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

A Randomized, Double Blind, Placebo Controlled, Multi-centre Study to Asses the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of BYM338 in Chronic Obstructive Pulmonary Disease Patients With Cachexia

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD) With Cachexia
• Intervention / Treatment: Drug: Placebo; Drug: BYM338

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6211
    • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SW 6NP
    • Novartis Investigative Site
  • Machester, United Kingdom, M23 9QZ
    • Novartis Investigative Site
• United States
  • California
    • Torrance, California, United States, 90502
      • Novartis Investigative Site
  • Georgia
    • Savannah, Georgia, United States, 31419
      • Novartis Investigative Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • Novartis Investigative Site
  • Montana
    • Missoula, Montana, United States, 59808
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• 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.

Exclusion criteria:

• 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.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BYM338	Drug: BYM338; BYM338

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6 Minute Walk Distance Compared to Placebo	Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)	Baseline, Weeks 4, 8, 16, 24
Maximum Observed Serum Concentration (Cmax)	The observed maximum plasma concentration following drug administration	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)	The time to reach the maximum concentration after drug administration	24 weeks
AUC0-56 and AUClast	AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.	0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 1, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (Estimate): August 20, 2012

Study Record Updates

• Last Update Posted (Estimate): May 3, 2016
• Last Update Submitted That Met QC Criteria: April 27, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease; COPD; cachexia; muscle wasting
• Additional Relevant MeSH Terms: Metabolic Diseases; Respiratory Tract Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Emaciation; Weight Loss; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Wasting Syndrome; Cachexia
• Other Study ID Numbers: CBYM338X2204; 2011-000461-12