Nebulized KB407 for Cystic Fibrosis

Recruiting at 5 trial locations

Overseen By David Sweet, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Krystal Biotech, Inc.

Disqualifiers: Organ transplant, Substance abuse, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KB407 to determine its safety and tolerability for adults with cystic fibrosis, a condition that affects the lungs and makes breathing difficult. The study will explore different doses of KB407 delivered through a nebulizer, a device that turns liquid medicine into mist. It is suitable for adults diagnosed with cystic fibrosis who are currently stable in their condition. Participants will receive one, two, or four doses of the treatment to help researchers assess its effectiveness. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot start any new chronic therapies or change existing ones (except for pancreatic enzyme replacement therapy) within 28 days before the first dose.

Is there any evidence suggesting that KB407 is likely to be safe for humans?

Research has shown that KB407, a treatment for cystic fibrosis, is safe and well-tolerated in studies so far. Reports indicate that patients who received different doses of KB407 experienced no major side effects. This suggests that the treatment is generally well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis?

Researchers are excited about KB407 for cystic fibrosis because it offers a novel approach by using a nebulized delivery method. This treatment involves inhaling the medication directly into the lungs, which could enhance its effectiveness compared to oral or systemic therapies. Unlike standard treatments that mostly manage symptoms or fight infections, KB407 aims to address the underlying genetic cause of cystic fibrosis by delivering a corrected version of the faulty gene directly to the lungs. This direct targeting could potentially improve lung function more effectively and with fewer side effects.

What evidence suggests that nebulized KB407 might be an effective treatment for cystic fibrosis?

Research suggests that KB407, the investigational treatment in this trial, might help treat cystic fibrosis by creating a normal version of the CFTR protein, crucial for healthy lungs. Earlier studies in mice and primates showed that KB407 can safely deliver this healthy CFTR protein to the lungs. This delivery may improve the flow of ions and water in and out of lung cells, potentially enhancing lung health. Although more research is needed in humans, these early results offer promise for people with cystic fibrosis. ^{2 4 6 7 8}

Who Is on the Research Team?

David Chien, MD

Principal Investigator

Senior Vice President of Clinical Development

Are You a Good Fit for This Trial?

Adults with cystic fibrosis who understand and agree to the study's procedures can join. They must have a confirmed diagnosis, stable health, specific lung function levels, normal oxygen saturation without assistance, and two CFTR gene mutations. Excluded are those recently ill or hospitalized, vaccinated close to treatment start, on certain antibiotics recently or with conditions that could affect safety assessments.

Inclusion Criteria

I have two CFTR gene mutations causing my condition.

The subject must have read, understood, and signed an Institutional Review Board/Ethics Committee (IRB/IEC) approved Informed Consent Form and must be able to and willing to follow study procedures and instructions

Your past sweat chloride level was higher than 60 mmol/L.

Exclusion Criteria

I have not been vaccinated within 72 hours before starting treatment and have no plans for vaccination during treatment.

I haven't been hospitalized or had a significant infection in the last 14 days.

I cannot undergo a bronchoscopy as per my doctor's advice.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ascending doses of nebulized KB407

2 months

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KB407

Trial Overview The trial is testing KB407 through nebulization to see how safe it is and how well people tolerate different doses. It's for adults with cystic fibrosis. Participants will receive ascending doses of KB407 via a nebulizer which turns liquid medication into a mist.

How Is the Trial Designed?

Group I: Cohort 3 (open label) Experimental Treatment 1 Intervention

Four administrations of KB407

Group II: Cohort 2 (open label) Experimental Treatment 1 Intervention

Two administrations of KB407

Group III: Cohort 1 (open label) Experimental Treatment 1 Intervention

A single administration of KB407

Who Is Running the Clinical Trial?

Krystal Biotech, Inc.

Lead Sponsor

Trials

15

Recruited

770+

Published Research Related to This Trial

Inhaled mannitol (400 mg) significantly improved lung function in cystic fibrosis patients, with a mean increase in FEV1 of 73.42 mL and a relative increase of 3.56% compared to a control group, based on data from 600 patients over 26 weeks.

The treatment also reduced the incidence of pulmonary exacerbations by 29%, highlighting its efficacy as an important addition to cystic fibrosis management, particularly in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis. Bilton, D., Bellon, G., Charlton, B., et al.[2016]

CFTR modulators, like VX-659 and VX-445, are being tested in phase 3 studies to improve the function of the CFTR protein in cystic fibrosis patients with the F508del mutation, which affects about 90% of patients.

These new combinations aim to enhance CFTR processing and function, potentially offering clinical benefits for patients who currently have limited treatment options due to their specific mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles. Taylor-Cousar, JL., Mall, MA., Ramsey, BW., et al.[2023]

Ivacaftor, a small molecule approved in 2012, represents a significant advancement in cystic fibrosis treatment by directly targeting the CFTR gene mutations, improving chloride channel function in specific patient genotypes.

Three main therapeutic strategies have been developed to enhance CFTR function: potentiators for class III and IV mutations, correctors for class II mutations, and production correctors for class I mutations, indicating a move towards more personalized medicine in treating cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies to improve CFTR function in cystic fibrosis. Brodlie, M., Haq, IJ., Roberts, K., et al.[2022]

A study involving 96 cystic fibrosis patients aged 6-54 years identified key inspiratory variables (like peak inspiratory flow and volume) that are crucial for designing effective dry powder inhalers (DPIs) for this population.

The research found that older patients had higher inhaled volumes and flow rates, while children had lower values, indicating that DPI designs must accommodate these differences to ensure effective drug delivery across all age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older. Tiddens, HA., Geller, DE., Challoner, P., et al.[2007]

Current nebulizers for delivering inhaled drugs in cystic fibrosis are often inefficient, leading to variability in how much medication reaches the lower respiratory tract, which is crucial for effective treatment.

Using breath-enhanced jet nebulizers can improve drug delivery compared to traditional nebulizers, especially for aerosols with smaller particle sizes (2 to 3 microns), which may enhance clinical benefits regardless of patient age or disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing a nebulizer for cystic fibrosis applications. Geller, DE.[2019]

Connecting the Up-Draft II Opti-Neb nebulizer to PEP devices significantly reduced the aerosol particle size and the amount of albuterol delivered to patients, with patient doses decreasing by 76% to 84% depending on the PEP device used.

In contrast, the LC Plus nebulizer did not show any change in aerosol characteristics or patient dose when connected to PEP devices, indicating that not all nebulizers are affected in the same way by these devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro evaluation of positive expiratory pressure devices attached to nebulizers. Berlinski, A.[2019]

The investigational PARI eFlow(®) nebulizer delivered nearly the same amount of medication to the lungs as the PARI LC STAR(®) nebulizer, but did so in less than half the time, making it a more efficient option for patients.

Both nebulizers showed similar distribution of the medication in the lungs, indicating that the eFlow(®) maintains effective delivery while improving the speed of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of amount and speed of deposition between the PARI LC STAR® jet nebulizer and an investigational eFlow® nebulizer. Coates, AL., Green, M., Leung, K., et al.[2011]

The compound c407 has shown promising results in improving CFTR function in a mouse model of Cystic Fibrosis with the F508del mutation, significantly increasing chloride conductance in nasal epithelial cells.

Long-term administration of c407 was well tolerated, and toxicological studies indicated no significant safety concerns, suggesting its potential as a therapeutic option for Cystic Fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice. da Cunha, MF., Pranke, I., Sassi, A., et al.[2022]

Cystic fibrosis (CF) has seen significant improvements in prognosis over the last 40 years due to advancements in pancreatic enzyme supplements and new drugs targeting pulmonary infections and inflammation.

Current challenges in CF treatment include correcting the underlying genetic defect and finding effective therapies for chronic respiratory infections, with ongoing clinical trials exploring new drug options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment strategies for cystic fibrosis: what's in the pipeline? Frerichs, C., Smyth, A.[2019]

In a study of 108 cystic fibrosis patients, only 30.5% achieved the maximum inhalation technique score, highlighting the need for improved inhalation practices despite 74.08% having adequate techniques overall.

Only 31.48% of patients maintained excellent nebulizer disinfection and maintenance, indicating a significant gap in adherence to recommended practices, which could impact treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulizer Care and Inhalation Technique in Children with Cystic Fibrosis. Petrocheilou, A., Kaditis, AG., Troupi, E., et al.[2020]

Citations

1. ir.krystalbio.com ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-virtual-presentation-pre-clinical-0

Krystal Biotech Announces Virtual Presentation of Pre ... By inducing expression of full length, normal CFTR protein in the lung, treatment with KB407 has potential to restore ion and water flow into and out of lung ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/krystal-biotech-kb407/

Krystal Biotech doses patients in cystic fibrosis therapy trial The trial's primary endpoint is to assess the safety and tolerability of nebulised KB407. It will also evaluate biodistribution and vector ...

3. withpower.com withpower.com/trial/phase-1-fibrosis-10-2022-c54ef

Nebulized KB407 for Cystic Fibrosis Inhaled mannitol (400 mg) significantly improved lung function in cystic fibrosis patients, with a mean increase in FEV1 of 73.42 mL and a relative increase of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05504837

A Study Assessing KB407 for the Treatment of Cystic Fibrosis Study Details | NCT05504837 | A Study Assessing KB407 for the Treatment of Cystic Fibrosis | ClinicalTrials.gov.

5. cysticfibrosisnewstoday.com cysticfibrosisnewstoday.com/news/krystal-biotech-expects-kb407-trial-after-cf-gene-therapy-found-safe-well-tolerated-animals/

KB407 Trial Expected After CF Gene Therapy Found Safe ... In studies in mice and primates, KB407 was safe and effective at delivering healthy CTFR.

6. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT05504837

A Study Assessing KB407 for the Treatment of Cystic Fibrosis This study will evaluate safety and tolerability of ascending doses of nebulized KB407 in adults with cystic fibrosis. (Show More).

7. apps.cff.org apps.cff.org/Trials/Finder?search=%7BPipelineDrugId%3A%2710221%27%2CPipelineDrugDisplayName%3A%27KB407%27%7D

Clinical Trials Finder This study will evaluate safety and tolerability of ascending doses of nebulized KB407, a gene therapy intended to deliver a new, correct copy of the CFTR ...

8. ir.krystalbio.com ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-initial-clinical-update-rare

Krystal Biotech Announces Initial Clinical Update for Rare ... Both KB408 for AATD patients and KB407 for patients with cystic fibrosis were safe and well tolerated at all dosing regimens evaluated to date.