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A Study to Evaluate the Potential Role of Mesenchymal Stem Cells in the Treatment of Idiopathic Pulmonary Fibrosis (MSC in IPF)

This study has been completed.
Sponsor:
Collaborator:
Mater Medical Research Institute
Information provided by (Responsible Party):
Daniel Chambers, The Prince Charles Hospital
ClinicalTrials.gov Identifier:
NCT01385644
First received: May 4, 2011
Last updated: November 24, 2015
Last verified: November 2015
  Purpose

The primary objective of this study is to establish the feasibility and safety of infusions of placental Mesenchymal Stem Cells (MSC) from related or unrelated HLA identical or HLA mismatched donors in the treatment of Idiopathic Pulmonary Fibrosis (IPF).

The secondary objectives are to document changes in lung function, 6 minute walk distance (6MWD), gas exchange and radiological appearance following infusion of MSC over a six month evaluation period.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Other: Placental MSC
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Potential Role of Mesenchymal Stem Cells in the Treatment of Idiopathic Pulmonary Fibrosis

Resource links provided by NLM:


Further study details as provided by The Prince Charles Hospital:

Primary Outcome Measures:
  • Number of Participants Who Demonstrated Acute Adverse Events Following Infusion [ Time Frame: 4 hours post-infusion ] [ Designated as safety issue: Yes ]
    Acute adverse events following infusion was defined as the development of anaphalaxis and/or a 25% increase or decrease from baseline of hemodynamic measurements.


Secondary Outcome Measures:
  • Percentage Change in Lung Function as Assessed by FVC Compared to Baseline [ Time Frame: 6 months post MSC infusion ] [ Designated as safety issue: No ]
    Forced Vital Capacity (FVC) was measured and reported as a percentage of predicted and comapred from 6 months post-infusion to baseline

  • Percentage Change in 6 Minute Walk Distance Compared to Baseline [ Time Frame: Baseline and 6 months post MSC infusion ] [ Designated as safety issue: No ]
    At 6 months 6 Minute Walk Distance was mesured and compared as a percentage to baseline

  • Percentage Change in Lung Function as Assessed by DLCO Compared to Baseline [ Time Frame: 6 months post MSC infusion ] [ Designated as safety issue: No ]
    DLCO was measured as a percentage of predicted, and the percentage change between 6 months post-infusion and baseline is reported.


Enrollment: 8
Study Start Date: October 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1*10^6 MSC / kg
Placental MSC
Other: Placental MSC
MSC will be derived from mothers donating their term placenta for clinical trial research purposes at Mater Mothers Hospital, Brisbane. The donation, isolation and expansion of placental-derived MSC for research purposes has been approved by the Mater Health Services (MHS) Human Research Ethics Committee (Reference No. 1292A). These volunteer donor mothers are unrelated to and will be HLA-unmatched with the IPF recipients.
Experimental: 2*10^6 MSC / kg
Placental MSC
Other: Placental MSC
MSC will be derived from mothers donating their term placenta for clinical trial research purposes at Mater Mothers Hospital, Brisbane. The donation, isolation and expansion of placental-derived MSC for research purposes has been approved by the Mater Health Services (MHS) Human Research Ethics Committee (Reference No. 1292A). These volunteer donor mothers are unrelated to and will be HLA-unmatched with the IPF recipients.

Detailed Description:
This is a Phase I, open-label, single centre, non-randomized dose-escalation evaluation of the safety and feasibility of MSC treatment for subjects diagnosed with IPF. The first 4 patients will receive a dose of 1 x 10^6 placenta-derived MSC/kg. An interim safety analysis will be carried out by the Data Safety Management Board (DSMB) when these first 4 patients have all undergone their 3 month study visit. Should no serious adverse events be documented due, or likely due, to the MSC infusion, a subsequent 4 patients will receive an IV infusion of 2 x 10^6 placenta-derived MSC/kg. Therefore a total of up to eight (8) subjects who meet all eligibility criteria and who provide written informed consent will be enrolled in the study.
  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female from 40 to 80 years of age (Note: see exclusion 13 regarding women of child-bearing potential).
  2. Diagnosis of IPF based on the following criteria in accordance with American Thoracic Society/European Respiratory Society (ATS-ERS) guidelines for diagnosing

    IPF:

    Definite or probable usual interstitial pneumonia confirmed on surgical lung biopsy (SLB)

    or

    In absence of SLB, all of the following "major criteria"

    • High resolution CT scan (HRCT) showing definite findings for IPF (bibasilar reticular abnormalities with minimal ground glass opacities)
    • Absence of other causes of IPF including drug toxicities, environmental exposure and connective tissue disease
    • Abnormal pulmonary function tests including evidence of a restrictive ventilatory impairment and impaired gas exchange
    • Transbronchial biopsy or BAL suggesting no features of an alternative diagnosis and three of four of the following "minor criteria"
    • Age greater than 50 years
    • Insidious onset of otherwise unexplained dyspnea on exertion
    • Duration of illness greater than 3 months
    • Bibasal, inspiratory crackles

    Within 90 days of study enrolment, diagnosis must be confirmed by HRCT chest.

  3. Honeycombing greater than 5% in 0 - 3 lung zones (each lung divided into 3 zones - 1) at the level of the carina 2) highest point of right hemi diaphragm and 3) mid way between these two levels) as assessed on HRCT.
  4. 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 0.7 (Pulmonary function tests must be completed no more than 90 days before screening).
  5. Diffusing capacity for carbon monoxide (DLCO) greater than 25% of predicted capacity.
  6. Ability to perform a 6-Minute Walk Test (6MWT) at screening.
  7. Competency to understand the information given in the Human Research and Ethics Committee (HREC) approved ICF and must sign the form prior to the initiation of any study procedures.

Exclusion Criteria:

  1. Diagnosis of an interstitial lung disease (ILD) or restrictive lung disease other than IPF.
  2. Obstructive lung disease as determined by evidence of airflow obstruction on HRCT or physiologic criteria including:

    FEV1/FVC ratio less than 0.7 Residual volume (RV) greater than 120% by plethysmography or significant (verified by radiologist) emphysema on HRCT if plethysmography not available Evidence of reactive airway disease by change in FEV1 of greater than 12% following bronchodilator challenge

  3. 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.
  4. Active or recent (less than 60 days prior to enrolment) significant respiratory tract infection, or a history of frequent (greater than 2 per year for the last 2 years) infective exacerbations of IPF.
  5. Hospitalization within 60 days of screening for an acute exacerbation of IPF (AE-IPF).
  6. Chronic heart failure (NYHA class III/IV) or known left ventricular ejection fraction less than 25%.
  7. Chronic treatment with the following drugs prescribed for IPF (within 4 weeks of randomization):

    oral corticosteroids (greater than 20 mg/day of prednisone or equivalent), immunosuppressive or cytotoxic drugs, antifibrotic drugs, chronic use of N-acetylcysteine

  8. Acute or chronic impairment (other than dyspnea) which limits the ability to comply with study requirements and procedures including the 6MWD
  9. Chronic treatment with immunosuppressive, cytotoxic, or antifibrotic drugs including pirfenidone, D-penicillamine, colchicine, cyclosporine A, TNF-alpha antagonists, imatinib, interferon-gamma, cyclophosphamide, or azathioprine within 30 days of randomization.
  10. Subject requires hemodialysis, peritoneal dialysis or hemofiltration.
  11. Systolic blood pressure less than 85 mmHg.
  12. History of malignancies within the past 5 years, with the exception of squamous or basal cell carcinoma of the skin or successfully treated in situ carcinoma of the cervix.
  13. Female who is of child-bearing potential.
  14. Known history of alcohol abuse within 1 year of enrolment.
  15. Participation in a clinical study involving another investigational drug or device within 28 days of screening.
  16. Co-morbid condition or illness limiting life expectancy to less than 1 year at time of screening.
  17. Serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment or compliance with the protocol.
  18. Significant hypoxemia or hypercapnia at rest on room air as defined by a PaO2 less than 55mmHg or PaCO2 greater than 50mmHg.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385644

Locations
Australia, Queensland
The Prince Charles Hospital
Brisbane, Queensland, Australia, 4032
Sponsors and Collaborators
The Prince Charles Hospital
Mater Medical Research Institute
Investigators
Principal Investigator: Daniel Chambers, MBBS MRCP FRACP MD The Prince Charles Hospital
  More Information

Responsible Party: Daniel Chambers, Dr Daniel Chambers, The Prince Charles Hospital
ClinicalTrials.gov Identifier: NCT01385644     History of Changes
Other Study ID Numbers: HREC/09/QPCH/105 
Study First Received: May 4, 2011
Results First Received: October 20, 2015
Last Updated: November 24, 2015
Health Authority: Australia: Human Research Ethics Committee
Australia: Therapeutic Goods Administration

Keywords provided by The Prince Charles Hospital:
Mesenchymal stem cells
Idiopathic pulmonary fibrosis

Additional relevant MeSH terms:
Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pulmonary Fibrosis
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 29, 2016