A Phase 1/2 Trial of SP-101 for the Treatment of Cystic Fibrosis (CF)

Official title

A Single Ascending Dose, Phase 1/2 Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of SP-101 Via Nebulizer for the Treatment of Cystic Fibrosis (CF)

Overview

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.

Detailed description

This multi-center study is a first-in-human, single ascending dose, Phase 1/2 trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of various dose levels in people with CF who are ineligible or intolerant to CFTR modulator therapy.

Interventions

• Combination product SP-101 and doxorubicin Cohort 1
  Single inhaled dose of SP-101 and doxorubicin Dose 1
• Combination product SP-101 and doxorubicin Cohort 2
  Single inhaled dose of SP-101 and doxorubicin Dose 2

Primary outcome measures

• Incidence and severity of adverse events [Time frame: 52 weeks]

Eligibility criteria

Inclusion criteria

• Males or females, age 18 to 65 years at Screening Visit, inclusive
• Diagnosis of CF
• ppFEV1 value between 50-100% (inclusive)
• Resting oxygen saturation ≥94% on room air by pulse oximetry 5 . Clinically stable CF disease as assessed by the Investigator and not requiring any new class of interventional treatment within the last 3 months prior to Screening

Exclusion criteria

• Any change in established pulmonary treatment (including antibiotics) within 28 days prior to Screening Visit. However, inhaled beta-agonists can be included within 2 weeks prior to Screening Visit.
• Clinically significant episode of hemoptysis (>50 mL or ¼ cup or 10 teaspoons per day) within 12 weeks prior to dosing with study drug on Day 1
• Lung infection with Mycobacterium abscessus associated with a more rapid decline in pulmonary status
• Currently receiving treatment for active lung infection with Burkholderia cenocepacia or Burkholderia dolosa
• History of solid organ or hematological transplantation
• History of clinically significant cirrhosis with or without portal hypertension
• History of pulmonary hypertension
• History of cardiotoxicity, a history of known coronary artery disease, and/or existing cardiomyopathy
• Current active fungal infection (not just a positive culture), acute blood, lung, or bladder infection, clinically significant hepatic or renal dysfunction, and/or viral infection (including human immunodeficiency virus or hepatitis virus B or C) requiring the initiation of new therapy within 30 days prior to Screening
• History of allergic bronchopulmonary aspergillosis (ABPA)
• Uncontrolled diabetes mellitus, as evidenced by hemoglobin A1c >9% at Screening
• Clinically significant laboratory abnormalities at Screening
• Subjects with any medical condition or abnormal laboratory result that, in the opinion of the Investigator, will interfere with the safe completion of the study
• Subjects who received any investigational products within 30 days (or 5 therapeutic half-lives, whichever is longer) prior to Screening
• Subjects who have previously received any gene therapy agent
• Subjects with known sensitivity to SP-101, doxorubicin or its excipients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• University of Kansas Medical Center — Kansas City
• Boston Children's Hospital, Brigham & Women's Hospital — Boston
• Columbia University — New York
• Hospital at University of Pennsylvania — Philadelphia

Publications

• Excoffon KJDA, Smith MD, Falese L, Schulingkamp R, Lin S, Mahankali M, Narayan PKL, Glatfelter MR, Limberis MP, Yuen E, Kolbeck R. Inhalation of SP-101 Followed by Inhaled Doxorubicin Results in Robust and Durable hCFTRDeltaR Transgene Expression in the Airways of Wild-Type and Cystic Fibrosis Ferrets. Hum Gene Ther. 2024 Sep;35(17-18):710-725. doi: 10.1089/hum.2024.064. Epub 2024 Sep 4. PMID 39155828
• Excoffon KJDA, Lin S, Narayan PKL, Sitaraman S, Jimah AM, Fallon TT, James ML, Glatfelter MR, Limberis MP, Smith MD, Guffanti G, Kolbeck R. SP-101, A Novel Adeno-Associated Virus Gene Therapy for the Treatment of Cystic Fibrosis, Mediates Functional Correction of Primary Human Airway Epithelia From Donors with Cystic Fibrosis. Hum Gene Ther. 2024 Sep;35(17-18):695-709. doi: 10.1089/hum.2024.063. E PMID 39155805

Identifiers

NCT: NCT06526923 · CFAAV-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗