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

NCT02152761 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CBYM338D22012013-003439-31
• Study Type: interventional
• Target: 251
• Locations: 18 countries
• Sites: 52

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.

Conditions

Muscle Wasting (Atrophy) After Hip Fracture Surgery

Keywords

bimagrumab; BYM338; hip fracture; elderly; controlled clinical trial; randomized; muscle wasting; atrophy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change From Baseline in Gait Speed at Week 24 (Meters/Sec)

  Baseline, Week 24

• Change From Baseline in Short Physical Performance Battery at Weeks 24

  Week 24

• Incidence of Falls up to Week 48

  Up to Week 48

Study Arms (4)

bimagrumab 700 mg

EXPERIMENTAL

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 210 mg

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Bimagrumab 70 mg

EXPERIMENTAL

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

Interventions

bimagrumab DRUG

Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.

Also known as: BYM338

Bimagrumab 70 mg; bimagrumab 210 mg; bimagrumab 700 mg

placebo OTHER

Matching placebo was administered as intravenous infusion starting on Day 1 until week 20.

placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (53)

Novartis Investigative Site

Phoenix, Arizona, 85023, United States

Location

Novartis Investigative Site

El Cajon, California, 92020, United States

Location

Novartis Investigative Site

Denver, Colorado, 80210, United States

Location

Novartis Investigative Site

Gainesville, Georgia, 30501, United States

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Novartis Investigative Site

Rochester, Minnesota, 55905, United States

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Novartis Investigative Site

New York, New York, 10021, United States

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Novartis Investigative Site

Ciudad Autonoma de Bs As, C1128AAF, Argentina

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Novartis Investigative Site

Bedford Park, South Australia, 5041, Australia

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Novartis Investigative Site

Graz, 80 10, Austria

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Novartis Investigative Site

Bruges, 8000, Belgium

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Novartis Investigative Site

Genk, 3600, Belgium

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Novartis Investigative Site

Ghent, 9000, Belgium

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Novartis Investigative Site

Santiago, 838 0456, Chile

Location

Novartis Investigative Site

Cali, Valle del Cauca Department, Colombia

Location

Novartis Investigative Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Brno, Czech Republic, 66250, Czechia

Location

Novartis Investigative Site

Hradec Králové, Czech Republic, 500 05, Czechia

Location

Novartis Investigative Site

Pardubice, Czech Republic, 532 03, Czechia

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Novartis Investigative Site

Pilsen, Czech Republic, 30450, Czechia

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Novartis Investigative Site

Prague, Czech Republic, 150 06, Czechia

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Novartis Investigative Site

Prague, 100 34, Czechia

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Bad Abbach, 93077, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Magdeburg, 39110, Germany

Location

Novartis Investigative Site

Würzburg, 97074, Germany

Location

Novartis Investigative Site

Budapest, 1062, Hungary

Location

Novartis Investigative Site

Budapest, 1125, Hungary

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Novartis Investigative Site

Hatvan, 3000, Hungary

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Novartis Investigative Site

Nishinomiya, Hyōgo, 662-0918, Japan

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Novartis Investigative Site

Kamakura, Kanagawa, 247-8533, Japan

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Novartis Investigative Site

Kochi, Kochi, 780-8522, Japan

Location

Novartis Investigative Site

Kumamoto, Kumamoto, 862-0976, Japan

Location

Novartis Investigative Site

Okayama, Okayama-ken, 701-1192, Japan

Location

Novartis Investigative Site

Toyama, Toyama, 939-8511, Japan

Location

Novartis Investigative Site

Aguascalientes, 20127, Mexico

Location

Novartis Investigative Site

San Luis Potosí City, 78200, Mexico

Location

Novartis Investigative Site

Saint Petersburg, 190103, Russia

Location

Novartis Investigative Site

Saint Petersburg, 196143, Russia

Location

Novartis Investigative Site

Sestroretsk, 197706, Russia

Location

Novartis Investigative Site

Yaroslavl, 150003, Russia

Location

Novartis Investigative Site

Seville, Andalusia, 41014, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28049, Spain

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Novartis Investigative Site

Geneva, 1211, Switzerland

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Novartis Investigative Site

Kaohsiung City, 82445, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

Location

Novartis Investigative Site

Taoyuan District, 33305, Taiwan

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Bath, BA1 3NG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36098133 DERIVED

MeSH Terms

Conditions

Muscular Atrophy; Atrophy; Hip Fractures

Interventions

bimagrumab

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries

Limitations and Caveats

As there were no statistically significant improvements in functional measures (i.e. gait speed, SPPB) at week 24, the need to test for sustained improvement at wk 48 became irrelevant. So, wk 48 treatment differences were not evaluated

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 (862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, interventional, multicenter, placebo-controlled, phase IIa/IIb trial in patients

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: June 2, 2014
• Study Start: September 16, 2014
• Primary Completion: May 14, 2018
• Study Completion: October 25, 2018
• Last Updated: August 19, 2020
• Results First Posted: August 19, 2020

Record last verified: 2020-08

Locations

AU (1); CO (2); RU (4); ME (2); HU (3); US (6); TW (3); AR (1); GB (1); FR (2); JP (6); BE (3); CL (1); ES (4); CZ (6); DE (4); CH (1); TU (2)