A 24-week Off-drug Extension Study in Sarcopenic Elderly Who Completed Treatment in the 6-month Core Study

A 24 Week Off Drug Extension, Parallel Group, Study Assessing Durability of Effect on Skeletal Muscle Strength and Function Following a 6-month Double-blind, Placebo Controlled Study Evaluating Bimagrumab in Older Adults With Sarcopenia (InvestiGAIT Extension)

This extension study was a 24-week off-drug follow-up of the core CBYM338E2202 (NCT ) study and the main objective was to determine the long-term durability of bimagrumab (BYM338) effect after a 6-month treatment period.

Study Overview

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

Detailed Description

Two populations were defined as below:

• Population I: Patients enrolled prior to the protocol amendment 1, who received bimagrumab 70 mg, 210 mg or 700 mg in the core study, were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Patients receiving placebo in the core study continued receiving placebo in the extension study.
• Population II: Patients enrolled after protocol amendment 1, who received bimagrumab 700 mg or placebo in the core study, did not receive study medication in the extension study and were followed-up per schedule defined in this protocol amendment.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • St Albans, Victoria, Australia, 3021
      • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
• Czechia
  • Praha 2, Czechia, 12000
    • Novartis Investigative Site
• Denmark
  • Copenhagen NV, Denmark, 2400
    • Novartis Investigative Site
• France
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Pessac, France, 33604
    • 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, 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
  • 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
• Korea, Republic of
  • Gyeonggi Do
    • Suwon si, Gyeonggi Do, Korea, Republic of, 16499
      • 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
  • 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
• Taiwan
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
• United States
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Novartis Investigative Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criterion:

- Men and postmenopausal women aged 70 years or older that have participated in, and have completed the full study treatment period per protocol (24 weeks/EOT visit) in the preceding core study (CBYM338E2202)

Exclusion criterion:

- Any condition which should have led to treatment discontinuation per protocol in the core study (CBYM338E2202)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Follow-up (arm 1); Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks.	Drug: bimagrumab; bimagrumab low dose bimagrumab moderate dose bimagrumab high dose Patients enrolled prior to the protocol amendment 1 (Population I ), who received bimagrumab in the core study, entered the extension study at Week 25 and were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Study medication was administered as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.; Drug: Placebo; Placebo Patients enrolled prior to the protocol amendment 1 (Population I), who received placebo in core study, entered the extension study at Week 25 and received placebo as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.
No Intervention: Follow-up (arm 2); Patients in Population II received either bimagrumab 700 mg or placebo in the core study and did not receive any investigational treatment in the extension study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49	SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function).	Week 49
Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49	SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function).	Week 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population I: 6-minute Walking Distance (6MWT) at Week 49	The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition.	Week 49
Population II: 6-minute Walking Distance (6MWT) at Week 49	The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition.	Week 49
Population I: Gait Speed at Week 49	Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed.	Week 49
Population II: Gait Speed at Week 49	Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed.	Week 49
Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49	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 (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.	Week 49
Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49	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 (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.	Week 49
Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49	LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect	Week 49
Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49	LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect	Week 49

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2015
• Primary Completion (Actual): December 3, 2018
• Study Completion (Actual): December 3, 2018

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: June 8, 2015
• First Posted (Estimate): June 11, 2015

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Sarcopenia, muscle wasting, elderly, strength, physical function, lean body mass, gait speed
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: CBYM338E2202E1; 2015-000471-27 (EudraCT Number)

Plan for Individual participant data (IPD)

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

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