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

Primary Purpose

Muscle Wasting (Atrophy) After Hip Fracture Surgery

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bimagrumab
placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscle Wasting (Atrophy) After Hip Fracture Surgery focused on measuring bimagrumab, BYM338, hip fracture, elderly, controlled clinical trial, randomized, muscle wasting, atrophy

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

bimagrumab 700 mg

bimagrumab 210 mg

placebo

Bimagrumab 70 mg

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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

Full Information

First Posted
May 8, 2014
Last Updated
August 9, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02152761
Brief Title
Study of Efficacy and Safety of Bimagrumab in Patients After Hip Fracture Surgery
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
September 16, 2014 (Actual)
Primary Completion Date
May 14, 2018 (Actual)
Study Completion Date
October 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Wasting (Atrophy) After Hip Fracture Surgery
Keywords
bimagrumab, BYM338, hip fracture, elderly, controlled clinical trial, randomized, muscle wasting, atrophy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized, interventional, multicenter, placebo-controlled, phase IIa/IIb trial in patients
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
251 (Actual)

8. Arms, Groups, and Interventions

Arm Title
bimagrumab 700 mg
Arm Type
Experimental
Arm Description
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
Arm Title
bimagrumab 210 mg
Arm Type
Experimental
Arm Description
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
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Bimagrumab 70 mg
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
bimagrumab
Other Intervention Name(s)
BYM338
Intervention Description
Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Matching placebo was administered as intravenous infusion starting on Day 1 until week 20.
Primary Outcome Measure Information:
Title
Change From Baseline in Total Lean Body Mass Measured by DXA (Dual-energy X-ray Absorptiometry) at Weeks 12 and 24
Description
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
Time Frame
baseline, weeks 12 and 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Gait Speed at Week 24 (Meters/Sec)
Description
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
Time Frame
Baseline, Week 24
Title
Change From Baseline in Short Physical Performance Battery at Weeks 24
Description
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
Time Frame
Week 24
Title
Incidence of Falls up to Week 48
Description
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
Time Frame
Up to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Novartis Investigative Site
City
El Cajon
State/Province
California
ZIP/Postal Code
92020
Country
United States
Facility Name
Novartis Investigative Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
Novartis Investigative Site
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Novartis Investigative Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Novartis Investigative Site
City
Ciudad Autonoma de Bs As
ZIP/Postal Code
C1128AAF
Country
Argentina
Facility Name
Novartis Investigative Site
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5041
Country
Australia
Facility Name
Novartis Investigative Site
City
Graz
ZIP/Postal Code
80 10
Country
Austria
Facility Name
Novartis Investigative Site
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Santiago
ZIP/Postal Code
838 0456
Country
Chile
Facility Name
Novartis Investigative Site
City
Cali
State/Province
Valle Del Cauca
Country
Colombia
Facility Name
Novartis Investigative Site
City
Barranquilla
Country
Colombia
Facility Name
Novartis Investigative Site
City
Brno
State/Province
Czech Republic
ZIP/Postal Code
66250
Country
Czechia
Facility Name
Novartis Investigative Site
City
Hradec Kralove
State/Province
Czech Republic
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Novartis Investigative Site
City
Pardubice
State/Province
Czech Republic
ZIP/Postal Code
532 03
Country
Czechia
Facility Name
Novartis Investigative Site
City
Plzen
State/Province
Czech Republic
ZIP/Postal Code
30450
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha 5
State/Province
Czech Republic
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Novartis Investigative Site
City
Bad Abbach
ZIP/Postal Code
93077
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Magdeburg
ZIP/Postal Code
39110
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97074
Country
Germany
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1062
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Novartis Investigative Site
City
Hatvan
ZIP/Postal Code
3000
Country
Hungary
Facility Name
Novartis Investigative Site
City
Nishinomiya-city
State/Province
Hyogo
ZIP/Postal Code
662-0918
Country
Japan
Facility Name
Novartis Investigative Site
City
Kamakura-city
State/Province
Kanagawa
ZIP/Postal Code
247-8533
Country
Japan
Facility Name
Novartis Investigative Site
City
Kochi-city
State/Province
Kochi
ZIP/Postal Code
780-8522
Country
Japan
Facility Name
Novartis Investigative Site
City
Kumamoto-city
State/Province
Kumamoto
ZIP/Postal Code
862-0976
Country
Japan
Facility Name
Novartis Investigative Site
City
Okayama city
State/Province
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
Novartis Investigative Site
City
Toyama-City
State/Province
Toyama
ZIP/Postal Code
939-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Aguascalientes
ZIP/Postal Code
20127
Country
Mexico
Facility Name
Novartis Investigative Site
City
San Luis Potosi
ZIP/Postal Code
78200
Country
Mexico
Facility Name
Novartis Investigative Site
City
Saint-Petersburg
ZIP/Postal Code
196143
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Sestroretsk
ZIP/Postal Code
197706
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St.- Petersburg
ZIP/Postal Code
190103
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41014
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28049
Country
Spain
Facility Name
Novartis Investigative Site
City
Genève 14
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
82445
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taoyuan
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Novartis Investigative Site
City
Bath
ZIP/Postal Code
BA1 3NG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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
Citations:
PubMed Identifier
36098133
Citation
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.
Results Reference
derived

Learn more about this trial

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

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