Clinical trial NCT01669174: BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD) With Cachexia
Keywords: Chronic Obstructive Pulmonary Disease
COPD; cachexia; muscle wasting
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-08-20
Enrollment: 67
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
timeFrame: Baseline, Weeks 4, 8, 16, 24
Secondary outcomes:
measure: Change in 6 Minute Walk Distance Compared to Placebo
timeFrame: Baseline, Weeks 4, 8, 16, 24
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
timeFrame: 24 weeks
measure: AUC0-56 and AUClast
timeFrame: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Novartis Investigative Site
state: California
city: Savannah
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Normal
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Missoula
country: United States
facility: Novartis Investigative Site
state: Montana
city: Spartanburg
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Machester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.