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Human Autologous Lung Stem Cell Transplant for Idiopathic Pulmonary Fibrosis (HALT-IPF)

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lung Spheroid Stem Cells 100 million
Lung Spheroid Stem Cells 200 million
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female between the ages of 50 to 80.

  • 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.
  • 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 of IPF condition 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

Sites / Locations

  • University of North Carolina as Chapel HillRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Experimental

No Intervention

Arm Label

Low Dose LSCs (cohort 1) n = 4 planned

Usual Care (Cohort 1) n = 2 planned

High Dose LSCs (Cohort 2) n = 12 planned

Usual Care (Cohort 2) n = 6 planned

Arm Description

4-8 weeks following transbronchial biopsy, participants in this arm will receive 100 million Lung Spheroid Stem Cell (LSC) infusion.

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

4-8 weeks following transbronchial biopsy, participants in this arm will receive 200 million LSC infusion.

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Number of Participants With Hematological Parameters of Potential Clinical Importance
Blood samples will be collected for the assessment of hematology parameters. The clinical concern range for the parameters will be: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8x10^9 cells per liter [cells/L]); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L).
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance
Blood samples will be collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters are: albumin (low: <30 millimoles per liter [mmol/L]); alanine aminotransferase (ALT) (high: >=2xupper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2xULN); alkaline phosphatase (ALP) (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L).

Secondary Outcome Measures

Change from Baseline in High Resolution CT scan Fibrosis Score (0-50)
Each lobe of the lung will be numerically scored on findings seen with fibrosis utilizing High resolution CT Chest (HRCT). A numerical value is assigned to a specific finding related to fibrosis, with higher values assigned to more specific findings of fibrosis. A total composite overall numerical score will be obtained for the lungs, with a maximum possible pulmonary fibrosis score of 50 (Right upper lobe, right middle lobe, right lower lobe, left upper lobe, and left lower lobe). An azygous lobe if present will be considered as part of the right upper lobe.
Change from baseline in Forced Vital Capacity (FVC)
Efficacy of therapy as measured by the annual rate of decline in FVC expressed in mL
Change from baseline in 6 minute walk test distance (meters)
A 6 minute walk test will be done at the indicated time points to determine change in exercise capacity with the intervention and meters walked in 6 minutes on a flat surface will be recorded
Change from baseline in Diffusion capacity of the lung for carbon monoxide (DLCO)
Change from baseline in DLCO, corrected for Hemaglobin (mmol/min/kPa)

Full Information

First Posted
February 6, 2020
Last Updated
March 30, 2023
Sponsor
University of North Carolina, Chapel Hill
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1. Study Identification

Unique Protocol Identification Number
NCT04262167
Brief Title
Human Autologous Lung Stem Cell Transplant for Idiopathic Pulmonary Fibrosis
Acronym
HALT-IPF
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 22, 2020 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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. Participants: Patients with Idiopathic Pulmonary Fibrosis (IPF) Procedures (methods): 24 patients previously diagnosed with idiopathic pulmonary fibrosis 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Dose LSCs (cohort 1) n = 4 planned
Arm Type
Experimental
Arm Description
4-8 weeks following transbronchial biopsy, participants in this arm will receive 100 million Lung Spheroid Stem Cell (LSC) infusion.
Arm Title
Usual Care (Cohort 1) n = 2 planned
Arm Type
No Intervention
Arm Description
Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.
Arm Title
High Dose LSCs (Cohort 2) n = 12 planned
Arm Type
Experimental
Arm Description
4-8 weeks following transbronchial biopsy, participants in this arm will receive 200 million LSC infusion.
Arm Title
Usual Care (Cohort 2) n = 6 planned
Arm Type
No Intervention
Arm Description
Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.
Intervention Type
Biological
Intervention Name(s)
Lung Spheroid Stem Cells 100 million
Other Intervention Name(s)
LSCs
Intervention Description
LSCs grown from autologous trans-bronchial biopsy specimens
Intervention Type
Biological
Intervention Name(s)
Lung Spheroid Stem Cells 200 million
Other Intervention Name(s)
LSCs
Intervention Description
LSCs grown from autologous trans-bronchial biopsy specimens
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Time Frame
Through study completion, 24 months
Title
Number of Participants With Hematological Parameters of Potential Clinical Importance
Description
Blood samples will be collected for the assessment of hematology parameters. The clinical concern range for the parameters will be: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8x10^9 cells per liter [cells/L]); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L).
Time Frame
Through study completion, 24 months
Title
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance
Description
Blood samples will be collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters are: albumin (low: <30 millimoles per liter [mmol/L]); alanine aminotransferase (ALT) (high: >=2xupper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2xULN); alkaline phosphatase (ALP) (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L).
Time Frame
Through study completion, 24 months
Secondary Outcome Measure Information:
Title
Change from Baseline in High Resolution CT scan Fibrosis Score (0-50)
Description
Each lobe of the lung will be numerically scored on findings seen with fibrosis utilizing High resolution CT Chest (HRCT). A numerical value is assigned to a specific finding related to fibrosis, with higher values assigned to more specific findings of fibrosis. A total composite overall numerical score will be obtained for the lungs, with a maximum possible pulmonary fibrosis score of 50 (Right upper lobe, right middle lobe, right lower lobe, left upper lobe, and left lower lobe). An azygous lobe if present will be considered as part of the right upper lobe.
Time Frame
screening visit prior to infusion and 12 months after infusion
Title
Change from baseline in Forced Vital Capacity (FVC)
Description
Efficacy of therapy as measured by the annual rate of decline in FVC expressed in mL
Time Frame
screening visit prior to infusion and 360days post infusion
Title
Change from baseline in 6 minute walk test distance (meters)
Description
A 6 minute walk test will be done at the indicated time points to determine change in exercise capacity with the intervention and meters walked in 6 minutes on a flat surface will be recorded
Time Frame
screening visit prior to infusion and 360days post infusion
Title
Change from baseline in Diffusion capacity of the lung for carbon monoxide (DLCO)
Description
Change from baseline in DLCO, corrected for Hemaglobin (mmol/min/kPa)
Time Frame
screening visit prior to infusion and 360days post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female between the ages of 50 to 80. Diagnosis of IPF based on the following criteria in accordance with American Thoracic Society (ATS) guidelines for diagnosing IPF: 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. 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. 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 of IPF condition 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Colleen Rice
Phone
984-974-2963
Email
colleen_rice@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonard Lobo, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina as Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caleb Hemphill
Phone
984-974-2963
Email
caleb_hemphill@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Leonard Lobo
Phone
919-966-2531
Email
jason_lobo@med.unc.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
IPD Sharing Time Frame
9 to 36 months following publication
IPD Sharing Access Criteria
IRB, IEC, or REB approval and an executed Data Use Agreement (DUA) with UNC specifying the uses of such data to be shared must be in place before any data is shared.

Learn more about this trial

Human Autologous Lung Stem Cell Transplant for Idiopathic Pulmonary Fibrosis

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