Gene Therapy for Cystic Fibrosis

(SAAVe Trial)

Recruiting in Palo Alto (17 mi)

+4 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Spirovant Sciences, Inc.

Disqualifiers: Lung infection, Transplant history, Cirrhosis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 CFTR modulator therapy.

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.

What data supports the effectiveness of the treatment SP-101, Spirovant's AAV gene therapy, for cystic fibrosis?

Research on similar AAV-based gene therapies for cystic fibrosis has shown that while they are safe and well-tolerated, they have not yet demonstrated significant improvements in lung function. However, the approach holds promise as gene therapy is considered a potential way to correct the genetic defect causing cystic fibrosis. ^{1 2 3 4 5}

How is the SP-101 treatment for cystic fibrosis different from other treatments?

SP-101 is a gene therapy that uses an adeno-associated virus (AAV) to deliver a healthy version of the CFTR gene directly to the lungs, aiming to correct the underlying genetic defect in cystic fibrosis, which is different from traditional treatments that mainly manage symptoms. ^{1 3 4 6 7}

Research Team

Jessica Lee, MPH

Principal Investigator

Spirovant Sciences

Eligibility Criteria

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.

I am between 18 and 65 years old.

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.

Trial Timeline

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

Treatment Details

Interventions

• SP-101 (Gene Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

rAAV-CFTRΔR Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice. [2022]

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

Calculating expected lung deposition of aerosolized administration of AAV vector in human clinical studies. [2013]

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

Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trial. [2012]

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

Gene therapy for cystic fibrosis: an example for lung gene therapy. [2020]

6. Brazil pubmed.ncbi.nlm.nih.gov

Adeno-associated virus for cystic fibrosis gene therapy. [2019]

7. United States 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. [2019]