Gene Therapy for Cystic Fibrosis

(SAAVe Trial)

Recruiting at 4 trial locations

Overseen By Spirovant.ClinicalTrials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Spirovant Sciences, Inc.

Disqualifiers: Lung infection, Transplant history, Cirrhosis, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called SP-101, designed to help people with cystic fibrosis (CF) who cannot tolerate current treatments. Participants will receive a one-time inhalation of SP-101 combined with varying doses of doxorubicin, a medication used to enhance the treatment. The goal is to determine if this combination can improve lung function and overall health in CF patients. Ideal participants are adults with CF who have not recently changed their CF treatment and do not have severe lung infections or certain other health conditions. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group of patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you should not have any changes in your established pulmonary treatment within 28 days before the screening visit. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SP-101 is a new gene therapy being tested for cystic fibrosis. In earlier studies, researchers administered SP-101 as an inhaled treatment. These studies are evaluating its safety and how the body processes it.

Reports from these studies suggest that SP-101, when combined with doxorubicin (a chemotherapy drug), is under safety monitoring. Since this trial is in its early stages, the primary focus is on ensuring the treatment's safety. Doctors and researchers are closely observing for any harmful effects and how well patients tolerate it.

As this trial is in the early phases, it primarily examines safety in humans. While researchers are still learning about side effects, the treatment has been deemed safe enough for human testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SP-101 for cystic fibrosis because, unlike traditional therapies that primarily focus on managing symptoms, SP-101 aims to address the underlying genetic cause of the disease. This treatment uses gene therapy delivered through inhalation, which is a novel method that targets lung cells directly, potentially leading to more effective and sustained results. Additionally, the combination with doxorubicin, typically used as a chemotherapy agent, might enhance the delivery and uptake of the gene therapy, offering a new avenue of hope for better management of cystic fibrosis.

What evidence suggests that SP-101 might be an effective treatment for cystic fibrosis?

Research shows that SP-101 is a promising new treatment for cystic fibrosis (CF). SP-101 uses a special virus to deliver a healthy version of the CFTR gene directly into the lungs. This gene helps produce a protein that often malfunctions in people with CF. In this trial, participants will receive a single inhalational administration of SP-101 followed by doxorubicin, with different doses tested in separate cohorts. Early results suggest that this combination may improve lung function in people with CF. This method could benefit those unable to use other CF treatments. While more research is needed, these early findings offer hope for new CF therapies. ^{1 2 3 5 6}

Who Is on the Research Team?

Jessica Lee, MPH

Principal Investigator

Spirovant Sciences

Are You a Good Fit for This Trial?

This trial is for adults with Cystic Fibrosis who can't take or haven't had success with CFTR modulator therapy. Specific details about eligibility are not provided, but typically participants need to meet certain health standards and may be excluded based on factors that could impact the study's safety or results.

Inclusion Criteria

Resting oxygen saturation ≥94% on room air by pulse oximetry measured at Screening

I have been diagnosed with cystic fibrosis.

My lung function, measured by FEV1, is within 50-100% of the expected range for someone my age, sex, and height.

Exclusion Criteria

I have never received gene therapy.

I have a history of high blood pressure in the lungs.

I am allergic to SP-101, doxorubicin, or similar medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single inhalational administration of SP-101 and doxorubicin at various dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SP-101

Trial Overview The trial is testing SP-101 gene therapy in combination with doxorubicin, an existing medication. There are two different groups (cohorts) receiving varying doses or treatment regimens to evaluate how well the new therapy works and its safety.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 2 Interventions

Single inhalational administration of SP-101 and doxorubicin Selected Dose

Group II: Cohort 2 Experimental Treatment 1 Intervention

Single inhalational administration of SP-101 and doxorubicin Dose 2

Group III: Cohort 1 Experimental Treatment 1 Intervention

Single inhalational administration of SP-101 and doxorubicin Dose 1

Who Is Running the Clinical Trial?

Spirovant Sciences, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Gene therapy is being explored as a treatment for various lung diseases, particularly cystic fibrosis (CF), which is a promising candidate due to the lack of effective treatments available.

The success of gene therapy depends on selecting the right gene transfer vector for the specific lung cell types affected by the disease, highlighting the complexity of lung structure and the need for tailored approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for cystic fibrosis: an example for lung gene therapy. Griesenbach, U., Geddes, DM., Alton, EW.[2020]

Gene therapy presents a promising alternative for treating genetic lung diseases like cystic fibrosis, which affects about 1 in 2500 live births due to mutations in the CFTR gene.

Adeno-associated virus (AAV) is highlighted as the most promising vector for delivering the CFTR gene to lung cells, as it specifically targets airway epithelial cells and is safe for human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus for cystic fibrosis gene therapy. Martini, SV., Rocco, PR., Morales, MM.[2019]

Targeted Genetics is developing a gene therapy using an AAV vector to deliver the normal CFTR gene directly to the lungs of cystic fibrosis patients, which aims to treat the underlying cause of the disease.

The therapy has received Orphan Drug Status and has progressed to phase II trials for both cystic fibrosis and sinusitis, indicating its potential efficacy and safety in treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technology evaluation: AAV-CFTR vector, targeted genetics. Tebbutt, SJ.[2012]

A larger study involving 102 subjects with cystic fibrosis found that aerosolized tgAAVCF was safe and well tolerated, confirming previous findings of safety in smaller studies.

Despite being well tolerated, tgAAVCF did not show a statistically significant improvement in lung function (FEV1) or other health markers compared to placebo, indicating that further research is needed to develop effective gene therapies for cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trial. Moss, RB., Milla, C., Colombo, J., et al.[2012]

The study determined that the aerosolized AAV vector (tgAAVCF) for cystic fibrosis gene therapy has a mass median diameter of 2.78 micrometers, which is suitable for effective lung delivery.

Using a breath-actuated nebulizer, approximately 47% of the initial dose is expected to reach the patient, with 72% of that dose deposited beyond the vocal cords, indicating a promising method for delivering gene therapy directly to the lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calculating expected lung deposition of aerosolized administration of AAV vector in human clinical studies. Leung, K., Louca, E., Munson, K., et al.[2013]

In a phase I clinical trial involving 10 cystic fibrosis patients, the AAV-CFTR vector successfully transferred CFTR cDNA to respiratory epithelial cells in the maxillary sinus, showing the highest gene transfer levels at 0.1-1 vector copies per cell.

The treatment demonstrated a favorable safety profile with minimal inflammatory or immune responses, and dose-dependent changes in sinus function were observed, indicating potential therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Wagner, JA., Messner, AH., Moran, ML., et al.[2019]

The study demonstrated that rAAV gene therapy can effectively restore chloride and fluid secretion in cystic fibrosis (CF) models, showing promise for a mutation-independent treatment applicable to all CF patients.

Treatment with the engineered rAAV vector led to functional rescue of CFTR in both human-derived organoids and CF mouse models, indicating strong potential for future clinical applications in curing CF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rAAV-CFTRΔR Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice. Vidović, D., Carlon, MS., da Cunha, MF., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06526923

Study Details | NCT06526923 | A Phase 1/2 Trial of SP-101 ... This is a Phase 1/2 multicenter, open-label, single dose trial of SP-101 investigational gene therapy in adults with CF who are ineligible for or intolerant to ...

2. liebertpub.com liebertpub.com/doi/full/10.1089/hum.2024.063

SP-101, A Novel Adeno-Associated Virus Gene Therapy ... SP-101 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a human CFTR minigene, hCFTRΔR, and is being investigated as an inhalation ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39155828/

Inhalation of SP-101 Followed by Inhaled Doxorubicin ... These data strongly support the continued development of inhaled SP-101, followed by inhaled doxorubicin, for the treatment of CF.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/spirovant-gene-therapy-trial/

Spirovant doses first subject in cystic fibrosis gene therapy ... Spirovant has announced the commencement of its Phase I/II study with the first patient receiving a dose of SP-101 to treat cystic fibrosis.

5. labiotech.eu labiotech.eu/in-depth/gene-therapy-cystic-fibrosis/

Gene therapy for cystic fibrosis gains clinical momentum AAV vectors to the rescue for cystic fibrosis ... Besides 4D-710, Spirovant Sciences' SP-101 is another AAV-based gene therapy in the making.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39155805/

SP-101, A Novel Adeno-Associated Virus Gene Therapy ... SP-101 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a human CFTR minigene, hCFTRΔR, and is being investigated as an inhalation ...