Allogeneic Human Cells (hMSC)in Patients With Idiopathic Pulmonary Fibrosis Via Intravenous Delivery (AETHER)

NCT02013700 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20120946
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, randomized, blinded, placebo-controlled 9 subjects pilot safety run-in followed by an additional 16 randomized subjects for a total of 25 subjects. In the pilot phase subjects will be randomized into three treatment groups of allogenic mesenchymal stem cells and in the randomized phase subjects will receive either allogenic mesenchymal stem cells or matched placebo.

Conditions

Idiopathic Pulmonary Fibrosis (IPF)

Keywords

IPF; Pulmonary fibrosis

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of intravenous allo hMSCs in patients with Idiopathic Pulmonary Fibrosis (IPF).

  Safety (Primary): Incidence (one month post infusion) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.

  One month post infusion

Secondary Outcomes (5)

• - To explore effects of allo hMSCs on lung function: forced vital capacity (FVC).

  Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.

• To explore effects of allogenic human mesenchymal stem cells on symptom related quality of life.

  Participants will be followed from 4 weeks to an expected average of 60 weeks following infusion.

• Difference in frequency of acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF)

  4 weeks following infusion

• Death from any cause.

  60 weeks.

• To explore effects of allogenic human mesenchymal stem cells on lung function: Diffusing Capacity (DLCO)

  Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.

Study Arms (4)

20 million hMSCs

EXPERIMENTAL

Patients will receive a single administration of Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs): 2 x10\^6 (20 million) cells delivered via peripheral intravenous infusion

Biological: Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs)

Placebo

PLACEBO COMPARATOR

Patients will receive a matched placebo delivered via peripheral intravenous infusion

Biological: matched placebo

100 million hMSCs

EXPERIMENTAL

Patients will receive a single administration of Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs): 100 x10\^6 (20 million) cells delivered via peripheral intravenous infusion

Biological: Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs)

200 million hMSCs

EXPERIMENTAL

Patients will receive a single administration of Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs): 200 x10\^6 (200 million) cells delivered via peripheral intravenous infusion

Biological: Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs)

Interventions

Allogeneic Adult Human Mesenchymal Stem Cells (hMSCs) BIOLOGICAL

100 million hMSCs; 20 million hMSCs; 200 million hMSCs

matched placebo BIOLOGICAL

The placebo will be 25 ml of Plasma-Lyte A with 1% HSA in a Cryostore bag.

Placebo

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent.
• Subjects age equal to or greater than 40 and equal to or less than 90 years at the time of signing the Informed Consent Form.
• Have a clinical diagnosis of Idiopathic Pulmonary Fibrosis (IPF) prior to screening
• Forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity (DLCO) ≥30% (corrected for hemoglobin but not alveolar volume).
• RVSP equal to or less than 50 mmHg, as documented by Doppler echo or right heart catheterization.
• Female subjects must be surgically sterile or post-menopausal (greater than 1 year).

You may not qualify if:

• HRCT and/or surgical lung biopsy results inconsistent with the diagnosis of IPF.
• Infiltrative lung disease of any type other than Idiopathic Pulmonary Fibrosis (IPF), lungs disease related to fibrogenic agents, toxins, drugs or other exposures, granulomatous lung disease, pulmonary vascular disease, or known connective tissue disease.
• Inability to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform pulmonary function tests or high resolution CT (HRCT), undergo blood draws, read and respond to questionnaires.
• Currently receiving (or received within four weeks of screening) any medication, treatment, or experimental agents for the treatment of Idiopathic Pulmonary Fibrosis (IPF), except for patients receiving non drug therapies will include oxygen saturation therapy (oxygen supplementation) and pulmonary rehabilitation.
• Active listing (or expected future listing) for transplant of any organ.
• Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin \<8 g/dl, white blood cell count \<3000/mm3, platelets \<80,000/mm3, INR \> 1.5, aspartate transaminase, alanine transaminase, or alkaline phosphatase \> 3 times upper limit of normal, total bilirubin \> 1.5 mg/dl.
• Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to: HIV, advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilatory defect.
• Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
• Have known allergies to penicillin or streptomycin.
• Be an organ transplant recipient.
• Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively- treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
• Have a non-pulmonary condition that limits lifespan to less than 1 year.
• Have a history of drug or alcohol abuse within the past 24 months.
• Be serum positive for Human immunodeficiency virus (HIV), hepatitis BsAg or Viremic hepatitis C.
• Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.

Sponsors & Collaborators

• Joshua M Hare: lead
• The Lester And Sue Smith Foundation: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (1)

Interdisciplinary Stem Cell Institute / University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Glassberg MK, Minkiewicz J, Toonkel RL, Simonet ES, Rubio GA, DiFede D, Shafazand S, Khan A, Pujol MV, LaRussa VF, Lancaster LH, Rosen GD, Fishman J, Mageto YN, Mendizabal A, Hare JM. Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. Chest. 2017 May;151(5):971-981. doi: 10.1016/j.chest.2016.10.061. Epub 2016 Nov 24.

  PMID: 27890713 BACKGROUND

Related Links

• Interdisciplinary Stem Cell Institute University of Miami

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marilyn K. Glassberg, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Science Officer / Director of Interdisciplinary Stem Cell Institute

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 17, 2013
• Study Start: November 13, 2013
• Primary Completion: December 11, 2015
• Study Completion: November 24, 2016
• Last Updated: March 9, 2021

Record last verified: 2021-03

Locations

US (1)