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

NCT02468674 — Phase 2, Completed, 160 participants, Novartis Pharmaceuticals
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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)

RegistryNCT02468674
StatusCompleted
PhasePhase 2
Study typeInterventional; randomized, single group, masking: quadruple, treatment
Enrollment160 (Actual)
SponsorNovartis Pharmaceuticals (Industry)
ConditionsSarcopenia
Interventionsbimagrumab, Placebo (Drug)
Datesstart 2015-07-22, primary completion 2018-12-03, completion 2018-12-03, first posted 2015-06-11, last updated 2020-06-16
Locations30 sites in United States, Australia, Belgium, Czechia, Denmark, France, Japan, Russia and 4 more countries

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-Summary

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.

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+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.

+Arms and interventions

ArmTypeInterventionsDescription
Follow-up (arm 1)OtherDrug: bimagrumab; Drug: PlaceboPatients 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.
Follow-up (arm 2)No interventionPatients 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.
  • bimagrumab (Drug): 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.
  • Placebo (Drug): 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.

+Outcome measures

Primary outcomes

  • Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 [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).
  • Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 [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).

Secondary outcomes

  • Population I: 6-minute Walking Distance (6MWT) at Week 49 [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.
  • Population II: 6-minute Walking Distance (6MWT) at Week 49 [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.
  • Population I: Gait Speed at Week 49 [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.
  • Population II: Gait Speed at Week 49 [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.
  • Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 [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.
  • Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 [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.
  • Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 [Week 49]: LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect
  • Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 [Week 49]: LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect

+Eligibility

Sex: All, ages: 70 Years to any

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)

+Posted results

Participant flow

MilestonePopulation I: BYM338 700 mgPopulation I BYM338: 700 mg to PlaceboPopulation I: BYM338 210 mgPopulation I BYM338: 210 mg to PlaceboPopulation I: BYM338 70 mgPopulation I: BYM338 70 mg to PlaceboPopulation I: PlaceboPopulation: II BYM338 700 mgPopulation: II Placebo
Started555477156943
Completed455366146540
Not completed100111143

Outcome results

  • Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 (Primary), Mean, Scores on a scale: Population I: BYM338 700 mg 8.8 +/- 3.86; Population I BYM338: 700 mg to Placebo 10.2 +/- 1.92; Population I: BYM338 210 mg 8.0 +/- 2.35; Population I BYM338: 210 mg to Placebo 8.0 +/- 2.65; Population I: BYM338 70 mg 9.5 +/- 2.17; Population I: BYM338 70 mg to Placebo 7.5 +/- 3.78; Population I: Placebo 9.6 +/- 1.83 (p 0.759)
  • Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 (Primary), Mean, Scores on a scale: Population: II BYM338 700 mg 8.6 +/- 2.40; Population: II Placebo 8.8 +/- 1.55 (p 0.839)
  • Population I: 6-minute Walking Distance (6MWT) at Week 49 (Secondary), Mean, meters: Population I: BYM338 700 mg 318.2 +/- 159.55; Population I BYM338: 700 mg to Placebo 354.1 +/- 69.98; Population I: BYM338 210 mg 304.1 +/- 63.05; Population I BYM338: 210 mg to Placebo 361.5 +/- 144.53; Population I: BYM338 70 mg 316.1 +/- 97.87; Population I: BYM338 70 mg to Placebo 273.4 +/- 154.03; Population I: Placebo 368.7 +/- 108.37 (p 0.669)
  • Population II: 6-minute Walking Distance (6MWT) at Week 49 (Secondary), Mean, meters: Population: II BYM338 700 mg 321.2 +/- 105.13; Population: II Placebo 323.1 +/- 96.47 (p 0.367)
  • Population I: Gait Speed at Week 49 (Secondary), Mean, m/sec: Population I: BYM338 700 mg 0.8 +/- 0.35; Population I BYM338: 700 mg to Placebo 1.0 +/- 0.18; Population I: BYM338 210 mg 0.9 +/- 0.17; Population I BYM338: 210 mg to Placebo 1.1 +/- 0.24; Population I: BYM338 70 mg 0.9 +/- 0.15; Population I: BYM338 70 mg to Placebo 0.7 +/- 0.35; Population I: Placebo 0.8 +/- 0.18 (p 0.875)
  • Population II: Gait Speed at Week 49 (Secondary), Mean, m/sec: Population: II BYM338 700 mg 0.9 +/- 0.24; Population: II Placebo 0.9 +/- 0.17 (p 0.395)
  • Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 (Secondary), Geometric mean, kg/m^2: Population I: BYM338 700 mg 6.6 +/- 7.22; Population I BYM338: 700 mg to Placebo 6.0 +/- 14.05; Population I: BYM338 210 mg 6.1 +/- 8.08; Population I BYM338: 210 mg to Placebo 5.8 +/- 15.08; Population I: BYM338 70 mg 5.9 +/- 14.19; Population I: BYM338 70 mg to Placebo 5.2 +/- 14.85; Population I: Placebo 5.6 +/- 15.21 (p 0.120)
  • Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 (Secondary), Geometric mean, kg/m^2: Population: II BYM338 700 mg 5.6 +/- 14.36; Population: II Placebo 5.5 +/- 12.46 (p 1.000)
  • Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 (Secondary), Geometric mean, kg: Population I: BYM338 700 mg 41.4 +/- 21.11; Population I BYM338: 700 mg to Placebo 34.0 +/- 17.76; Population I: BYM338 210 mg 35.5 +/- 15.39; Population I BYM338: 210 mg to Placebo 32.6 +/- 25.23; Population I: BYM338 70 mg 34.9 +/- 21.16; Population I: BYM338 70 mg to Placebo 34.0 +/- 18.47; Population I: Placebo 32.6 +/- 17.95 (p 0.084)
  • Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 (Secondary), Geometric mean, kg: Population: II BYM338 700 mg 34.9 +/- 25.01; Population: II Placebo 33.7 +/- 20.40 (p 1.000)

Adverse events

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum treatment duration of 24 weeks

ArmDeathsSerious adverse eventsOther adverse events
Population I BYM338 700 mg0/5 (0.0%)0/5 (0.0%)4/5 (80.0%)
Population I BYM338 700 mg to Placebo0/5 (0.0%)1/5 (20.0%)4/5 (80.0%)
Population I BYM338 210 mg0/5 (0.0%)0/5 (0.0%)3/5 (60.0%)
Population I BYM338 210 mg to Placebo0/4 (0.0%)0/4 (0.0%)2/4 (50.0%)
Population I BYM338 70 mg0/7 (0.0%)0/7 (0.0%)5/7 (71.4%)
Population I BYM338 70 mg to Placebo0/7 (0.0%)2/7 (28.6%)3/7 (42.9%)
Population I Placebo0/15 (0.0%)2/15 (13.3%)11/15 (73.3%)
Population: II BYM338 700 mg0/69 (0.0%)0/69 (0.0%)0/69 (0.0%)
Population: II Placebo0/43 (0.0%)0/43 (0.0%)0/43 (0.0%)

Serious adverse events by term

TermOrgan systemPopulation I BYM338 700 mgPopulation I BYM338 700 mg to PlaceboPopulation I BYM338 210 mgPopulation I BYM338 210 mg to PlaceboPopulation I BYM338 70 mgPopulation I BYM338 70 mg to PlaceboPopulation I PlaceboPopulation: II BYM338 700 mgPopulation: II Placebo
CataractEye disorders0/50/50/50/40/70/71/150/690/43
FallInjury, poisoning and procedural complications0/50/50/50/40/71/70/150/690/43
Lumbar vertebral fractureInjury, poisoning and procedural complications0/50/50/50/40/71/70/150/690/43
OsteoarthritisMusculoskeletal and connective tissue disorders0/50/50/50/40/71/70/150/690/43
Gallbladder cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/50/50/50/40/71/70/150/690/43
Pancreatic carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/50/50/50/40/70/71/150/690/43
SeizureNervous system disorders0/51/50/50/40/70/70/150/690/43

Other adverse events by term

TermOrgan systemPopulation I BYM338 700 mgPopulation I BYM338 700 mg to PlaceboPopulation I BYM338 210 mgPopulation I BYM338 210 mg to PlaceboPopulation I BYM338 70 mgPopulation I BYM338 70 mg to PlaceboPopulation I PlaceboPopulation: II BYM338 700 mgPopulation: II Placebo
Bundle branch block leftCardiac disorders0/50/50/50/40/70/71/150/690/43
Ventricular extrasystolesCardiac disorders0/50/50/51/40/70/70/150/690/43
Dry eyeEye disorders0/50/51/50/40/70/70/150/690/43
Eye irritationEye disorders0/50/50/50/40/70/71/150/690/43
Macular degenerationEye disorders0/50/50/50/41/70/70/150/690/43
Abdominal discomfortGastrointestinal disorders0/50/50/50/40/71/70/150/690/43
Chronic gastritisGastrointestinal disorders1/50/50/50/40/70/70/150/690/43
ConstipationGastrointestinal disorders0/50/50/50/41/71/70/150/690/43
Gastrooesophageal reflux diseaseGastrointestinal disorders0/50/50/50/40/70/71/150/690/43
Large intestine polypGastrointestinal disorders1/50/50/50/40/70/70/150/690/43
NauseaGastrointestinal disorders1/50/50/50/40/70/71/150/690/43
VomitingGastrointestinal disorders1/50/50/50/40/70/70/150/690/43
FatigueGeneral disorders0/51/50/50/40/70/71/150/690/43
Influenza like illnessGeneral disorders0/50/50/50/40/70/71/150/690/43
Non-cardiac chest painGeneral disorders0/50/50/50/40/70/71/150/690/43
Peripheral swellingGeneral disorders0/50/51/50/40/70/70/150/690/43
Hepatic function abnormalHepatobiliary disorders0/50/50/50/40/70/71/150/690/43
CystitisInfections and infestations0/50/50/50/40/70/71/150/690/43
GastroenteritisInfections and infestations0/50/50/51/40/70/70/150/690/43
GingivitisInfections and infestations0/50/50/50/40/71/70/150/690/43
Herpes zosterInfections and infestations0/50/50/50/42/70/71/150/690/43
NasopharyngitisInfections and infestations0/51/50/50/40/70/71/150/690/43
PneumoniaInfections and infestations0/50/51/50/40/70/70/150/690/43
RhinitisInfections and infestations1/50/50/50/40/70/70/150/690/43
SinusitisInfections and infestations0/50/51/50/40/70/70/150/690/43
Tinea versicolourInfections and infestations0/50/50/50/41/70/70/150/690/43
Upper respiratory tract infectionInfections and infestations0/50/50/50/40/70/71/150/690/43
Urinary tract infectionInfections and infestations0/50/50/50/40/71/71/150/690/43
Arthropod biteInjury, poisoning and procedural complications0/50/50/50/40/70/71/150/690/43
ContusionInjury, poisoning and procedural complications0/50/50/50/40/70/72/150/690/43
FallInjury, poisoning and procedural complications1/51/50/51/42/70/76/150/690/43
Head injuryInjury, poisoning and procedural complications0/50/50/50/40/70/71/150/690/43
Ligament sprainInjury, poisoning and procedural complications0/50/50/50/40/71/71/150/690/43
Muscle contusionInjury, poisoning and procedural complications0/50/50/50/41/70/70/150/690/43
Skin abrasionInjury, poisoning and procedural complications0/50/50/51/40/70/70/150/690/43
Aspartate aminotransferase increasedInvestigations1/50/50/50/40/70/70/150/690/43
Body mass index decreasedInvestigations1/50/50/50/40/70/70/150/690/43
Lipase increasedInvestigations0/51/50/50/40/70/70/150/690/43
HyperkalaemiaMetabolism and nutrition disorders0/50/50/50/40/70/71/150/690/43
ArthralgiaMusculoskeletal and connective tissue disorders1/50/50/50/40/70/71/150/690/43
Back painMusculoskeletal and connective tissue disorders1/50/50/50/42/71/70/150/690/43
Muscle spasmsMusculoskeletal and connective tissue disorders0/50/50/50/41/70/70/150/690/43
Musculoskeletal painMusculoskeletal and connective tissue disorders0/51/50/50/40/70/70/150/690/43
Pain in extremityMusculoskeletal and connective tissue disorders0/50/50/50/40/70/72/150/690/43
TenosynovitisMusculoskeletal and connective tissue disorders0/50/50/50/41/70/70/150/690/43
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/50/50/50/40/70/70/150/690/43
Skin papillomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/50/50/50/40/70/70/150/690/43
DizzinessNervous system disorders0/50/51/50/40/70/70/150/690/43
HeadacheNervous system disorders0/50/50/50/40/70/71/150/690/43
PresyncopeNervous system disorders0/50/50/50/40/70/71/150/690/43
Device looseningProduct Issues0/50/51/50/40/70/70/150/690/43
Anxiety disorderPsychiatric disorders0/50/50/50/40/71/70/150/690/43
NephrolithiasisRenal and urinary disorders1/50/50/50/40/70/70/150/690/43
Renal cystRenal and urinary disorders1/50/50/50/40/70/70/150/690/43
Prostatic dysplasiaReproductive system and breast disorders0/50/50/51/40/70/70/150/690/43
DyspnoeaRespiratory, thoracic and mediastinal disorders0/50/50/50/40/70/71/150/690/43
Skin ulcerSkin and subcutaneous tissue disorders0/50/50/50/40/70/71/150/690/43
HypertensionVascular disorders0/50/50/50/40/71/70/150/690/43

+Locations (30)

FacilityCityCountryStatus
Novartis Investigative SiteMiami Lakes, FloridaUnited States
Novartis Investigative SiteGainesville, GeorgiaUnited States
Novartis Investigative SiteSpartanburg, South CarolinaUnited States
Novartis Investigative SiteSan Antonio, TexasUnited States
Novartis Investigative SiteMadison, WisconsinUnited States
Novartis Investigative SiteSt Albans, VictoriaAustralia
Novartis Investigative SiteBrusselsBelgium
Novartis Investigative SitePragueCzechia
Novartis Investigative SiteCopenhagen NVDenmark
Novartis Investigative SiteMontpellierFrance
Novartis Investigative SitePessacFrance
Novartis Investigative SiteŌbu, Aichi-kenJapan
Novartis Investigative SiteToyohashi, Aichi-kenJapan
Novartis Investigative SiteMizunami, GifuJapan
Novartis Investigative SiteNara, NaraJapan
Novartis Investigative SiteKawachi-Nagano, OsakaJapan
Novartis Investigative SiteKitaadachigun Inamachi, SaitamaJapan
Novartis Investigative SiteKitamoto, SaitamaJapan
Novartis Investigative SiteItabashi Ku, TokyoJapan
Novartis Investigative SiteKiyose, TokyoJapan
Novartis Investigative SiteKoto-ku, TokyoJapan
Novartis Investigative SiteMoscowRussia
Novartis Investigative SiteMoscowRussia
Novartis Investigative SiteSaint PetersburgRussia
Novartis Investigative SiteYaroslavlRussia
Novartis Investigative SiteSuwon, Gyeonggi-doSouth Korea
Novartis Investigative SiteAlbacete, Castille-La ManchaSpain
Novartis Investigative SiteGetafe, MadridSpain
Novartis Investigative SiteGenevaSwitzerland
Novartis Investigative SiteTaipeiTaiwan

+Study documents

+Investigators

  • Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals

+Funding

NIH grants: 2015

My Notes