Allogeneic Human Cells (hMSC) Via Intravenous Delivery in Patients With Mild Asthma

Phase 1

Terminated

• Conditions: Asthma
• Interventions: Biological: hMSCs

• Registration Number: NCT03137199
• Lead Sponsor: Marilyn Glassberg

Brief Summary

A Phase 1 investigation will be performed to test the safety of two doses of bone marrow-derived MSCs (20,000,000 and 100,000,000) administered via peripheral intravenous infusion.

Detailed Description

A Phase 1 investigation will be performed to test the safety of two doses of bone marrow-derived MSCs (20,000,000 and 100,000,000) administered via peripheralintravenous infusion.

Group 1: 3 subjects will receive a single administration of allogeneic hMSCs: 20 million cells delivered via peripheral intravenous infusion Group 2: 3 subjects will receive a single administration of allogeneic hMSCs: 100 million cells delivered via peripheral intravenous infusion Interim safety analysis will be performed four weeks after the 1st subject is enrolled in each cohort. Continued safety and tolerability with review of adverse events (AEs) will be assessed at each visit. Efficacy parameters (pulmonary function tests, diffusing capacity (DLCO), lung volumes, 6-minute walk test (6MWT), and dyspnea/quality of life \[QOL\] questionnaires) will be assessed every 12 weeks until study completion. Clinical laboratory tests to assess safety will be performed at every visit.

Study Timeline

• Study First Submitted: 2017-04-24
• Study First Submitted QC: 2017-04-29
• Study First Posted: 2017-05-02
• Study Start: 2017-06-22
• Primary Completion: 2020-03-03
• Study Completion: 2020-04-29
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-20
• Last Update Posted: 2020-05-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• Provide written informed consent
• be between 18 and 65 years at the time of signing the Informed Consent
• have a clinical diagnosis of asthma prior to screening in accordance with the guidelines of the American Thoracic Society/European Respiratory Society
• ACQ over 1.25
• have a smoking history of less than 10 pack-years total and have not been smoking for at least the last 12 months
• Perform a positive methacholine challenge at screening and repeat positive methacholine challenge at baseline visit (14 days later)
• Have normal or mild obstructive spirometry
• Have normal right heart function as documented by Doppler echo or right heart catheterization
• If female, be surgically sterile, post-menopausal (more than 1 year), or practice double barrier methods of birth control
• Subjects may receive non-drug therapies including oxygen supplementation no greater than 2L/minute, and pulmonary rehabilitation
• Subjects may be on standard of care asthma medications including inhaled corticosteroids-long acting beta agonist at a dose not greater than 1 mg of a fluticasone equivalent

Exclusion Criteria

• Have any active infection that is not treated
• Be unable to perform any of the assessments required for endpoint analysis.
• currently receive (or have received within four weeks of screening) experimental agents for the treatment of asthma
• be actively listed (or expecting to be listed in the near future) for transplant of any organ
• Have clinically important abnormal screening laboratory values : blood screening tests (Hematology, Chemistry, CBC including Eosinophil count) results that are not within normal limits (according to UMHC Laboratory Reference Ranges) Have a 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
• 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
• Have a non-pulmonary condition that limits lifespan to less than a year.
• Have a history of drug or alcohol abuse within the past 24 months.
• Be serum positive for HIV, hepatitis BsAg or Viremia hepatitis C
• Be currently participating (or have participated within the previous 30 days) in an investigational therapeutic or device trial.
• Have hypersensitivity to dimethyl sulfoxide (DMSO)
• Have a resting oxygen saturation (SpO2) on room air of more than 93% at sea level or more than 88% at an altitude above 5,000 feet above sea level (1524 meters)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group receiving 20 million hMSCs	hMSCs	3 patients will receive a single administration of allogeneic hMSCs: 20 x106 (20 million) cells delivered via peripheral intravenous infusion
Group receiving 100 million hMSCs	hMSCs	3 patients will receive a single administration of allogeneic hMSCs: 1 x108 (100 million) cells delivered via peripheral intravenous infusion

Primary Outcome Measures

Name	Time	Method
Number of Participant with treatment emergent serious adverse events	Week 4 post infusion	as defined as the incidence of any treatment-emergent serious adverse events; these are a composite of death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities

Secondary Outcome Measures

Name	Time	Method
Difference in subject reported dyspnea and quality of life assessments	Participants will be followed from 1 week to an expected average of 48 weeks following infusion	Difference in subject reported dyspnea and quality of life assessments: Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ)
Death from any cause	Participants will be followed from 1 week to an expected average of 48 weeks following infusion	Death from any cause
Difference in lung function	Participants will be followed from 1 week to an expected average of 48 weeks following infusion	Difference in FEV1 Variability in morning peak expiratory flow measurements; Difference in frequency of acute exacerbations defined as: hospitalizations, missed work days, and/or oral steroids for more than 3 days Decrease in fractional excretion of inhaled NO (FENO; less than 50 ppb)
Decrease in peripheral eosinophilia	Participants will be followed from 1 week to an expected average of 48 weeks following infusion	Decrease in number of peripheral eosinophils

Trial Locations

Locations (1)

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States