Itepekimab for Bronchiectasis

Recruiting at201 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sanofi

Must not be taking: Antimicrobials, Immunosuppressants

Disqualifiers: Cystic fibrosis, Immunodeficiency, Tuberculosis, Autoimmune, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

ACT18018 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study with 3 treatment groups. The purpose of this study is to evaluate efficacy, safety and tolerability with 2 dosing regimens of itepekimab compared with placebo in male and/or female participants with NCFB aged 18 years of age up to 85 years of age (inclusive). Study details include: * The study duration (screening, 24-52-week treatment, 20-week safety follow-up) will be up to 47-77 weeks. * The treatment duration will be up to 24-52 weeks. * The follow-up duration will be 20 weeks. * Site/phone visits are at a monthly interval.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on treatment for tuberculosis, allergic bronchopulmonary aspergillosis, or using immunosuppressive therapy for autoimmune disease, you may not be eligible to participate.

How is the drug itepekimab unique for treating bronchiectasis?

Itepekimab is unique because it is a monoclonal antibody that targets interleukin-33 (IL-33), which is involved in airway inflammation. This mechanism is different from traditional treatments like corticosteroids, which broadly suppress the immune system, whereas itepekimab specifically targets a pathway involved in inflammation. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for adults aged 18-85 with non-cystic fibrosis bronchiectasis (NCFB), who've had at least 2 moderate or 1 severe lung flare-up in the past year. They should have symptoms like cough, mucus, or frequent infections and a certain level of lung function.

Inclusion Criteria

I have had 2 moderate or 1 severe lung flare-up in the last year.

Participants with a FEV1 % predicted ≥30%

I am between 18 and 85 years old.

Exclusion Criteria

I have had cancer within the last 5 years.

History of lung transplantation

Known or suspected immunodeficiency disorder

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-3 weeks

Treatment

Participants receive either itepekimab or placebo with dosing regimens of every 2 or 4 weeks for up to 52 weeks

24-52 weeks

Monthly site/phone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Monthly site/phone visits

Treatment Details

Interventions

• Itepekimab (Monoclonal Antibodies)

Trial Overview The study compares two doses of Itepekimab (an experimental drug) against a placebo to see which is better for NCFB. Participants are randomly assigned to one of three groups and will be monitored through visits or calls each month for up to about a year and a half.

Participant Groups

Group I: Itepekimab Q4W Experimental Treatment 2 Interventions

SC administration of Itepekimab every 4 weeks (Q4W) with alternating placebo administration at the 2week interval between active IMP as SC injection for up to 52 weeks

Group II: Itepekimab Q2W Experimental Treatment 1 Intervention

Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks

Group III: Placebo Placebo Group 1 Intervention

SC administration of matching placebo Q2W for up to 52 weeks

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

In a study of 14 asthmatic patients with allergic bronchopulmonary aspergillosis (ABPA), treatment with itraconazole for at least 12 months led to significant clinical improvements, including increased pulmonary function and reduced blood eosinophilia and serum IgE levels.

Itraconazole also allowed for a reduction in the use of oral glucocorticoids, with 7 out of 14 patients able to completely stop glucocorticoid therapy, highlighting its potential as an effective alternative treatment for ABPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Salez, F., Brichet, A., Desurmont, S., et al.[2019]

Itepekimab, a monoclonal antibody targeting interleukin-33, was found to be safe and well-tolerated in two phase I studies involving 63 participants, with no treatment-emergent anti-drug antibody responses detected.

The drug demonstrated effective pharmacokinetics with a long half-life and significant effects on reducing IL-33 levels and blood eosinophils, indicating its potential to reduce airway inflammation in asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. Kosloski, MP., Kalliolias, GD., Xu, CR., et al.[2022]

In a phase 2a trial involving 343 patients with moderate-to-severe COPD, itepekimab did not significantly reduce the overall rate of acute exacerbations compared to placebo, but showed promising results in former smokers, with a 42% reduction in exacerbation rates and improved lung function.

Genetic analyses indicated that certain IL-33 pathway variants are associated with COPD risk, suggesting a potential mechanism for how itepekimab may work, particularly in patients with specific genetic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Rabe, KF., Celli, BR., Wechsler, ME., et al.[2022]

In a phase 2 trial involving 296 adults with moderate-to-severe asthma, itepekimab, a monoclonal antibody targeting interleukin-33, significantly reduced the incidence of asthma control loss compared to placebo, with 22% of patients experiencing loss of control versus 41% in the placebo group.

Itepekimab also improved lung function and quality of life, while showing a similar safety profile to other treatments, indicating its potential as an effective new therapy for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. Wechsler, ME., Ruddy, MK., Pavord, ID., et al.[2021]

Allergic bronchopulmonary aspergillosis (ABPA) is often underdiagnosed in asthmatic and cystic fibrosis patients, leading to recurrent respiratory issues that typically respond to corticosteroid treatment.

Long-term corticosteroid use can have adverse effects, prompting interest in antifungal treatments like itraconazole, which may serve as a corticosteroid-sparing option, especially for patients with poor response to corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Vlahakis, NE., Aksamit, TR.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of allergic bronchopulmonary aspergillosis. [2013]