A Clinical Study to Determine the Safety, Tolerability and Effect of RLS-0071 Doses When Given to Healthy Adults After Inhaling LPS

NCT05351671 | Completed Phase 1 FDA Drug

• 2 other identifiers: RLS-0071-1032021-006288-26
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in absolute neutrophil count in induced sputum

  Primary PD

  At 6 and 24 hours after inhaled lipopolysaccharide (LPS).

Secondary Outcomes (1)

• Change from Baseline in cytokines (Th1 and Th17) in induced sputum

  At 6 and 24 hours after inhaled LPS.

Other Outcomes (17)

• Change from Baseline in MPO level in sputum

  At 6 and 24 hours after inhaled LPS.

• Change from Baseline in concentration of myeloperoxidase (MPO) binding in blood

  At 6 and 24 hours after inhaled LPS.

• Change from Baseline in amount of cell-free DNA in blood.

  At 6 and 24 hours after inhaled LPS.

Study Arms (3)

Arm A

EXPERIMENTAL

RLS-0071 lower dose group

Drug: RLS-0071 (10 mg/kg intravenously every 8 hours for total of 3 doses)

Arm B

EXPERIMENTAL

RLS-0071 higher dose group

Drug: RLS-0071 (loading dose of 120 mg/kg followed by 40 mg/kg every 8 hours for 2 additional doses)

Arm C

PLACEBO COMPARATOR

Placebo group

Drug: Placebo (saline dosed every 8 hours for a total of 3 doses)

Interventions

RLS-0071 (10 mg/kg intravenously every 8 hours for total of 3 doses) DRUG

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.

Arm A

RLS-0071 (loading dose of 120 mg/kg followed by 40 mg/kg every 8 hours for 2 additional doses) DRUG

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.

Arm B

Placebo (saline dosed every 8 hours for a total of 3 doses) DRUG

After challenge with inhaled LPS, subjects will receive IV infusion of placebo (saline) dosed every 8 hours for a total of 3 doses.

Arm C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 55 years, inclusive, at the time of Screening
• Female subjects of childbearing potential must agree to use a highly effective contraceptive method from Screening until 30 days after the last investigational medicinal product (IMP) intake and have a negative pregnancy test at Screening (blood test). The following contraceptive measures can achieve a failure rate of less than 1% per year when used consistently and correctly and are considered highly effective measures:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral / intravaginal / transdermal)
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral / injectable / implantable)
• intrauterine device
• intrauterine hormone-releasing system
• bilateral tubal occlusion
• vasectomized partner (provided that the partner is the sole sexual partner of the woman of childbearing potential and has received medical assessment of the surgical success)
• sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment). Abstinence is only accepted as true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods and withdrawal\] is not an acceptable method of contraception).
• Female subjects who are not of childbearing potential are exempt from contraceptive requirements. To be considered of non-childbearing potential female subjects must meet the following requirements: Must be permanently sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before first dosing with the investigational medicinal product) or postmenopausal (defined as no menses for 12 months without an alternative medical cause).
• A male study subject must agree to use a double barrier method (eg, condom and spermicide) during sexual contact with a pregnant woman or a woman of childbearing potential ,and agree to not donate sperm during the study and for at least 90 days after the last dose of the IMP
• Medically healthy on the basis of medical history, physical examination, and clinical laboratory testing in the opinion of the Investigator
• Nonsmokers and nonusers of nicotine-containing products, including vaping devices for at least 6 continuous months before the first dosing with the investigational medicinal product and for the duration of the study, to be confirmed by cotinine testing at Screening and a smoking history of \< 5 pack years
• Negative alcohol testing at Screening and Day 1
• Negative cotinine and drug screen testing at Screening.

You may not qualify if:

• Use of any prescription or over-the-counter (OTC) medications, herbal products (eg, cannabidiol, St John's Wort, milk thistle), or supplements/vitamins within 14 days or 5 half-lives (whichever is longer) before first dosing with IMP and for the duration of the study, with the exception of those approved by the Investigator and Sponsor (eg, oral contraceptives, hormone replacement therapy, acetaminophen for pain relief).
• Receipt of any investigational agent or treatment within 30 days or 5 half-lives, whichever is longer, before first dosing with IMP, or concurrent participation in another clinical study.
• Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months before first dosing with IMP.
• Note: Influenza and COVID-19 vaccines will be allowed if all doses in the regimen have been administered more than 21 days before first dosing with IMP.
• History of any major surgery within 6 months before first dosing with IMP.
• Prior diagnosis of COVID 19 within 90 days before first dosing with IMP.
• History of hepatic disease, or current clinically significant liver function test results, defined as ALT, AST, total bilirubin and fractionated bilirubin, or alkaline phosphatase \> 1.5 × upper limit of normal (ULN) at Screening.
• Note: Isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated, and direct bilirubin is \< 35%.
• History of any clinically relevant or chronic psychiatric, renal, hepatic, pancreatic, cardiovascular, neurological, hematological, or gastrointestinal abnormality (eg, inflammatory bowel disease)
• History of severe allergic/anaphylactic reaction
• History of autoimmune disease including glomerulonephritis
• Known hypersensitivity to the active substance or to any of the excipients of each IMP including lipopolysaccharide (LPS) and polyethylene glycol (PEG)
• History of any active infection within 14 days before dosing with IMP, if deemed clinically significant by the Investigator and Sponsor
• Any acute illness within 30 days before dosing with IMP
• Lower respiratory tract infection within 3 months before first dosing with IMP

Sponsors & Collaborators

• ReAlta Life Sciences, Inc.: lead
• FGK Clinical Research GmbH: collaborator

Study Sites (1)

Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)

Hanover, 30625, Germany

Location

MeSH Terms

Interventions

RLS-0071

Study Officials

• Kenji Cunnion, MD, MPH

  ReAlta Life Sciences, Inc.

  STUDY CHAIR

• Linda Dell

  ReAlta Life Sciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the entire study, subjects, Investigators, the Sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 28, 2022
• Study Start: May 23, 2022
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: March 31, 2023

Record last verified: 2023-03

Locations

DE (1)