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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05712538
• Other study ID #: ARCT-032-01
• Status: Recruiting
• Phase: Phase 1
• Start date: February 15, 2023
• Est. completion date: May 30, 2024

Study information

• Verified date: November 2023
• Source: Arcturus Therapeutics, Inc.
• Contact: Clinical Trial Disclosure Manager
• Phone: (858) 900-2660
• Email: clinicaltrials[@]arcturusrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: May 30, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• 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

Locations

Country	Name	City	State
New Zealand	New Zealand Clinical Research	Christchurch

Sponsors (2)

Lead Sponsor	Collaborator
Arcturus Therapeutics, Inc.	Novotech CRO

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Maximum observed plasma concentration (Cmax) after single dose of ARCT-032	The maximum observed plasma concentration (Cmax)	Up to 2 Weeks
Secondary	Time at which Cmax occurred after single dose of ARCT-032	The time at which Cmax occurred (Tmax)	Up to 2 Weeks
Secondary	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
Secondary	T1/2 after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	Terminal half-life	Up to 2 Weeks
Secondary	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
Secondary	Vss after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032	Volume of distribution	Up to 2 Weeks