dose study only
  • Change in ml in FVC [ Time Frame: 12 months ]
    The change in absolute volumes of FVC will be assessed between baseline and 12 months in the repeat dose study only
  • Percent change in volumetric bone mineral density at the radius [ Time Frame: 12 months ]
    pQCT of forearm will be performed to assess the change in volumetric bone mineral density between baseline and 12 months in the repeat dose study only.
  • Number of meters walked in 6 minutes [ Time Frame: 12 months ]
    Standard 6 minute walk test will be performed to assess the difference between baseline and 12 months in the repeat dose study only


Original Secondary Outcome:

  • Percentage change in type 1 procollagen, N-terminal or P1NP, Osteocalcin or Ocn, and C-terminal telopeptide or CTX [ Time Frame: 6 months in single dose study and 12 months in repeat dose study ]
    Markers of bone turnover in blood will be assessed
  • Percent change in the areal BMD at the lumbar spine and hip [ Time Frame: 6 months in single dose study and 12 months in repeat dose study ]
    Areal bone mineral density (aBMD) at the hip or the lumbar spine as measured by DXA Scan
  • Difference in score of numeric rating scale for pain [ Time Frame: 12 months ]
    The difference between baseline values and at month 12 will be assessed in the repeat dose study only
  • Change in ml in FEV1 and FVC [ Time Frame: 12 months ]
    The change in absolute volumes of FEV1 and FVC will be assessed between baseline and 12 months in the repeat dose study only
  • Percent change in volumetric bone mineral density at the radius [ Time Frame: 12 months ]
    pQCT of forearm will be performed to assess the change in volumetric bone mineral density between baseline and 12 months in the repeat dose study only.
  • Number of meters walked in 6 minutes [ Time Frame: 12 months ]
    Standard 6 minute walk test will be performed to assess the difference between baseline and 12 months in the repeat dose study only


Information By: Baylor College of Medicine

Dates:
Date Received: October 13, 2016
Date Started: April 2017
Date Completion: April 2019
Last Updated: February 23, 2017
Last Verified: February 2017