Dose Range Finding Study of Bimagrumab in Sarcopenia

NCT02333331 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CBYM338E2202
• Study Type: interventional
• Target: 217
• Locations: 13 countries
• Sites: 58

Brief Summary

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.

Conditions

Sarcopenia

Keywords

Sarcopenia, muscle wasting, elderly, strength, physical function, muscle, gait speed

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance

  Baseline, week 25

• Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters

  baseline, week 25

• Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA)

  baseline, week 25

• Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA)

  baseline, week 25

Study Arms (4)

BYM338 70 mg

EXPERIMENTAL

BYM338 70 mg intravenous infusion

Drug: bimagrumab

BYM338 210 mg

EXPERIMENTAL

BYM338 210 mg intravenous infusion

Drug: bimagrumab

BYM338 700 mg

EXPERIMENTAL

BYM338 700 mg intravenous infusion

Drug: bimagrumab

Placebo

PLACEBO COMPARATOR

Placebo intravenous infusion

Other: placebo

Interventions

bimagrumab DRUG

Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.

Also known as: BYM338

BYM338 210 mg; BYM338 70 mg; BYM338 700 mg

placebo OTHER

Placebo will be administered as an intravenous infusion starting on Day 1 until week 21.

Also known as: 5% dextrose

Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (58)

Novartis Investigative Site

Little Rock, Arkansas, 72205, United States

Location

Novartis Investigative Site

Cypress, California, 90630, United States

Location

Novartis Investigative Site

La Jolla, California, 92093-9405, United States

Location

Novartis Investigative Site

Farmington, Connecticut, 06030-5215, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32611, United States

Location

Novartis Investigative Site

Miami, Florida, 33143, United States

Location

Novartis Investigative Site

Miami Lakes, Florida, 33014, United States

Location

Novartis Investigative Site

Orlando, Florida, 32804, United States

Location

Novartis Investigative Site

Gainesville, Georgia, 30501, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigative Site

High Point, North Carolina, 27262, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

Novartis Investigative Site

Spartanburg, South Carolina, 29303, United States

Location

Novartis Investigative Site

Mesquite, Texas, 75150, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53706, United States

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

St Albans, Victoria, 3021, Australia

Location

Novartis Investigative Site

Brussels, 1090, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Brno, 62500, Czechia

Location

Novartis Investigative Site

Opava, 74601, Czechia

Location

Novartis Investigative Site

Prague, 12000, Czechia

Location

Novartis Investigative Site

Copenhagen, 2100, Denmark

Location

Novartis Investigative Site

Copenhagen NV, 2400, Denmark

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Paris, 75013, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Toulouse, 31052, France

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Würzburg, 97074, Germany

Location

Novartis Investigative Site

Ōbu, Aichi-ken, 474-8511, Japan

Location

Novartis Investigative Site

Toyohashi, Aichi-ken, 440-8510, Japan

Location

Novartis Investigative Site

Mizunami, Gifu, 509 6134, Japan

Location

Novartis Investigative Site

Nara, Nara, 630-8581, Japan

Location

Novartis Investigative Site

Kawachi-Nagano, Osaka, 586-8521, Japan

Location

Novartis Investigative Site

Kitaadachigun Inamachi, Saitama, 362-0806, Japan

Location

Novartis Investigative Site

Kitamoto, Saitama, 364-8501, Japan

Location

Novartis Investigative Site

Yoshinogawa, Tokushima, 776-8585, Japan

Location

Novartis Investigative Site

Itabashi Ku, Tokyo, 173 0015, Japan

Location

Novartis Investigative Site

Kiyose, Tokyo, 204-0021, Japan

Location

Novartis Investigative Site

Koto-ku, Tokyo, 136-0075, Japan

Location

Novartis Investigative Site

Musashimurayama, Tokyo, 208-0011, Japan

Location

Novartis Investigative Site

Moscow, 101990, Russia

Location

Novartis Investigative Site

Moscow, 117997, Russia

Location

Novartis Investigative Site

Saint Petersburg, 190068, Russia

Location

Novartis Investigative Site

Yaroslavl, 150003, Russia

Location

Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

Location

Novartis Investigative Site

Suwon, Gyeonggi-do, 16499, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 02447, South Korea

Location

Novartis Investigative Site

Albacete, Castille-La Mancha, 02006, Spain

Location

Novartis Investigative Site

Getafe, Madrid, 28905, Spain

Location

Novartis Investigative Site

Barcelona, 08024, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Basel, CH, 4002, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

Taipei, 11217, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 33074327 DERIVED

Related Links

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

MeSH Terms

Conditions

Sarcopenia; Muscular Atrophy

Interventions

bimagrumab; Glucose

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

8627788300

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

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: January 7, 2015
• Study Start: December 9, 2014
• Primary Completion: June 26, 2018
• Study Completion: June 28, 2018
• Last Updated: January 5, 2021
• Results First Posted: August 6, 2019

Record last verified: 2019-07

Locations

JP (12); KR (3); CZ (3); CH (2); TW (1); DK (2); DE (2); RU (4); ES (4); FR (4); US (17); AU (2); BE (2)