Study of Efficacy and Safety of Bimagrumab in Patients After Hip Fracture Surgery

A 24-week Double-blind Treatment and 24-week Follow-up, Randomized, Multicenter, Placebo-controlled, Phase IIa/IIb Study to Evaluate Safety and Efficacy of i.v. Bimagrumab on Total Lean Body Mass and Physical Performance in Patients After Surgical Treatment of Hip Fracture

The purpose of this study was to assess if bimagrumab is safe and effective in patients with muscle wasting (atrophy) after hip fracture surgery.

Study Overview

• Status: Completed
• Conditions: Muscle Wasting (Atrophy) After Hip Fracture Surgery
• Intervention / Treatment: Drug: bimagrumab; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Bs As, Argentina, C1128AAF
    • Novartis Investigative Site
• Australia
  • South Australia
    • Bedford Park, South Australia, Australia, 5041
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 80 10
    • Novartis Investigative Site
• Belgium
  • Brugge, Belgium, 8000
    • Novartis Investigative Site
  • Genk, Belgium, 3600
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
• Chile
  • Santiago, Chile, 838 0456
    • Novartis Investigative Site
• Colombia
  • Barranquilla, Colombia
    • Novartis Investigative Site
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia
      • Novartis Investigative Site
• Czechia
  • Praha 10, Czechia, 100 34
    • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 66250
      • Novartis Investigative Site
    • Hradec Kralove, Czech Republic, Czechia, 500 05
      • Novartis Investigative Site
    • Pardubice, Czech Republic, Czechia, 532 03
      • Novartis Investigative Site
    • Plzen, Czech Republic, Czechia, 30450
      • Novartis Investigative Site
    • Praha 5, Czech Republic, Czechia, 150 06
      • Novartis Investigative Site
• France
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
• Germany
  • Bad Abbach, Germany, 93077
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Würzburg, Germany, 97074
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1125
    • Novartis Investigative Site
  • Budapest, Hungary, 1062
    • Novartis Investigative Site
  • Hatvan, Hungary, 3000
    • Novartis Investigative Site
• Japan
  • Hyogo
    • Nishinomiya-city, Hyogo, Japan, 662-0918
      • Novartis Investigative Site
  • Kanagawa
    • Kamakura-city, Kanagawa, Japan, 247-8533
      • Novartis Investigative Site
  • Kochi
    • Kochi-city, Kochi, Japan, 780-8522
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto-city, Kumamoto, Japan, 862-0976
      • Novartis Investigative Site
  • Okayama
    • Okayama city, Okayama, Japan, 701-1192
      • Novartis Investigative Site
  • Toyama
    • Toyama-City, Toyama, Japan, 939-8511
      • Novartis Investigative Site
• Mexico
  • Aguascalientes, Mexico, 20127
    • Novartis Investigative Site
  • San Luis Potosi, Mexico, 78200
    • Novartis Investigative Site
• Russian Federation
  • Saint-Petersburg, Russian Federation, 196143
    • Novartis Investigative Site
  • Sestroretsk, Russian Federation, 197706
    • Novartis Investigative Site
  • St.- Petersburg, Russian Federation, 190103
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28049
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Switzerland
  • Genève 14, Switzerland, 1211
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• Turkey
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Novartis Investigative Site
  • California
    • El Cajon, California, United States, 92020
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • Novartis Investigative Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Novartis Investigative Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10021
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Must have X-ray confirmed successful hip fracture repair; Must have completed surgical wound healing; Ability to walk a specified distance with or without a walking aid; Must weigh at least 35 kg.

Exclusion Criteria:

Must not have history of any other lower limb fractures in the past 6 months; Must not have certain cardiovascular conditions; Must not have a chronic active infection (e.g. HIV, hepatitis B or C, etc); Must not have used high-dose corticosteroid medications for at least 3 months in the past year;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: bimagrumab 700 mg; Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria were treated with the bimagrumab high dose administered via intravenous infusion starting Day 1 until Week 20	Drug: bimagrumab; Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.; Other Names: BYM338
EXPERIMENTAL: bimagrumab 210 mg; Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria were treated with the bimagrumab medium dose administered via intravenous infusion starting Day 1 until Week 20	Drug: bimagrumab; Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.; Other Names: BYM338
PLACEBO_COMPARATOR: placebo; Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria received matching placbo administered via intravenous infusion starting Day 1 until Week 20	Other: placebo; Matching placebo was administered as intravenous infusion starting on Day 1 until week 20.
EXPERIMENTAL: Bimagrumab 70 mg; Approximately 35 patients who met all inclusion criteria and none of the exclusion criteria were treated with bimagrumad low dose administered via intravenous infusion starting Day 1 until Week 20	Drug: bimagrumab; Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.; Other Names: BYM338

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Lean Body Mass Measured by DXA (Dual-energy X-ray Absorptiometry) at Weeks 12 and 24	Mixed Model for Repeated Measures (MMRM) of change from baseline in total LBM (kg) by treatment and visit To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least three doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg has been added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed	baseline, weeks 12 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Gait Speed at Week 24 (Meters/Sec)	Mixed Model for Repeated Measures (MMRM) of change from baseline in derived gait speed (m/sec) by treatment and visit To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg was added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed	Baseline, Week 24
Change From Baseline in Short Physical Performance Battery at Weeks 24	MMRM change from baseline in total score by treatment & visit to Week 24 in physical performance measured by Short Physical Performance Battery (SPPB) that evaluates lower extremity function. Score range is 0 (worst performance) to 12 (best) to assess dose-response relationship of bimagrumab & facilitate adequate dose selection for future phase III studies, without need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from non- or minimally effective dose to a dose where maximal efficacy was expected. Original study was initiated with only 2 doses, therefore, lower 70mg arm was added to this study, changing randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, 210mg, or 700mg. Since 70mg dose was expected to show suboptimal efficacy, fewer patients were randomized to this group & it was used only for dose response modelling & not hypothesis testing. Consequently, no efficacy evaluation for 70mg were performed	Week 24
Incidence of Falls up to Week 48	Group falls rate The frequency of having at least one fall up to Week 48 was summarized by treatment groups Incidence of falls was calculated for each arm up to Week 48. The ratio of these fall rates versus Placebo were calculated and presented as the Falls Rate Ratio. As mentioned in comment 5.1 above, the Falls Rate Ratio for Placebo does not apply because it would entail comparing the group to itself	Up to Week 48

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hofbauer LC, Witvrouw R, Varga Z, Shiota N, Cremer M, Tanko LB, Rooks D, Auberson LZ, Arkuszewski M, Fretault N, Schubert-Tennigkeit AA, Papanicolaou DA, Recknor C. Bimagrumab to improve recovery after hip fracture in older adults: a multicentre, double-blind, randomised, parallel-group, placebo-controlled, phase 2a/b trial. Lancet Healthy Longev. 2021 May;2(5):e263-e274. doi: 10.1016/S2666-7568(21)00084-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 16, 2014
• Primary Completion (ACTUAL): May 14, 2018
• Study Completion (ACTUAL): October 25, 2018

Study Registration Dates

• First Submitted: May 8, 2014
• First Submitted That Met QC Criteria: May 30, 2014
• First Posted (ESTIMATE): June 2, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: elderly; atrophy; randomized; hip fracture; controlled clinical trial; muscle wasting; bimagrumab; BYM338
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Leg Injuries; Nutrition Disorders; Body Weight; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Body Weight Changes; Femoral Fractures; Hip Injuries; Emaciation; Weight Loss; Muscular Atrophy; Fractures, Bone; Hip Fractures; Atrophy; Wasting Syndrome; Cachexia
• Other Study ID Numbers: CBYM338D2201; 2013-003439-31 (EUDRACT_NUMBER)

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