Phase IIb Trial to Evaluate Longeveron Mesenchymal Stem Cells to Treat Aging Frailty

• ClinicalTrials.gov Identifier: NCT03169231
• Recruitment Status: Active, not recruiting
• First Posted: May 30, 2017
• Last Update Posted: March 13, 2020
• Sponsor: Longeveron LLC
• Information provided by (Responsible Party): Longeveron LLC

Tracking Information

• First Submitted Date: May 24, 2017
• First Posted Date: May 30, 2017
• Last Update Posted Date: March 13, 2020
• Actual Study Start Date: July 6, 2017
• Estimated Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2017)

Change from baseline in 6 Minute Walk Test (6MWT) compared to placebo [ Time Frame: Baseline and 180 days post-infusion ]

Change from baseline in 6MWT compared to placebo at 180 days post-infusion

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 7, 2019)

• Change in patient reported outcome of overall physical function capacity using the PROMIS-Physical Function-Short Form 20a compared to placebo [ Time Frame: 180 days post-infusion ]
  Change from baseline in physical function will be measured to assess Patient-Reported Outcome Measurement compared to placebo at 180 days post infusion.
• Change in TNF-alpha compared to placebo [ Time Frame: 180 days post-infusion ]
  Change in serum TNF-alpha compared to placebo

Original Secondary Outcome Measures (submitted: May 25, 2017)

• Change in patient reported outcome of overall physical function capacity using the PROMIS-Physical Function-Short Form 20a compared to placebo [ Time Frame: 180 days post-infusion ]
  Change from baseline in physical function will be measured to assess Patient-Reported Outcome Measurement compared to placebo at 180 days post infusion.
• Change in TNF-a compared to placebo [ Time Frame: 180 days post-infusion ]
  Change in serum TNF-a compared to placebo

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase IIb Trial to Evaluate Longeveron Mesenchymal Stem Cells to Treat Aging Frailty
• Official Title: A Phase 2b, Randomized, Blinded and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Longeveron Allogenic Human Mesenchymal Stem Cells Infusion in Patients With Aging Frailty
• Brief Summary: This is a randomized, placebo-controlled, double-blind, parallel arm, multi-center Phase 2b study.
• Detailed Description: The objectives of this study are to assess safety and efficacy of Longeveron Mesenchymal Stem Cells (LMSCs) compared to placebo on 1) functional mobility and exercise tolerance, 2) patient-reported physical function, and 3) the inflammatory cytokine biomarker tumor necrosis factor (TNF-alpha).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Aging Frailty

Intervention

• Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
  Intravenously delivered
• Other: Placebo
  Intravenously delivered

Study Arms

• Experimental: Study Group A
  Single peripheral IV infusion of 25 million Longeveron Mesenchymal Stem Cells (LMSCs)
  Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
• Experimental: Study Group B
  Single peripheral IV infusion of 50 million Longeveron Mesenchymal Stem Cells (LMSCs)
  Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
• Experimental: Study Group C
  Single peripheral IV infusion of 100 million Longeveron Mesenchymal Stem Cells (LMSCs)
  Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
• Experimental: Study Group D
  Single peripheral IV infusion of 200 million Longeveron Mesenchymal Stem Cells (LMSCs)
  Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
• Placebo Comparator: Study Group E
  Single peripheral IV infusion of placebo.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2018): 150
• Original Estimated Enrollment (submitted: May 25, 2017): 120
• Estimated Study Completion Date: July 31, 2021
• Estimated Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent and comply with all procedures required by the Protocol.
2. Be >70 and < 85 years of age at the time of signing the Informed Consent Form.
3. Have a Canadian Study on Health and Aging (CSHA) Clinical Frailty Scale score of 5 "mildly frail" or 6 "moderately frail".
4. Have a 6 minute walk distance of > 200m and < 400 m. Distances of two 6MWTs are to be within 15% of each other.
5. Have a serum TNF-alpha level > 2.5 pg/mL

Exclusion Criteria:

1. Be unwilling or unable to perform any of the assessments required by the protocol.
2. Have a diagnosis of any disabling neurologic disorder, including, but not limited to, Parkinson's disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (e.g., muscle weakness or gait disorder), or diagnosis of dementia.
3. Have a score of 24 or lower on the Mini Mental State Examination (MMSE)
4. Have poorly controlled blood glucose levels (HbA1c >8.0%).
5. Have a clinical history of malignancy within 2.5 years (i.e., subjects with prior malignancy must be cancer free for 2.5 years) except curatively-treated basal cell carcinoma, melanoma in situ or cervical carcinoma.
6. Have any condition that in the opinion of the Principal Investigator limits lifespan to < 1 year.
7. Have autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus).
8. Be using chronic immunosuppressant therapy such as high-dose corticosteroids or TNF-alpha antagonists (prednisone use at doses of < 5 mg daily is allowed).

9. Test positive for hepatitis B virus

   a. If the subject tests positive for anti-hepatitis B core antigen (HBc) or anti-HBs, they must be currently receiving treatment for Hepatitis B prior to infusion and remain on treatment throughout the study.

10. Test positive for verimic Hepatitis C virus, HIV1/2, or syphilis
11. Have a resting blood oxygen saturation of <93% (measured by pulse oximetry).
12. Known or suspected alcohol or drug abuse within three years preceding Screening
13. Have a known hypersensitivity to dimethyl sulfoxide (DMSO).
14. Be an organ transplant recipient (other than transplantation for corneal, bone, skin, ligament, or tendon).
15. Be actively listed (or expected future listing) for transplant of any organ (other than corneal transplant).

16. Have any clinically important abnormal screening laboratory values, including, but not limited to:

    1. Hemoglobin <10.0 g/dL,
    2. White blood cell <2,500/ul, or platelet count <100,000/ul
    3. Liver dysfunction evidenced by enzymes (AST and ALT) > 3 times the upper limit of normal (ULN)
    4. Coagulopathy (INR>1.3) not due to a reversible cause (e.g. warfarin and/or Factor Xa inhibitors).
17. Uncontrolled hypertension (resting systolic blood pressure >180 mm Hg or diastolic blood pressure of > 110 mm Hg at Screening)
18. Have unstable angina pectoris, uncontrolled or severe peripheral artery disease within the previous 3 months.
19. Have congestive heart failure defined by NYHS (New York Heart Association) Class III or IV, or an ejection fraction of <25%.
20. Have a coronary artery bypass surgery, angioplasty, or peripheral vascular disease revasculation or a myocardial infarction within previous 3 months.
21. Have severe pulmonary dysfunction: acute exacerbation of chronic obstructive lung disease stage III or IV (Gold classification), and/or PaO2 levels <60 mmHg.
22. Have a partial ileal gastric bypass, or other significant intestinal malabsorption.
23. Have advanced liver or renal disease
24. Have cognitive or language barriers that prohibit obtaining informed consent or any study elements.
25. Be currently hospitalized, or living in an assisted living facility or a long-term care facility.
26. Be currently participating (or participated within the previous 30 days of consent) in an investigational therapeutic or device trial.
27. Have a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years to 85 Years (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03169231
• Other Study ID Numbers: 001-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Longeveron LLC
• Study Sponsor: Longeveron LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Longeveron LLC
• Verification Date: March 2020