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

• ClinicalTrials.gov Identifier: NCT05712538
• Recruitment Status: Recruiting
• First Posted: February 3, 2023
• Last Update Posted: December 4, 2023
• Sponsor: Arcturus Therapeutics, Inc.
• Collaborator: Novotech CRO
• Information provided by (Responsible Party): Arcturus Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 26, 2023
• First Posted Date: February 3, 2023
• Last Update Posted Date: December 4, 2023
• Actual Study Start Date: February 15, 2023
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2023)

Incidence, severity and dose-relationship of AEs [ Time Frame: 4 weeks ]

Safety and tolerability of ARCT-032 assessed by determining the incidence, severity and dose-relationship of AEs by dose

Original Primary Outcome Measures (submitted: January 26, 2023)

Incidence, severity and dose-relationship of AEs [ Time Frame: [Time Frame: 4 weeks] ]

Safety and tolerability of ARCT-032 assessed by determining the incidence, severity and dose-relationship of AEs by dose

Current Secondary Outcome Measures (submitted: November 29, 2023)

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

Original Secondary Outcome Measures (submitted: January 26, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Pharmacokinetics of ARCT-032 in Healthy Adult Subjects and Adults With Cystic Fibrosis.
• Official Title: 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
• Brief Summary: 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).

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
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double-blind, placebo controlled (Phase 1 only)

Masking: Double (Participant, Investigator)
Masking Description:

Participant and investigator masking only applies to Phase 1 healthy volunteers only. For Phase 1b, there is no masking, None (Open Label) should be applied.

Primary Purpose: Treatment

• Condition: Cystic Fibrosis

Intervention

• Drug: ARCT-032
  ARCT-032 is messenger RNA (mRNA) coding for cystic fibrosis transmembrane conductance regulator (CFTR) protein, formulated in a lipid nanoparticle (LNP).
• Other: Placebo
  Normal saline

Study Arms

• Experimental: ARCT-032, Healthy Adults
  Ascending single doses of ARCT-032 administered to healthy adults via nebulizer
  Intervention: Drug: ARCT-032
• Placebo Comparator: Placebo, Healthy Adults
  Single doses of 0.9% Saline administered to healthy adults via nebulizer
  Intervention: Other: Placebo
• Experimental: ARCT-032,. Adults with Cystic Fibrosis
  Two doses of ARCT-032 administered to adults with Cystic Fibrosis via nebulizer
  Intervention: Drug: ARCT-032

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 29, 2023): 38
• Original Estimated Enrollment (submitted: January 26, 2023): 32
• Estimated Study Completion Date: May 30, 2024
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Clinical Trial Disclosure Manager; (858) 900-2660; clinicaltrials@arcturusrx.com

• Listed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT05712538
• Other Study ID Numbers: ARCT-032-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Arcturus Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Arcturus Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Novotech CRO

Investigators

• Study Director: Clinical Program Director; Arcturus Therapeutics

• PRS Account: Arcturus Therapeutics, Inc.
• Verification Date: November 2023