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

NCT01385644 | Completed Phase 1 Results DMC

• 1 other identifier: HREC/09/QPCH/105
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Mesenchymal stem cells; Idiopathic pulmonary fibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Demonstrated Acute Adverse Events Following Infusion

  Acute adverse events following infusion was defined as the development of anaphalaxis and/or a 25% increase or decrease from baseline of hemodynamic measurements.

  4 hours post-infusion

Secondary Outcomes (3)

• Percentage Change in Lung Function as Assessed by FVC Compared to Baseline

  6 months post MSC infusion

• Percentage Change in 6 Minute Walk Distance Compared to Baseline

  Baseline and 6 months post MSC infusion

• Percentage Change in Lung Function as Assessed by DLCO Compared to Baseline

  6 months post MSC infusion

Study Arms (2)

1*10^6 MSC / kg

EXPERIMENTAL

Placental MSC

Other: Placental MSC

2*10^6 MSC / kg

EXPERIMENTAL

Placental MSC

Other: Placental MSC

Interventions

Placental MSC OTHER

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.

1*10^6 MSC / kg; 2*10^6 MSC / kg

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.
• 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.
• 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).

You may not qualify if:

• 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 0.7 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
• 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 enrolment) significant respiratory tract infection, 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 25%.
• 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
• Acute or chronic impairment (other than dyspnea) which limits the ability to comply with study requirements and procedures including the 6MWD
• 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.
• Subject requires hemodialysis, peritoneal dialysis or hemofiltration.
• Systolic blood pressure less than 85 mmHg.
• 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.
• Female who is of child-bearing potential.

Sponsors & Collaborators

• The Prince Charles Hospital: lead
• Mater Medical Research Institute: collaborator

Study Sites (1)

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Assoc Professor Daniel Chambers
• Organization: The Prince Chalres Hospital

daniel.chambers@health.qld.gov.au

+61 7 3139 4000

Study Officials

• Daniel Chambers, MBBS MRCP FRACP MD

  The Prince Charles Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Daniel Chambers

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: June 30, 2011
• Study Start: October 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: December 29, 2015
• Results First Posted: December 29, 2015

Record last verified: 2015-11

Locations

AU (1)