A Phase 1, Randomized, Double-Blind, Placebo-Controlled, SAD/MAD Adaptive-Design Study to Assess the Safety, Tolerability, PK, and PD of RLS-0071 in Healthy Adult Subjects in Support of a COVID-19 Development Program
Overview
- Phase
- Phase 1
- Intervention
- RLS-0071
- Conditions
- Healthy Volunteer
- Sponsor
- ReAlta Life Sciences, Inc.
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Incidence of abnormal laboratory test results
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase 1, single-center, randomized, double-blind, placebo-controlled, adaptive-design study to assess the safety, tolerability, PK, and PD of single- and multiple-ascending doses of RLS-0071 in healthy adult subjects.
Detailed Description
The present study is a single-ascending dose (SAD) and multiple-ascending dose (MAD) evaluation of RLS-0071 in healthy volunteers. This study is designed to evaluate the safety and tolerability of RLS-0071 administered by the intravenous (IV) route to healthy subjects as single- and multiple-ascending doses. Importantly, a SAD/MAD study in healthy subjects is critical to generate robust pharmacokinetic (PK) data using intensified PK sample collection, not feasible in a patient study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 60 years, inclusive, at the time of Screening.
- •A female study subject must meet one of the following criteria: If of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study intervention, during the study, and for at least 30 days after the last dose of the study intervention.
- •a. An acceptable method of contraception includes one of the following: i. Abstinence from heterosexual intercourse ii. Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch) iii. Intrauterine device (with or without hormones) -OR- b. Agrees to use a double barrier method (eg, condom and spermicide) during the study and for at least 30 days after the last dose of the study intervention Female subjects who are not of childbearing potential are exempt from contraceptive requirements. To be considered of nonchildbearing potential female subjects must meet the following requirements: Must be surgically sterile (documented hysterectomy, tubal ligation, or bilateral salpingo-oophorectomy at least 3 months prior to Day 1) or postmenopausal (defined as 12 months from the time of last spontaneous menses). If necessary, a follicle-stimulating hormone (FSH) level \> 35 IU/L at Screening will be considered confirmatory in the absence of a clear postmenopausal history.
- •A male study subject who engages in sexual activity that has the risk of pregnancy must agree to use a double barrier method (eg, condom and spermicide) and agree to not donate sperm during the study and for at least 90 days after the last dose of the study intervention.
- •Medically healthy on the basis of medical history, physical examination, and clinical laboratory testing in the opinion of the Investigator or designee.
- •Nonsmokers and nonusers of nicotine-containing products, including e-cigarettes, for at least 6 continuous months before the first dose of study intervention and for the duration of the study, to be confirmed by cotinine testing at Screening.
- •Negative drug/alcohol testing at Screening and Check-in (Day -1).
- •Vital signs (after semirecumbent for at least 5 minutes) that are within the following ranges at Screening and Check-in (Day -1):
- •Systolic blood pressure (BP), 90 to 140 mmHg, inclusive
- •Diastolic BP, 50 to 90 mmHg, inclusive
Exclusion Criteria
- •Use of any prescription or over-the-counter (OTC) medications, herbal products (eg, St John's Wort, milk thistle), or supplements/vitamins within 14 days before dosing with study intervention and for the duration of the study, with the exception of those approved by the Investigator and Sponsor (eg, oral contraceptives, hormone replacement therapy).
- •Receipt of any investigational agent or treatment within 30 days or 5 half-lives, whichever is longer, prior to Screening.
- •Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months before dosing with study intervention.
- •Note: Influenza and COVID-19 vaccine will be allowed if all doses in the regimen have been administered more than 21 days before dosing with study intervention.
- •History of any major surgery within 6 months before dosing with study intervention.
- •History of hepatic disease, or current clinically significant liver function test results, defined as alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin and fractionated bilirubin, and alkaline phosphatase (AP) \> 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.
- •Diagnosis or positive Screening test for antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (DNA) antibodies (anti-dsDNA), anti-ribonucleoprotein antibodies (anti-RNP), anti-Sjögren's syndrome type A antibodies (anti-Ro/SSA), anti-Sjögren's syndrome type B antibodies (anti-La/SSB), anti-Smith antibodies (anti-SM), and anti-phospholipid antibodies.
Arms & Interventions
SAD - 120mg/kg or placebo IV infusion
Single IV infusion
Intervention: RLS-0071
SAD - 120mg/kg or placebo IV infusion
Single IV infusion
Intervention: Saline Placebo
SAD - 2mg/kg or placebo IV infusion
Single IV infusion
Intervention: RLS-0071
SAD - 2mg/kg or placebo IV infusion
Single IV infusion
Intervention: Saline Placebo
SAD - 10mg/kg or placebo IV infusion
Single IV infusion
Intervention: RLS-0071
SAD - 10mg/kg or placebo IV infusion
Single IV infusion
Intervention: Saline Placebo
SAD - 40mg/kg or placebo IV infusion
Single IV infusion
Intervention: RLS-0071
SAD - 40mg/kg or placebo IV infusion
Single IV infusion
Intervention: Saline Placebo
MAD - 2mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: RLS-0071
MAD - 2mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: Saline Placebo
MAD - 10mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: RLS-0071
MAD - 10mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: Saline Placebo
MAD - 40mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: RLS-0071
MAD - 40mg/kg or placebo IV infusion
IV infusion given every 8 hours over 3 days for a total of 9 doses
Intervention: Saline Placebo
Outcomes
Primary Outcomes
Incidence of abnormal laboratory test results
Time Frame: From initiation of study treatment (Day 1) through follow-up period (Day 30)
Incidence of adverse events
Time Frame: From initiation of study treatment (Day 1) through follow-up period (Day 30)
Safety and tolerability will be assessed throughout the study by monitoring and evaluating TEAEs, including any complications resulting from the IV infusion. All AEs will be collected from the start of study intervention administration through Day 30 or Early Termination (ET). Adverse event grading will be defined by the CTCAE (latest version).
Secondary Outcomes
- Plasma maximum measured drug concentration (Cmax)(0 - 1 week)
- Pharmacodynamic parameter - C1q levels(0 - 1 week)
- Terminal elimination half-life (T 1/2)(0 - 1 week)
- Pharmacodynamic parameter - mCH50 assay(0 - 1 week)
- Time of maximum concentration (Tmax)(0 - 1 week)
- Area under the concentration-time curve (AUC)(0 - 1 week)