Safety, PK and PD Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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AECOPD is a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity, and quality of life (QoL). RLS-0071 is a novel peptide being developed for the treatment of AECOPD. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of adults with moderate exacerbations of COPD.

Detailed Description
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This is a randomized, double-blind, placebo controlled trial in hospitalized participants with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) to evaluate the safety, tolerability, preliminary efficacy, PK, and PD of RLS-0071 compared to Placebo in the treatment of AECOPD. The dosing regimen will be 3 times a day for at least 3 days and up to 5 days total if still hospitalized. Participants will be followed for efficacy and safety for 30 and 60 days after the final dose. RLS-0071 or Placebo will be given as add-on therapy to SOC management for acute exacerbations of COPD.

Official Title
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A Phase 2a Randomized, Doubled-Blind, Placebo-Controlled Trial to Evaluate Safety, Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Conditions
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Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: RLS-0071
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized participants with a prior diagnosis of COPD including spirometry within the prior year documenting a postbronchodilator FEV1/FVC ≤ 0.7 and an FEV1 ≤ 80%, and a clinician identified admitting diagnosis of AECOPD: acute increase in dyspnea, sputum volume or purulence - without other attributable cause. Participants must have a moderate exacerbation of COPD according to the Rome guidelines ≥ 10 pack-years smoking history. Exclusion Criteria: Endotracheal intubation or mechanical ventilation. Participants with severe exacerbation of COPD according to the Rome guidelines Participants with signs and symptoms consistent with an alternative diagnosis for worsening of pulmonary status Interstitial lung disease. Current or prior history of asthma. Known hypersensitivity, allergy, or reaction to polyethylene glycol (PEG) Preexisting autoimmune disease: History of autoimmune disease and/or use of chronic steroids of >10mg/d (prednisone or equivalent) for more than 14 days prior to enrollment Current renal dialysis or renal dialysis planned or anticipated in the next 7 days. Has confounding medical conditions, including: diabetic coma, uncontrolled New York Heart Association Class IV congestive heart failure, uncontrolled angina, stroke or transient ischemic attack (TIA) within 4 weeks before study entry, clinically significant arrhythmias not controlled by medication, or idiopathic pulmonary fibrosis, Has a weight >120 kg at Screening. Known pregnancy, a positive pregnancy test at screening, or lactation for WOCBP. Has systemic immunosuppression/immune deficiency

Ages Eligible for Study
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Minimum Age: 30 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RLS-0071<br>Doses of RLS-0071, will be administered Q8H, three times a day, for at least 3 days and up to 5 days | Drug: RLS-0071<br>* RLS-0071, will be administered as an IV infusion 10 mg/kg. Planned infusion duration is 8 minutes.<br>|
| Placebo Comparator: Placebo<br>Doses of Placebo for RLS-0071, will be administered Q8H, three times a day, for at least 3 days and up to 5 days | Drug: Placebo<br>* Placebo control (commercial sterile saline), will be administered as an IV infusion. Planned infusion duration is 8 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |  | Day 1 to Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure respiratory rate by measuring breaths per minute daily |  | Day 1 - Up to Day 5 | 
| Measure the % O2 saturation via pulse oximetry daily |  | Day 1 - Up to Day 5 | 
| Time to reach maximum observed serum concentration (Tmax) for RLS-0071 |  | Day 1 and Day 3 | 
| Maximum Observed Serum Concentration (Cmax) for RLS-0071 |  | Day 1 and Day 3 | 
| Area Under the Curve From Time 0 to Infinity (AUC [0 - infinity]) for RLS-0071 |  | Day 1 and Day 3 | 
| Terminal Phase Elimination Half-Life (t1/2) for RLS-0071 |  | Day 1 and Day 3 | 
| Evaluate the change in plasma neutrophil counts from Day 0 up to Day 5. |  | Day 0 up to Day 5. | 
| Evaluate the change from baseline in eosinophil counts from Day 0 up to Day 5. |  | Day 0 up to Day 5. | 
| Evaluate the change from baseline in erythrocyte sedimentation rate from Day 0 up to Day 5. |  | Day 0 up to Day 5. | 
| Evaluate the change in baseline in c-reactive protein in blood from Day 0 up to Day 5. |  | Day 0 up to Day 5. | 
| Number of days participant was hospitalized (length of stay). |  | Day 1 - Day 60 | 
| Number of participants rehospitalized for COPD up to Day 60 |  | Day 1 to Day 60 | 
| Number of participants that progressed to mechanical ventilation |  | Day 1 - Day 5 | 
| Mortality rate of participants at 60 days after discharge |  | Day 1 to Day 60 | 
| Measure heart rate via beats per minute daily |  | Day 1 - Up to Day 5 |