A Clinical Study to Determine the Safety, Tolerability and Effect of RLS-0071 Doses When Given to Healthy Adults After Inhaling LPS
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1b, randomized, double-blind, placebo-controlled, dose range finding study to
      assess the safety, tolerability, pharmacodynamics (PK) and pharmacokinetics (PD) of RLS-0071
      in healthy adult subjects after challenge with inhaled lipopolysaccharide (LPS).

      Clinical data are required to determine the potential benefit of RLS-0071, a novel drug that
      specifically inhibits multiple inflammatory pathways, for the treatment of severe asthma.
      This study has been designed to evaluate the efficacy of IV administered RLS-0071 to reduce
      inflammation symptoms in healthy subjects challenged with inhaled LPS, a well-known agent
      that produces a safe and well-controlled inflammatory response in the lung. This is a
      critical proof-of-concept study and dose-optimization study for future studies in severe
      asthma patients.

      A total of 48 healthy adult subjects are planned to be enrolled in this study. Subjects will
      be randomly allocated to either of the treatment arms (Arm A or Arm B) with RLS-0071 or the
      placebo arm (Arm C) in a 1:1:1 ratio. Subjects will either receive intravenous infusion of
      RLS-0071 at a lower dose every 8 hours for a total of 3 doses (Arm A), RLS-0071 at a higher
      dose every 8 hours for a total of 3 doses (Arm B) or placebo dosed every 8 hours for a total
      of 3 doses (Arm C). Each subject completing the study will be evaluated for up to a total of
      7 days. Subjects will be permitted to participate in only 1 arm of the study. Subjects
      discontinuing the study before data was collected at 6 hours post LPS challenge will be
      considered dropouts and will be replaced.
    

Detailed description: 
      The inclusion of a double-blind design allows a comparison between subjects receiving
      RLS-0071 and placebo subjects who are experiencing the same procedures and restrictions in an
      unbiased manner. The inclusion of a placebo control group will facilitate the distinction
      between efficacy signals and possible procedural/environmental events.

      Eligibility criteria have been included to mitigate the risk to study subjects. Vulnerable
      populations such as children are excluded, as well as subjects whose medical history suggest
      a higher risk of experiencing adverse effects.

      LPS inhalation is used in this study to be able to evaluate proof-of-concept efficacy of
      RLS-0071 in otherwise healthy subjects. Thus, PD assessments will be conducted to provide
      evidence of target engagement and guide the design of future severe asthma studies.
    

Intervention name(s): RLS-0071 (10 mg/kg intravenously every 8 hours for total of 3 doses); RLS-0071 (loading dose of 120 mg/kg followed by 40 mg/kg every 8 hours for 2 additional doses); Placebo (saline dosed every 8 hours for a total of 3 doses)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): After challenge with inhaled LPS, subjects will receive IV infusion of RLS-0071 at 10 mg/kg every 8 hours for total of 3 doses.; After challenge with inhaled LPS, subjects will receive IV infusion of RLS-0071 at a loading dose of 120 mg/kg followed by 40 mg/kg every 8 hours for 2 additional doses.; After challenge with inhaled LPS, subjects will receive IV infusion of placebo (saline) dosed every 8 hours for a total of 3 doses.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomly allocated to either of the treatment arms with RLS-0071 or the placebo arm in a 1:1:1 ratio. Subjects will be permitted to participate in only 1 arm of the study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment