A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1)

A Seamless Phase I/II Trial With an Initial Open-label Dose Escalation Part and a Subsequent Randomised, Double-blind, Placebo-controlled Expansion Part to Evaluate the Safety, Tolerability, and Efficacy of a Single Dose of BI 3720931, an Inhaled Lentiviral Vector Gene Therapy, in Adult People With Cystic Fibrosis Who Are Ineligible for CFTR Modulators (Lenticlair 1)

This study is open to adult men with cystic fibrosis and adult women with cystic fibrosis who cannot have children. People with cystic fibrosis can join if they are not eligible to receive cystic fibrosis transmembrane conductance regulator modulator therapy (CFTR-MT). The purpose of this study is to find out how well a medicine called BI 3720931 is tolerated and whether it improves lung function in people with cystic fibrosis. In this study, BI 3720931 is given to humans for the first time.

This study has two phases. In Phase 1, participants are put in one of 3 groups, one group after the other. Each group gets a different dose of BI 3720931. Group 1 starts with the lowest dose, followed by group 2 with the middle and group 3 with the high dose. In Phase 2, participants are put into 3 groups by chance, but at the same time. 2 groups get different doses of BI 3720931 selected based on results of Phase 1, and 1 group gets placebo. All study participants get only 1 dose of BI 3720931 or placebo and they use a special inhaler to take the study medicine. The placebo inhaler looks like the BI 3720931 inhaler but does not contain any medicine. During the study, participants continue taking their usual medicines.

Doctors closely monitor participants' health at the study site for the first 3 days after receiving BI 3720931. Participants visit their doctors regularly thereafter. The doctors check the health of the participants and note any health problems that could have been caused by BI 3720931. Study participants regularly do a standard lung function test to measure how well their lungs are working. Participants, in either Phase 1 or Phase 2, are in the study for 7 months. After completion of this study, participants will take part in a long-term follow-up study (1504-0003).

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Genetic: BI 3720931; Device: Inhaler

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac
• Italy
  • Roma, Italy, 00165
    • Osp. Pediatrico Bambin Gesù
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
• United Kingdom
  • London, United Kingdom, SW3 6JY
    • Royal Brompton Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

• Cystic fibrosis (CF)-pulmonary phenotype and a confirmed diagnosis of CF:

  • Positive sweat chloride ≥60 mmol/L by pilocarpine iontophoresis OR
  • Genotype with 2 identifiable CF-causing mutations accompanied by one or more clinical features if sweat chloride testing is between 30 and 59 mmol/L
• Trial participants who are not eligible for treatment with cystic fibrosis transmembrane conductance regulator modulator therapy (CFTRmt) due to their genotype with 2 identified CFTR-mutations (including Class I CFTR gene mutations) and are also not expected to become eligible during the trial according to investigator´s opinion
• Trial participants able to perform acceptable spirometric maneuvers according to American Thoracic Society/European Respiratory Society 2019 standards
• Forced expiratory volume in 1 second, percent of predicted value (FEV1pp) ≥50% and ≤100% of predicted normal at Visit 1. Predicted value based on Global Lung Initiative lung function reference equations
• Stable CF disease with no pulmonary exacerbation 4 weeks prior to the screening visit and during the screening period and stable drug- and non-drug therapy for CF in the 4 weeks prior to dosing Further inclusion criteria apply.

Key exclusion criteria:

• Trial participants not eligible for CFTRmt based on contraindications (e.g. liver failure) or who needed to withdraw CFTRmt due to intolerability are not appropriate candidates for this Phase I/II trial
• Trial participants requiring chronic use of systemic corticosteroids or immunosuppressants to treat another condition Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Dose group 1 (low dose)	Genetic: BI 3720931; BI 3720931; Device: Inhaler; Inhaler for application of BI 3720931 and placebo
Experimental: Phase I: Dose group 2 (medium dose)	Genetic: BI 3720931; BI 3720931; Device: Inhaler; Inhaler for application of BI 3720931 and placebo
Experimental: Phase I: Dose group 3 (high dose)	Genetic: BI 3720931; BI 3720931; Device: Inhaler; Inhaler for application of BI 3720931 and placebo
Experimental: Phase II: Dose group 1	Genetic: BI 3720931; BI 3720931; Device: Inhaler; Inhaler for application of BI 3720931 and placebo
Experimental: Phase II: Dose group 2	Genetic: BI 3720931; BI 3720931; Device: Inhaler; Inhaler for application of BI 3720931 and placebo
Placebo Comparator: Phase II: Placebo group	Drug: Placebo; Placebo; Device: Inhaler; Inhaler for application of BI 3720931 and placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: Occurrence of any drug-related, treatment-emergent adverse events (AE) up to Week 24 after drug administration	up to 24 weeks
Phase II: Absolute change from baseline in forced expiratory volume in 1 second, percent of predicted value (FEV1pp) at Week 8 after drug administration	at baseline, at week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase I: Occurrence of treatment response defined as change from baseline ≥5% in FEV1pp, comparing the mean of 3 pre-treatment FEV1pp measured in the screening period with the mean of 3 post-treatment FEV1pp-values at Weeks 4, 6, and 8	up to 12 weeks
Phase I: Absolute change from baseline in FEV1pp at Week 24 after drug administration	at baseline, at week 24
Phase I: Occurrence of any dose limiting toxicities (DLTs) up to Week 24 after drug administration	up to 24 weeks
Phase II: Absolute change from baseline in FEV1pp at Week 24 after drug administration	at baseline, at week 24
Phase II: Occurrence of any serious adverse events (SAEs) up to Week 24 after drug administration	up to 24 weeks
Phase II: Occurrence of any drug-related, treatment-emergent AEs up to Week 24 after drug administration	up to 24 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Actual): February 3, 2026
• Study Completion (Actual): February 3, 2026

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; Equipment and Supplies; Nebulizers and Vaporizers
• Other Study ID Numbers: 1504-0001; 2023-503281-23-00 (Registry Identifier: CTIS); U1111-1291-0800 (Registry Identifier: WHO International Clinical Trials Registry Platform (ICTRP)); 1504.1 (Other Identifier: Sponsor ID)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing

• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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