Secondary Outcomes
Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.
Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).
Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.
Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).
Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose apparent total body clearance for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.
Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.
Time: Through study completion at Day 28 following last dose.
Measure: Overall survival.
Time: Through Day 15 and through study completion at Day 28 following last dose.
Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.
Time: Days on ventilation while in the hospital through study completion at Day 28.
Measure: Incidence of transfer to the ICU.
Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.
Measure: Duration of hospitalization after treatment (days).
Time: Through study completion at Day 28 following last dose.
Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).
Time: Through study completion at Day 28 following last dose.
Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.
Time: Through study completion at Day 28 following last dose.
Measure: Duration of requirement for supplemental oxygen after treatment (days).
Time: Through study completion at Day 28 following last dose.
Measure: PaO2/FiO2
Time: Through study completion at Day 28 following last dose.
Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.
Time: Through Day 15 and through study completion at Day 28 following last dose.
Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.
Time: Through Day 15 and through study completion at Day 28 following last dose.
Description: Dialysis will be assessed by the investigator with CTCAE's latest version.
Measure: Incidence and duration after treatment (days) of dialysis.
Time: Through Day 15 and through study completion at Day 28 following last dose.
Measure: Levels of complement activity (eg, CH50).
Time: Through study completion at Day 28 following last dose.
Measure: Levels of C1q (free and bound to RLS-0071).
Time: Through study completion at Day 28 following last dose.
