A Study to Evaluate the Safety and Effectiveness of Bimagrumab on Improvement in Total Lean Body Mass and Physical Performance Following Surgical Treatment of Hip Fracture.

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 15-007295
    NCT ID: NCT02152761
    Sponsor Protocol Number: CBYM338D2201

About this study

The purpose of this study is to identify an effective dose of bimagrumab that can increase lean muscle mass and improve physical function, then continue to assess the safety and effectiveness of bimagrumab in patients with muscle wasting after hip fracture surgery.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria

  • Patients eligible for inclusion in this study have to fulfill all of the following criteria
    • Written informed consent must be obtained before any assessment is performed
    • Males and post-menopausal females ≥ 60 years
    • Patient must have had surgical fixation or arthroplasty of the hip fracture( AO Classification 31 A-C) as confirmed by radiography
    • Patient must be mentally competent, to have scored at least ≥ 21 on the Folstein Mini Mental Status Examination (MMSE)
    • Patient must be able to complete a 4 meter gait speed test
    • Patients must weigh at least 35 kg and must have a body mass index (BMI) within the range of 15– 35 kg/m2 at screening
    • Patient must have complete surgical wound healing

 

Exclusion Criteria

  • Patients fulfilling any of the following criteria are not eligible for inclusion in this study
  • No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients
  • Central laboratory assessments or ECG interpretations which fall outside of the protocol specified range at screening can be repeated once at an unscheduled visit during the screening period to confirm patient eligibility prior to randomization
    • History of any other lower limb fracture in the past 6 months or any other major surgery to the lower limb in the past 3 months prior to randomization with persistent negative impact on lower extremity function
    • Presence of sub-trochanteric fractures (AO Classification 32 A-C)
    • Major mobility limitation (i.e. not able to walk 100 meters without stopping and without help; unilateral help being fine) in the past 3 months prior to the hip fracture due to
      • severe dyspnea
      • presence of permanent or progressive neurologic deficit (muscle weakness, spasticity, rigor or balance impairment)
      • disabling joint or muscle pain in the hip or knee
      • intermittent claudication 
      • major visual impairment
    • Active gastrointestinal diseases/conditions known to cause malabsorption or increased enteric loss of protein, such as
      • inflammatory bowel disease (unless in complete remission)
      • celiac disease (unless on gluten-free diet)
      • short bowel syndrome
      • pancreatic insufficiency
    • Severe renal insufficiency defined by either requiring dialysis or having an estimated glomerular filtration rate (GFR) < 30 mL/min
    • Uncontrolled hypothyroidism requiring a change in the dose of hormone replacement therapy in the last 6 weeks prior to randomization
    • Uncontrolled hyperthyroidism
    • Underlying muscle diseases, including history of or currently active form of inflammatory myopathies (e.g., dermatomyositis, polymyositis, etc) or muscular dystrophies
    • Vitamin D deficiency (defined as 25-OH-vitamin D levels < 12.0 ng/mL or < 30.0 nmol/L) not treated with appropriate vitamin D supplements prior to randomization
    • Hypertension uncontrolled with medication (i.e. systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mmHg
    • Known heart failure classified as New York Heart Association Class III and IV
    • Ongoing unstable angina or history of myocardial infarction in the last 3 months prior to randomization
    • Current presence of severe aortic or mitral stenosis, or septal defects
    • Severe pulmonary hypertension uncontrolled with medication
    • Confirmed diagnosis of restrictive or hypertrophic (obstruction) cardiomyopathy
      • Patients with dilative cardiomyopathy are allowed to enter the trial unless it is associated with any of the conditions/events outlined in exclusion criteria
    • History of familial long QT syndrome or known family history of Torsades de Pointes
    • Prolonged QT syndrome or QTcF ≥ 450 msec (Fridericia Correction) for males and ≥ 460 msec for females at screening (central reading)
    • Any current supra-ventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 beats per minute [bpm]) as per ECG at rest despite medical or device therapy
    • Any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for 30 seconds) despite medical or device therapy
    • Any history of resuscitated cardiac arrest
    • The presence of an automatic internal cardioverter-defibrillator
    • Abnormal liver function tests such as SGOT (AST), SGPT (ALT), or serum bilirubin
      • except if accompanying Gilbert’s Disease as defined by any single transaminase > 3 x the upper limit of normal.
      • A single parameter elevated up to and including 3 x ULN should be re-checked as soon as possible, and in all cases, prior to randomization, to rule out any lab error
    • Serum bilirubin > 1.6 mg/dL (27μmol/L).
    • Presence of severe acute or chronic liver disease (e.g., cirrhosis)
    • Conditions with hepatotoxic potential (e.g. known gallbladder or bile duct disease, acute or chronic pancreatitis)
    • History of hypersensitivity to therapeutically administered antibodies
    • Lack of peripheral venous access
    • Active cancer (i.e. under current treatment) 
    • Cancer requiring treatment in the last 5 years excluding non-melanoma skin cancers or cancers with excellent prognosis (e.g. carcinoma in situ of the uterine cervix)
    • Type I diabetes mellitus 
    • Uncontrolled type II diabetes mellitus (e.g. pre-surgical levels per patient file HbA1C ≥ 8% or average blood glucose ≥ 9.0 mmol/l)
    • Significant coagulopathy, platelet count less than 75,000/mm3, or anemia (hemoglobin less than 8.0 g/dL)
    • Active systemic infection requiring treatment with IV anti-infectives within 4 weeks of randomization
    • Chronic active infection (e.g., HIV, hepatitis B or C, tuberculosis, etc)
      • Patients receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study
    • Patient has any other condition (e.g. alcohol abuse) or laboratory finding, or has any postoperative condition or complication which in the opinion of the investigator may affect recovery from surgery, interfere with participation in the study, might confound the results of the study, or pose additional risk in administering bimagrumab
    • Systemic use of vascular endothelial growth factor (VEGF) inhibitors within 6 months prior to randomization
    • Use of immunosuppressive therapy within 3 months of randomization
    • Use of any therapies known to affect muscle mass via modulation of androgen or growth hormone receptors or the synthesis of these hormones within 3 months prior to randomization 
    • Current use of high-dose selective beta2-adrenergic drug therapy
    • Ongoing corticosteroid use or history of systemic corticosteroid use for at least 3 months in the last year prior to randomization, at a daily dose greater than or equal to 10 milligram (mg) prednisone equivalent
    • Currently enrolled in a clinical trial involving an investigational drug or off label use of a drug
    • Discontinued within the last 30 days or 5 half-lives, or until pharmacodynamic effect is expected to return to baseline, whichever is longer,( or longer if required by local regulations) from a clinical trial involving an investigational drug or off label use of a drug 
    • Are concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Drake, M.D., Ph.D.

Open for enrollment

Contact information:

Lori Rhodes L.G.S.W., M.S.W.

(507)255-9130

Rhodes.Lori@mayo.edu