Dose Range Finding Study of Bimagrumab in Sarcopenia

A 28 Week, Randomized, Double-blind, Placebo-controlled, Two-part, Multi-center, Parallel Group Dose Range Finding Study to Assess the Effect of Monthly Doses of Bimagrumab 70, 210, and 700 mg on Skeletal Muscle Strength and Function in Older Adults With Sarcopenia (InvestiGAIT)

The purpose of this study was to determine the efficacy of repeat dosing with multiple dose levels of bimagrumab on patient physical function, skeletal muscle mass and strength in older adults with sarcopenia. In addition, this study generated data on the safety, tolerability, and pharmacokinetics of bimagrumab in older adults with sarcopenia.

Study Overview

• Status: Completed
• Conditions: Sarcopenia
• Intervention / Treatment: Drug: bimagrumab; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Victoria
    • St Albans, Victoria, Australia, 3021
      • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 62500
    • Novartis Investigative Site
  • Opava, Czechia, 74601
    • Novartis Investigative Site
  • Praha 2, Czechia, 12000
    • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Novartis Investigative Site
  • Copenhagen NV, Denmark, 2400
    • Novartis Investigative Site
• France
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
  • Toulouse, France, 31052
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97074
    • Novartis Investigative Site
• Japan
  • Aichi
    • Obu-city, Aichi, Japan, 474-8511
      • Novartis Investigative Site
    • Toyohashi-city, Aichi, Japan, 440-8510
      • Novartis Investigative Site
  • Gifu
    • Mizunami-city, Gifu, Japan, 509 6134
      • Novartis Investigative Site
  • Nara
    • Nara-city, Nara, Japan, 630-8581
      • Novartis Investigative Site
  • Osaka
    • Kawachinagano-city, Osaka, Japan, 586-8521
      • Novartis Investigative Site
  • Saitama
    • Kitaadachigun Inamachi, Saitama, Japan, 362-0806
      • Novartis Investigative Site
    • Kitamoto-city, Saitama, Japan, 364-8501
      • Novartis Investigative Site
  • Tokushima
    • Yoshinogawa-city, Tokushima, Japan, 776-8585
      • Novartis Investigative Site
  • Tokyo
    • Itabashi ku, Tokyo, Japan, 173 0015
      • Novartis Investigative Site
    • Kiyose-city, Tokyo, Japan, 204-0021
      • Novartis Investigative Site
    • Koto-ku, Tokyo, Japan, 136-0075
      • Novartis Investigative Site
    • Musashimurayama-city, Tokyo, Japan, 208-0011
      • Novartis Investigative Site
• Korea, Republic of
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
    • Suwon si, Gyeonggi Do, Korea, Republic of, 16499
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 02447
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 101990
    • Novartis Investigative Site
  • Moscow, Russian Federation, 117997
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 190068
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08024
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Castilla La Mancha
    • Albacete, Castilla La Mancha, Spain, 02006
      • Novartis Investigative Site
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Novartis Investigative Site
• Switzerland
  • Genève 14, Switzerland, 1211
    • Novartis Investigative Site
  • CH
    • Basel, CH, Switzerland, 4002
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Novartis Investigative Site
  • California
    • Cypress, California, United States, 90630
      • Novartis Investigative Site
    • La Jolla, California, United States, 92093-9405
      • Novartis Investigative Site
  • Connecticut
    • Farmington, Connecticut, United States, 06030-5215
      • Novartis Investigative Site
  • Florida
    • Gainesville, Florida, United States, 32611
      • Novartis Investigative Site
    • Miami, Florida, United States, 33143
      • Novartis Investigative Site
    • Miami Lakes, Florida, United States, 33014
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32804
      • Novartis Investigative Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Novartis Investigative Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
  • Texas
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 66 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Low muscle mass as confirmed by DXA;
• Low gait speed <0.8 m/s
• SPPB score less than or equal to 9;
• Weigh at least 35 kg;
• Adequate dietary intake;

Exclusion Criteria:

• A lower limb fracture in the past 6 months or any impairment or disease severely affecting gait (e.g. stroke with hemiparesis, myasthenia gravis, Parkinson's disease, peripheral polyneuropathy, intermittent claudication in advanced peripheral vascular disease, spinal stenosis, or severe osteoarthritis of the knee or hip with ineffective pain management);
• Requires regular assistance from another person for general activities of daily living (e.g. bathing, dressing, toileting).
• Intraocular surgery and laser procedures for refractive correction within 6 months prior to screening;
• Any underlying muscle disease including active myopathy or muscular dytrophy;
• Confirmed diagnosis of heart failure classified as New York Heart Association Class III or IV (e.g. dilated cardiomyopathy);
• Type I diabetes or uncontrolled Type 2 diabetes;
• Chronic kidney disease [estimated glomerular filtration rate (GFR) < 30 mL/min];
• History of confirmed chronic obstructive pulmonary disease with a severity grade > 2 on the Medical Research Council Dyspnea Scale;
• Confirmed rheumatoid arthritis or other systemic autoimmune disease requiring immunosuppressive therapy or corticosteroids >10 mg/d prednisone equivalent;
• Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis);
• Myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (e.g. angioplasty or stent placement), or deep vein thrombosis/pulmonary embolism within 12 weeks of screening;
• Active cancer (i.e., under current treatment), or cancer requiring treatment in the last 5 years excluding non-melanoma skin cancers or cancers with excellent prognosis (e.g., early stage prostate or breast cancer, carcinoma in situ of the uterine cervix);
• Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYM338 70 mg; BYM338 70 mg intravenous infusion	Drug: bimagrumab; Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.; Other Names: BYM338
Experimental: BYM338 210 mg; BYM338 210 mg intravenous infusion	Drug: bimagrumab; Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.; Other Names: BYM338
Experimental: BYM338 700 mg; BYM338 700 mg intravenous infusion	Drug: bimagrumab; Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.; Other Names: BYM338
Placebo Comparator: Placebo; Placebo intravenous infusion	Other: placebo; Placebo will be administered as an intravenous infusion starting on Day 1 until week 21.; Other Names: 5% dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25	Change from Baseline in total Short Physical Performance Battery (SPPB) Score to week 25; SPPB is a series of six activities involving three domains of physical function - balance, usual walking speed and rising from a chair , is commonly used globally to assess and quantify (score 0-12) lower extremity function and has been shown to predict future adverse health events. A decline of one or more points in the SPPB total score is predictive of a decrease in lower extremity function and future adverse clinical outcomes in older adults, including falls, hospitalizations, institutionalization, incident disability and death	Baseline, week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance	Change from Baseline at Week 25 in the 6 minute walk test (6MWT) distance to measure improvement in physical function	Baseline, week 25
Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters	Change from Baseline to Week 25 in usual Gait speed (GS) over 4 meters Gait speed in this study was assessed as part of the SPPB, over a 4 meter distance of a 6 meter course. This test assessed a person's usual walking speed, which was defined as the speed a person normally walks from one place to another without urgency (e.g., walking down a hallway).	baseline, week 25
Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA)	Change from Baseline to Week 25 on appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) Appendicular skeletal muscle index (ASMI) is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m^2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.	baseline, week 25
Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA)	Change from Baseline to Week 25 on Total lean body mass and appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(LBM at Visit - LBM at Baseline) / LBM at Baseline] * 100.	baseline, week 25

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Rooks D, Swan T, Goswami B, Filosa LA, Bunte O, Panchaud N, Coleman LA, Miller RR, Garcia Garayoa E, Praestgaard J, Perry RG, Recknor C, Fogarty CM, Arai H, Chen LK, Hashimoto J, Chung YS, Vissing J, Laurent D, Petricoul O, Hemsley S, Lach-Trifilieff E, Papanicolaou DA, Roubenoff R. Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2020 Oct 1;3(10):e2020836. doi: 10.1001/jamanetworkopen.2020.20836.

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2014
• Primary Completion (Actual): June 26, 2018
• Study Completion (Actual): June 28, 2018

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 7, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Sarcopenia, muscle wasting, elderly, strength, physical function, muscle, gait speed
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: CBYM338E2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No