Clinical trial NCT04262167: Human Autologous Lung Stem Cell Transplant for Idiopathic Pulmonary Fibrosis
Official title: A Phase I, Randomized Study of the Safety and Efficacy of Intravenous Delivery of Lung Spheroid Stem Cells (LSCs) in Patients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis and Progressive Fibrotic Interstitial Lung Disease
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2020-02-10
Enrollment: 24
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Purpose:

To demonstrate the safety and efficacy of autologous Lung Spheroid Stem Cells (LSCs) administered by intravenous infusion in patients with idiopathic pulmonary fibrosis Progressive Fibrotic Interstitial Lung Disease.

Participants:

Patients with Idiopathic Pulmonary Fibrosis (IPF) and Progressive Fibrotic Interstitial Lung Disease

Procedures (methods):

24 patients previously diagnosed with idiopathic pulmonary fibrosis or Progressive Fibrotic Interstitial Lung Disease meeting all inclusion/exclusion criteria will be evaluated at baseline. LSCs will be grown from autologous trans-bronchial pulmonary biopsy specimens. The first group, consisting of 6 patients will be randomized after completion of the screening procedures to either a treatment group of 100 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. The second group of 18 patients will be randomized after completion of the screening procedures to either a treatment group of 200 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. Patients will be randomized using permuted blocks in a 2:1 LSC to control group ratio, providing a distribution of 8:4:12 patients among the control, low dose, and high dose groups, respectively. If the patient is randomized and 100 million LSCs are not achieved, then the patient will be analyzed separately and another patient enrolled. Intravenous infusion of LSCs will take place 4-8 weeks after the pulmonary biopsies are obtained. All patients will be followed up at months 0.5, 1, 3, 6, 9, 12, 18, and 24 after infusion to complete the safety and efficacy assessments listed herein. All patients will receive standard of care for their IPF.


Eligibility criteria: Inclusion Criteria:

* Male or female between the ages of 40 to 80.
* Diagnosis of a Progressive Fibrotic Interstitial Lung Disease
* Diagnosis of IPF based on the following criteria in accordance with American Thoracic Society (ATS) guidelines for diagnosing IPF:

  1. Definite usual interstitial pneumonia (UIP) confirmed on surgical lung biopsy (SLB) with all other etiologies for UIP excluded OR High resolution CT scan (HRCT) showing definite UIP with all other etiologies for UIP excluded.
  2. Probable UIP on both imaging and surgical lung biopsy with all other etiologies for UIP excluded.
* Forced vital capacity (FVC) greater than 50% of predicted with a ratio of forced expiratory volume in 1 second to FVC (FEV1/FVC) greater than 0.75 (Pulmonary function tests must be completed no more than 90 days before screening).
* Diffusing capacity for carbon monoxide (DLCO) greater than 25% of predicted capacity.
* Ability to perform a 6-Minute Walk Test (6MWT) at screening.
* Competency to understand the information given in the Human Research and Ethics Committee (HREC) approved Informed Consent Form and must sign the form prior to the initiation of any study procedures

Exclusion Criteria:

* Diagnosis of an interstitial lung disease (ILD) or restrictive lung disease other than IPF or Progressive Fibrotic Interstitial Lung Disease.
* Obstructive lung disease as determined by evidence of airflow obstruction on HRCT or physiologic criteria including: FEV1/FVC ratio less than 0.75, Residual volume (RV) greater than 120% by plethysmography or significant (verified by radiologist) emphysema on HRCT or evidence of reactive airway disease by change in FEV1 of greater than 12% following bronchodilator challenge.
* Evidence of sustained improvement lung function defined as improvement from pre-therapy pulmonary function tests (PFTs) observed with two or more successive post-therapy PFTs over the year prior to randomization.
* Active or recent (less than 60 days prior to enrollment) significant respiratory tract infections, or a history of frequent (greater than 2 per year for the last 2 years) infective exacerbations of IPF.
* Hospitalization within 60 days of screening for an acute exacerbation of IPF (AE-IPF).

Chronic heart failure (NYHA class III/IV) or known left ventricular ejection fraction less than 45%.

* Acute or chronic impairment (other than dyspnea) which limits the ability to comply with study requirements and procedures including the 6MWT.
* Subject requires hemodialysis, peritoneal dialysis or hemofiltration.
* Infection with HIV
* Viral Hepatitis
* Resting oxygen requirements or \>4 L of nasal canula oxygen needed with exertion

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Through study completion, 24 months
measure: Number of Participants With Hematological Parameters of Potential Clinical Importance
timeFrame: Through study completion, 24 months
measure: Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance
timeFrame: Through study completion, 24 months
Secondary outcomes:
measure: Change from Baseline in High Resolution CT scan Fibrosis Score (0-50)
timeFrame: screening visit prior to infusion and 12 months after infusion
measure: Change from baseline in Forced Vital Capacity (FVC)
timeFrame: screening visit prior to infusion and 360days post infusion
measure: Change from baseline in 6 minute walk test distance (meters)
timeFrame: screening visit prior to infusion and 360days post infusion
measure: Change from baseline in Diffusion capacity of the lung for carbon monoxide (DLCO)
timeFrame: screening visit prior to infusion and 360days post infusion
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina as Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Leonard Lobo, MD
role: PRINCIPAL_INVESTIGATOR
References: