SUN11031 in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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To evaluate SUN11031 for subcutaneous injection compared to placebo in subjects with cachexia associated with Chronic Obstructive Pulmonary Disease (COPD) to determine the effect on physical performance and body composition.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SUN11031 for Injection Administered Subcutaneously Twice Daily for 12 Weeks to Subjects Having Cachexia Associated With Chronic Obstructive Pulmonary Disease

Conditions
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Cachexia

Intervention / Treatment
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* Drug: Placebo comparator
* Drug: SUN11031 20 μg/kg
* Drug: SUN11031 40 μg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each participant had to meet the following criteria to be enrolled in the study: Male or non-pregnant female participants 50 years or older with a clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) for greater than or equal to 12 months Walked a distance of greater than or equal to 100 but less than or equal to 450 meters during the 6-Minute Walk Test (MWT) performed at screening. Chest x-ray within the past year that was compatible with COPD Documented involuntary nonedematous weight loss of greater than 5% of participant's usual body weight over the past 12 months or BMI less than or equal to 21 kg/m^2 for males or Body Mass Index (BMI) less than or equal to 20 kg/m^2 for females Female participants who were clinically sterile (eg, either postmenopausal or had undergone a tubal ligation or hysterectomy) or were practicing a medically acceptable method of birth control (eg, oral, transdermal, implantable, or injectable contraceptive medications; double-barrier method or intrauterine device) Exclusion Criteria: Participants who met any of the following criteria were excluded from the study: BMI greater than 26 kg/m^2 Used, over a total of 7 or more days, parenteral corticosteroids at a dose equivalent to prednisone at greater than or equal to 5 mg/day or oral corticosteroids at a dose equivalent to prednisone at greater than 10 mg/day within the 2 months before screening; however, participants were allowed to participate if on stable doses equivalent to prednisone at less than or equal to 10 mg/day for at least 2 months before screening, and were planning to remain on the same stable dose throughout the study Were planning to start a pulmonary rehabilitation program during the study (participant may have been enrolled in the study if he or she was currently on a stable maintenance program) Weight loss that was considered to be, in the opinion of the investigator, the result of food deprivation Unintended weight loss that may have been due to disease other than COPD Unable or unwilling to be trained to self-administer the study drug by subcutaneous injection bid, and for whom arrangements could not be made for a third party to reliably administer the injections Severe anemia (hemoglobin less than or equal to 8 g/dL) COPD exacerbation defined as a Type 1 or 2 exacerbation according to the Winnipeg criteria, acute infection, or prolonged fever within 4 weeks before screening Undergoing treatment or evaluation for cancer, or had a history of treatment for cancer within the past 3 years, exception being nonmelanoma skin cancer (basal cell or squamous cell carcinoma of the skin) and carcinoma in situ of the cervix Type I or type II diabetes mellitus or a fasting serum glucose of greater than or equal to 115 mg/dL (6.4 mmol/L) (fasting was overnight) Serious disease or conditions that would have interfered with the participant's ability to complete the functional measures included in this protocol; or any illness that, in the opinion of the investigator, might have interfered with the results of the study or the participant's ability to participate Pulmonary embolism, deep venous thrombosis, or clinically significant primary pulmonary hypertension within the past 6 months Significant ischemic heart disease or chronic heart failure (New York Heart Association Class IV cardiac disease) Uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 110 mm Hg) A history of symptomatic orthostatic hypotension or syncope; or orthostatic hypotension at screening or baseline (Days -6 to -3) (orthostatic hypotension was defined as a decrease in systolic blood pressure by greater than or equal to 20 mm Hg measured after 2 minutes in a standing position compared with the systolic blood pressure measured after 10 minutes in a supine position) Evidence of ascites, pleural effusion, or lower extremity edema Severe vitamin D deficiency (25-hydroxyvitamin D less than 10 ng/mL) Known mechanical obstruction of the alimentary tract and/or malabsorption Dental or swallowing problems that may have had a negative effect on food intake Serum creatinine greater than 2.5 mg/dL; or alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase greater than 3 times the upper limit of normal, or bilirubin greater than 2.5 mg/dL A diagnosis of human immunodeficiency virus infection or AIDS Used any prescription drugs and non-prescription drugs/herbs that cause weight loss or affect appetite and absorption or that may cause nausea; or used appetite-promoting or anabolic medications within 15 days before screening A history of alcohol or drug abuse that, in the opinion of the investigator, would have interfered with the participant's ability to comply with the dosing schedule and protocol-specified requirements Hypersensitive to any component of SUN11031, or participated at any time in any study in which SUN11031 was administered Received an investigational drug or product, or participated in a drug study within 30 days before screening Non-ambulatory or unwilling to cooperate fully with the investigator or a designee, or unwilling or unable to comply with study requirements, such as all assessments required by the protocol, including completion of measures for functional capacity and pulmonary function, or frequent blood sampling and meal instructions; or unable or unwilling to attend all study visits

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>SUN11031 for injection, low dose, twice daily for 12 weeks | Drug: SUN11031 20 μg/kg<br>* Twice daily subcutaneous injections of SUN11031 20 μg/kg for 12 weeks.<br>|
| Experimental: Group 2<br>SUN11031 for injection, higher dose, twice daily for 12 weeks | Drug: SUN11031 40 μg/kg<br>* Twice daily subcutaneous injections of SUN11031 40 μg/kg for 12 weeks.<br>|
| Placebo Comparator: Group 3<br>Placebo injection, twice daily for 12 weeks | Drug: Placebo comparator<br>* Twice daily subcutaneous injections of placebo for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Day 85 in the Distance Walked During the 6 Minute Walk Test (MWT) Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD) | Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites. | Baseline up to Day 85 post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Days 29, 57, and 85 in the Distance Walked During the 6 Minute Walk Test (MWT) Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD) | Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites. | Baseline up to Day 29, Day 57, and Day 85 post dose. | 
| Mean Change From Baseline to Days 29, 57, and 85 in the Distance Walked During the 6 Minute Walk Test (MWT) By Sub-groups Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD) | Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites. | Baseline up to Day 29, Day 57, and Day 85 post dose. | 
| Number of Participants With Improvement in Distance Walked During the 6 Minute Walk Test (MWT) By Sub-groups Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites. | Baseline up to Day 85 post dose. | 
| Mean Change in Body Weight From Baseline Through Day 99 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Measurements of body weight were performed in the morning when the participant had an empty stomach (ie, had consumed no food overnight) and had emptied the bladder and had a bowel movement, if possible. These measurements were performed using the same calibrated scale for an individual participant throughout study. | Baseline up to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85, and Day 99 post dose. | 
| Mean Change in Lean Body Mass From Baseline Through Days 29, 85 and 99 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Lean body mass was assessed based on whole-body dual-energy x-ray absorptiometry (DXA). | Baseline up to Day 29, Day 85, and Day 99 post dose. | 
| Absolute Concentrations of SUN11031 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Absolute concentrations of SUN11031 in participant plasma samples were measured. When participants were randomly assigned into 1 of 3 treatment groups at baseline, they were also randomly assigned into 1 of 2 sequences in the pharmacokinetic (PK) sparse sampling schedule based on the randomization number. | Day 1 and Day 85 pre-dose; Day 1 at 1 hour and 4 hours; Day 29 at 0.08 hours and 1.5 hours; Day 57 at 0.08 hours and 6 hours; Day 85 at 0.5 hours and 3 hours postdose. | 
| Absolute Concentrations of SUN11031 Metabolites Desacyl-ghrelin Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Absolute concentrations of SUN11031 metabolites desacyl-ghrelin in participant plasma samples were measured. When participants were randomly assigned into 1 of 3 treatment groups at baseline, they were also randomly assigned into 1 of 2 sequences in the pharmacokinetic (PK) sparse sampling schedule based on the randomization number. | Day 1 and Day 85 pre-dose; Day 1 at 1 hour and 4 hours; Day 29 at 0.08 hours and 1.5 hours; Day 57 at 0.08 hours and 6 hours; Day 85 at 0.5 hours and 3 hours postdose. | 
| Treatment Emergent Adverse Events Reported in ≥ 2% of Participants Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease | Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that occurred from the time treatment was administered at Day 1 through the last follow-up visit or a worsening of a pre-existing condition. | Baseline up to Day 113 post dose, up to a total of 134 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cachexia, COPD, Chronic Obstructive Pulmonary Disease