A Phase 1 SAD/MAD Study of RLS-0071 in Healthy Volunteers in Support of a COVID-19 Development Program

NCT05298787 | Completed Phase 1 FDA Drug

• 1 other identifier: RLS-0071-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  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).

  From initiation of study treatment (Day 1) through follow-up period (Day 30)

• Incidence of abnormal laboratory test results

  From initiation of study treatment (Day 1) through follow-up period (Day 30)

Secondary Outcomes (6)

• Plasma maximum measured drug concentration (Cmax)

  0 - 1 week

• Time of maximum concentration (Tmax)

  0 - 1 week

• Area under the concentration-time curve (AUC)

  0 - 1 week

• Terminal elimination half-life (T 1/2)

  0 - 1 week

• Pharmacodynamic parameter - mCH50 assay

  0 - 1 week

Other Outcomes (2)

• Exploratory Biomarker - Membrane-attack complex assay (sC5b-9)

  0 - 1 week

• Immunogenicity characteristics - presence of anti-RLS-0071 antibody (ADA)

  From initiation of study treatment (Day 1) through follow-up period (Day 30)

Study Arms (7)

SAD - 2mg/kg or placebo IV infusion

EXPERIMENTAL

Single IV infusion

Drug: RLS-0071; Drug: Saline Placebo

SAD - 10mg/kg or placebo IV infusion

EXPERIMENTAL

Single IV infusion

Drug: RLS-0071; Drug: Saline Placebo

SAD - 40mg/kg or placebo IV infusion

EXPERIMENTAL

Single IV infusion

Drug: RLS-0071; Drug: Saline Placebo

MAD - 2mg/kg or placebo IV infusion

EXPERIMENTAL

IV infusion given every 8 hours over 3 days for a total of 9 doses

Drug: RLS-0071; Drug: Saline Placebo

MAD - 10mg/kg or placebo IV infusion

EXPERIMENTAL

IV infusion given every 8 hours over 3 days for a total of 9 doses

Drug: RLS-0071; Drug: Saline Placebo

SAD - 120mg/kg or placebo IV infusion

EXPERIMENTAL

Single IV infusion

Drug: RLS-0071; Drug: Saline Placebo

MAD - 40mg/kg or placebo IV infusion

EXPERIMENTAL

IV infusion given every 8 hours over 3 days for a total of 9 doses

Drug: RLS-0071; Drug: Saline Placebo

Interventions

RLS-0071 DRUG

RLS-0071 is administered as an IV infusion

MAD - 10mg/kg or placebo IV infusion; MAD - 2mg/kg or placebo IV infusion; MAD - 40mg/kg or placebo IV infusion; SAD - 10mg/kg or placebo IV infusion; SAD - 120mg/kg or placebo IV infusion; SAD - 2mg/kg or placebo IV infusion; SAD - 40mg/kg or placebo IV infusion

Saline Placebo DRUG

Placebo is administered as an IV infusion

MAD - 10mg/kg or placebo IV infusion; MAD - 2mg/kg or placebo IV infusion; MAD - 40mg/kg or placebo IV infusion; SAD - 10mg/kg or placebo IV infusion; SAD - 120mg/kg or placebo IV infusion; SAD - 2mg/kg or placebo IV infusion; SAD - 40mg/kg or placebo IV infusion

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Heart rate (HR), \> 45 to ≤ 100 bpm
• Weight ≤ 90 kg and body mass index (BMI) ≥ 18 and ≤ 30 kg/m2 at Screening.
• Normal renal function, defined as estimated creatinine clearance (CrCl) \> 90 mL/min (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula) at Screening; an Investigator can determine based on clinical judgment whether a lower clearance rate can be accepted based on the muscle composition of the subject.
• Willing and able to provide voluntary, written informed consent to participate in the study.
• Able to communicate well with the Investigator and/or study site personnel and to comply with the requirements of the entire study.

You may not qualify if:

• 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.
• Subjects with a history of autoimmune disease, glomerulonephritis, or vasculitis.
• Known history of allergy to any component of study intervention including polyethylene glycol (PEG).
• History of any active infection within 14 days dosing with study intervention, if deemed clinically significant by the Investigator and Sponsor.
• Any acute illness within 30 days before dosing with study intervention.
• History of warfarin use or International Normalized Ratio (INR) ≥ 1.5.

Sponsors & Collaborators

• ReAlta Life Sciences, Inc.: lead

Study Sites (1)

Altasciences

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

RLS-0071

Study Officials

• Kenji Cunnion, MD

  Chief Medical Officer, 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
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each cohort will include 8 subjects randomized to receive either RLS-0071 (6 subjects) or placebo (2 subjects). Up to 7 cohorts (4 single-ascending dose \[SAD\] and 3 multiple-ascending dose \[MAD\]) enrolling up to 56 subjects are planned for the study. Subjects enrolled in a SAD cohort will receive a single infusion of RLS-0071. Subjects enrolled in a MAD cohort will receive a RLS-0071 infusion every (q) 8 hours for a total of 9 doses, with the ninth infusion occurring in the morning on Day 4. Dose escalation will depend on the Safety Review Committee (SRC) review of available blinded safety and PK data through the observation period of the previous cohort (ie, 48 hours after the last dose of study intervention).

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 28, 2022
• Study Start: January 13, 2021
• Primary Completion: August 16, 2021
• Study Completion: August 16, 2021
• Last Updated: March 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)