A Phase 2, Open-label, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Efficacy of ARCT-032 in People with Cystic Fibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arcturus Therapeutics Europe B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

completed 3 Feb 2026

Decision date (initial)

2025-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Arcturus Therapeutics, Inc.

External identifiers

EU CT number

2024-517663-23-01

ClinicalTrials.gov

NCT06747858

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Dose response, Pharmacodynamic

To assess the safety and tolerability of ARCT-032 in people with CF.

Secondary objectives 2

1. To assess the pharmacokinetics (PK) of ARCT-032 in people with CF.
2. To assess the pharmacodynamic (PD) activity of ARCT-032 as determined by changes in lung function and quality of life.

Conditions and MedDRA coding

Cystic Fibrosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Able to comprehend and willing to voluntarily sign and date an informed consent form (ICF) approved by an independent ethics committee (EC)/institutional review board (IRB) before initiation of any screening or study-specific procedures; willing and able to comply with study procedures (including ability to perform acceptable and reproducible/repeatable spirometry) and complete all study visits.
2. 7. Screening test results must fall within these limits: a. Liver chemistries (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase) <3 × the upper limit of normal (ULN), and total bilirubin <1.5 × ULN. b. Estimated glomerular filtration rate (eGFR) >45 L/min/1.73m2 calculated by Modification to Diet in Renal Disease [MDRD] study equation. c. Hemoglobin ≥10 g/dL. d. Absence of clinically significant abnormality on ECG regarding rate, rhythm, or conduction.
3. 8. Females must be non-pregnant and non-lactating and if a woman of child-bearing potential (WOCBP) engaged in heterosexual relations, agree to use a highly effective contraceptive method from the time of signing the ICF until at least 30 days after the last dose of study drug. Females who are not WOCBP do not require contraception.
4. 2. Adult male or female, at least 18 years old on the day of signing the ICF.
5. 3. Confirmed diagnosis of CF documented in subject’s medical record or patient registry (2 CF-causing mutations and/or sweat chloride value ≥60 mmol/L with history of chronic sinopulmonary disease).
6. 4. Not eligible for CFTR modulator therapy (e.g., 2 null mutations) or not taking CFTR modulators for at least [CCI] days prior to [CCI] (e.g., due to drug intolerance, poor response, or lack of access to modulators).
7. 5. Forced expiratory volume in 1 second (FEV1) at screening between 40% to 100% (inclusive) of predicted value for age, sex, and height (equations of the current Global Lung Function Initiative standards) at Screening.
8. 6. Stable pulmonary status, specifically no acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within [CCI] days of [CCI].
9. 9. Males who are engaged in sexual relations with a nonpregnant WOCBP must agree to use condoms from Day 1 through 90 days after the last dose of ARCT-032, and have their female partner use a highly effective contraceptive method (see Section 4.1.2) from the signing of the ICF until at least 90 days after the last dose of study drug. Males who are incapable of fathering a child (documented bilateral absence of the vas deferens or bilateral vasectomy with confirmation of aspermia or bilateral orchiectomy) or their female partner will not be required to use birth control during the study. However, all males with partners who are pregnant must use condoms from [CCI] through [CCI] to ensure that the fetus is not exposed to the study drug.
10. 10. Confirm that the subject had a standard CF clinic visit with routine clinical screening exams/tests (including sputum culture) according to the latest clinical guidelines (Goetz 2024) within 3 months of the Screening visit. If the subject has not performed the routine screening, this shall be completed during Screening and prior to dosing Day 1.

Exclusion criteria 7

1. 1. Presence of any co-morbidities or medical conditions that, in the opinion of the investigator, might pose an additional risk by administering study drug to the participant or may confound the results of the study. This includes but is not limited to the following: a. Uncontrolled asthma or allergic bronchopulmonary aspergillosis (ABPA) within a year of screening. b. Cirrhosis with portal hypertension and known esophageal varices. c. History of massive hemoptysis [CCI] within 3 months of screening. d. Major surgery within 3 months of screening. e. Prior pulmonary malignancy, any active malignancy, current chemotherapy, or any malignancy with a natural history or treatment that has the potential to interfere with safety or efficacy assessments. f. Solid organ or hematologic transplant. g. Known history of or positive test for human immunodeficiency virus (HIV) or chronic hepatitis B. History of hepatitis C is permitted if the subject was treated and there is documentation of a cure. h. History of known sensitivity to [CCI] or liposomal products. i. Must not require supplemental oxygen while awake, or >2 L per minute while sleeping.
2. 2. History of drug or alcohol dependence within 6 months prior to Screening that may preclude adherence to the protocol, in the opinion of the investigator.
3. 3. Smoking or vaping tobacco or cannabis products within [CCI] of Screening; must be willing to abstain throughout the study period"
4. 4. Treatment with another investigational drug or biologic agent within 30 days of screening or 5 halflives of investigational drug, whichever is longer
5. 5. Prior treatment with gene therapy for CF. Individual exceptions may be made in the case of investigational gene therapies that have only temporary benefit.
6. 6. Chronic maintenance systemic corticosteroid use is permitted but doses must not exceed the equivalent of 15 mg oral prednisone daily or 30 mg every other day. No corticosteroid bursts for at least 2 months prior to [CCI].
7. 7. Unable to tolerate [CCI] (also known as [CCI]).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. AEs, adverse events of special interest (AESIs), and serious adverse events (SAEs) (incidence, severity, dose relationship).
2. Changes from baseline in vital signs and physical examinations.
3. Changes from baseline in laboratory test results.
4. Evaluation for bronchospasm (changes from pre-dose to post-dose FEV1).

Secondary endpoints 3

1. Plasma pharmacokinetics of ARCT-032 based on the observed concentrations of mRNA-[CCI] in plasma after single and multiple doses of ARCT-032.
2. Mean absolute change from baseline in pre-dose percent predicted FEV1 on Day [CCI] of the treatment period.
3. Change from baseline in Cystic Fibrosis Questionnaire – Revised Respiratory Symptoms Scale (CFQ-R RSS) score on Day [CCI].

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arcturus Therapeutics Europe B.V.

Sponsor organisation

Arcturus Therapeutics Europe B.V.

Address

Claude Debussylaan 10

City

Amsterdam

Postcode

1082 MD

Country

Netherlands

Scientific contact point

Organisation

Arcturus Therapeutics Europe B.V.

Contact name

David Geller

Public contact point

Organisation

Arcturus Therapeutics Europe B.V.

Contact name

David Geller

Third parties 20

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications