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.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: ARCT-032; Other: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• 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
• 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
• Actual Study Start Date: February 15, 2023
• Estimated Primary Completion Date: May 30, 2024
• Estimated Study Completion Date: May 30, 2024

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. Maximum observed plasma concentration (Cmax) after single dose of ARCT-032 [ Time Frame: Up to 2 Weeks ]
   The maximum observed plasma concentration (Cmax)
3. Time at which Cmax occurred after single dose of ARCT-032 [ Time Frame: Up to 2 Weeks ]
   The time at which Cmax occurred (Tmax)
4. 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
5. T1/2 after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032 [ Time Frame: Up to 2 Weeks ]
   Terminal half-life
6. 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
7. Vss after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032 [ Time Frame: Up to 2 Weeks ]
   Volume of distribution

Eligibility Criteria

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

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

Contacts and Locations

Contacts

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

Locations

New Zealand

New Zealand Clinical Research; Recruiting

Christchurch, New Zealand, 8011

Contact: Olivia Dempster arctic@nzcr.co.nz

Principal Investigator: Christian Schwabe, MD

Sponsors and Collaborators

Arcturus Therapeutics, Inc.

Novotech CRO

Investigators

• Study Director: Clinical Program Director; Arcturus Therapeutics

More Information

• Responsible Party: Arcturus Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05712538
• Other Study ID Numbers: ARCT-032-01
• First Posted: February 3, 2023
• Last Update Posted: December 4, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Arcturus Therapeutics, Inc.:

Cystic Fibrosis, CF

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases