BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia

NCT01669174 | Completed Phase 2 Results DMC

• 2 other identifiers: CBYM338X22042011-000461-12
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 9

Brief Summary

This study will assess the pharmacodynamics, pharmacokinetics, safety and tolerability of BYM338 in patients with COPD and cachexia. The primary outcome will be a change in thigh muscle volume compared to placebo. The study will last for approximately 24 weeks.

Conditions

Chronic Obstructive Pulmonary Disease (COPD) With Cachexia

Keywords

Chronic Obstructive Pulmonary Disease; COPD; cachexia; muscle wasting

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24

  Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.

  Baseline, Weeks 4, 8, 16, 24

Secondary Outcomes (4)

• Change in 6 Minute Walk Distance Compared to Placebo

  Baseline, Weeks 4, 8, 16, 24

• Maximum Observed Serum Concentration (Cmax)

  0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose

• Time to Reach the Maximum Concentration After Drug Administration (Tmax)

  24 weeks

• AUC0-56 and AUClast

  0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose

Study Arms (2)

BYM338

EXPERIMENTAL

Drug: BYM338

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Placebo

BYM338 DRUG

BYM338

BYM338

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Males and females ages 40 to 80 years
• Smoking history of at least 10 pack-years
• Diagnosis of COPD according to GOLD guidelines (GOLD, 2010), with a post-bronchodilator FEV¬1 \< 80% predicted and FEV1/FVC ratio \< 0.70
• BMI \<20 kg/m2 or skeletal muscle mass index by DXA \< 7.25 kg/m2 for men or \<5.45 kg/m2 for women.
• In general stable health, including managed COPD, by past medical history, physical examination, vital signs at baseline as determined by the investigator.

You may not qualify if:

• Patients with MRC dyspnoea grade 5 (i.e. patients too breathless to leave the house or breathless when dressing)
• Plans for lung transplantation or lung reduction surgery within four months of enrollment
• Patients participating in a formal pulmonary rehabilitation program within 3 months of dosing
• History of malignancy of any organ system (other than excised non-melanomatous carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Diseases other than cancer known to cause cachexia or muscle atrophy, including but not limited to congestive heart failure of any stage, chronic kidney disease (estimated GFR \< 30 mL/min using the MDRD equation), rheumatoid arthritis, primary myopathy, stroke, HIV infection, tuberculosis or other chronic infection, uncontrolled diabetes mellitus, etc.
• Inflammatory bowel disease, celiac disease, short bowel syndrome, pancreatic insufficiency
• Use of any prescription drugs known to affect muscle mass, including androgen supplements, anti-androgens (such as LHRH agonists), anti-estrogens (tamoxifen, etc.) recombinant human growth hormone (rhGH), insulin, oral beta agonists, megestrol acetate, dronabinol, metformin, etc.
• Hemoglobin concentration below 11.0 g/dL at screening.
• Liver disease or liver injury.
• Use of other investigational drugs at the time of enrollment, or within 30 days and for any other limitation of participation in an investigational trial based on local regulations.
• Women of child-bearing potential.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Torrance, California, 90502, United States

Location

Novartis Investigative Site

Savannah, Georgia, 31419, United States

Location

Novartis Investigative Site

Normal, Illinois, 61761, United States

Location

Novartis Investigative Site

Missoula, Montana, 59808, United States

Location

Novartis Investigative Site

Spartanburg, South Carolina, 29303, United States

Location

Novartis Investigative Site

Maastricht, 6211, Netherlands

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

Novartis Investigative Site

London, SW 6NP, United Kingdom

Location

Novartis Investigative Site

Machester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Polkey MI, Praestgaard J, Berwick A, Franssen FME, Singh D, Steiner MC, Casaburi R, Tillmann HC, Lach-Trifilieff E, Roubenoff R, Rooks DS. Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial. Am J Respir Crit Care Med. 2019 Feb 1;199(3):313-320. doi: 10.1164/rccm.201802-0286OC.

  PMID: 30095981 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cachexia; Muscular Atrophy

Interventions

bimagrumab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Thinness; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

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: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: August 20, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 3, 2016
• Results First Posted: May 3, 2016

Record last verified: 2016-04

Locations

US (5); NL (1); GB (3)