Safety, Tolerability, and Pharmacokinetics of ARCT-032 in Healthy Adult Subjects and Adults With Cystic Fibrosis.

A Study in Two Parts: (Phase 1) A Randomized, Double-blinded, Placebo--controlled, Single-ascending-dose Study in Healthy Adult Subjects and (Phase 1b) an Open-label, Nested, Divided-dose Study in Adults With Cystic Fibrosis to Assess the Safety, Tolerability, and Pharmacokinetics of ARCT-032

Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-032 in healthy adult subjects (Phase 1) and of two doses in Adults with Cystic Fibrosis (Phase 1b).

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Placebo; Drug: ARCT-032

Detailed Description

Phase 1 of this study is a single ascending dose, first-in-human study to determine the safety, tolerability, and pharmacokinetics (PK) of ARCT-032. After screening, healthy adult participants will be randomized 3:1 to inhale a single dose of nebulized ARCT-032 or placebo. There are 4 planned sequential dose cohorts. After dosing, participants will have follow-up assessments over a 4-week period.

Phase 1b in adults with cystic fibrosis will enroll after Phase 1 is completed and safety data are reviewed. Phase 1b is an open-label, two-dose study in adults with cystic fibrosis to assess the safety, tolerability, and pharmacokinetics of ARCT-032. After completion of screening, each participants will inhale two doses of nebulized ARCT-032 two days apart. Participants will have follow-up assessments over a 4-week period.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure Manager; Phone Number: (858) 900-2660; Email: clinicaltrials@arcturusrx.com

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Clinical Research
    • Principal Investigator: Christian Schwabe, MD
    • Contact: Olivia Dempster; Email: arctic@nzcr.co.nz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Phase 1: Healthy males or females aged 18 to 65 years at the time of informed consent.

   Phase 1b: Males or females aged 18 to 65 years with confirmed diagnosis of CF documented in subject's medical record

2. Body weight between 40-100Kg and body mass index between 16-35 kg/m2

3. Phase 1: Forced expiratory volume (FEV1) at screening >85% of predicted value for age, sex, and height.

   Phase 1b: FEV1 at screening between 50% and 100% of predicted value

4. Surgically sterile or using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days after the last dose of study drug.
5. Phase 1b only: Subjects with CF on CFTR modulator therapy must be on a stable regimen for at least 2 months prior to screening.

Key Exclusion Criteria:

1. History of illness or condition that might pose an additional risk or may confound study results.
2. Pregnant or lactating (breast feeding)
3. History of severe allergic reaction to a liposomal product
4. Clinically significant abnormalities in Screening laboratory results
5. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
6. Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug, whichever is longer
7. Drug or alcohol abuse within the past year
8. History of moderate to heavy smoking or vaping (>10 cigarettes/sessions per day) within 6 months prior to the dose of study drug. Participants must be willing to refrain from smoking or vaping within 1 week of dosing through Day 15
9. Systemic or inhaled corticosteroids within 3 months prior to screening (Phase 1 only).
10. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARCT-032, Healthy Adults; Ascending single doses of ARCT-032 administered to healthy adults via nebulizer	Drug: ARCT-032; ARCT-032 is messenger RNA (mRNA) coding for cystic fibrosis transmembrane conductance regulator (CFTR) protein, formulated in a lipid nanoparticle (LNP).
Placebo Comparator: Placebo, Healthy Adults; Single doses of 0.9% Saline administered to healthy adults via nebulizer	Other: Placebo; Normal saline
Experimental: ARCT-032,. Adults with Cystic Fibrosis; Two doses of ARCT-032 administered to adults with Cystic Fibrosis via nebulizer	Drug: ARCT-032; ARCT-032 is messenger RNA (mRNA) coding for cystic fibrosis transmembrane conductance regulator (CFTR) protein, formulated in a lipid nanoparticle (LNP).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and dose-relationship of AEs	Safety and tolerability of ARCT-032 assessed by determining the incidence, severity and dose-relationship of AEs by dose	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma area under the curve after single dose of ARCT-032	Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point	Up to 2 Weeks
Maximum observed plasma concentration (Cmax) after single dose of ARCT-032	The maximum observed plasma concentration (Cmax)	Up to 2 Weeks
Time at which Cmax occurred after single dose of ARCT-032	The time at which Cmax occurred (Tmax)	Up to 2 Weeks
AUC0-inf after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	AUC from time zero extrapolated to infinity	Up to 2 Weeks
T1/2 after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	Terminal half-life	Up to 2 Weeks
CL after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	Total body clearance, calculated as dose divided by AUC0-inf	Up to 2 Weeks
Vss after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	Volume of distribution	Up to 2 Weeks

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.
• Collaborators: Novotech CRO
• Investigators: Study Director: Clinical Program Director, Arcturus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis, CF
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: ARCT-032-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No