The project is described as a Phase 1 Clinical Safety Study intended to providepreliminary assessments of the safety, tolerability, and secondarily to be vigilant forsignals of amelioration of symptoms associated with Post-Acute Sequelae of SARS-CoV-2infection
The proposed study is a randomized single-center, double-blinded, placebo controlled
standard of care plus study. Each participant will continue to receive standard of care
treatment for their current diagnosis and be afforded the opportunity to add any
additional care as needed that may include care for behavioral health concerns. In the
proposed study, safety of a single administration of expanded autologous lines at a total
dose exposure of 150 million cells ("ATCell™") will be assessed. Each ATCell™ cell batch
will be derived from ex vivo expanded stromal vascular fraction (SVF) of a participant's
own adipose tissue. SVF is collected by liposuction and expanded. Briefly, ATCell
suspended in Lactated Ringer's with 5% dextrose solution, or a placebo of Lactated
Ringers 5% dextrose solution will be administered once to each participant. Safety will
be evaluated through clinical assessments and laboratory test results comparing treatment
cohort participant's baseline assessments and laboratory test results. Following
completion of follow up period as defined in the schedule of events, the study will be
unblinded, the results reviewed by the Institutional Review Board (IRB) and Human
Research Protection Program (HRPP). Once safety has been reviewed by IRB/ HRPP, the study
will be unblinded and participants that received the placebo treatment will be offered
the opportunity to crossover and receive 150 million cell ATCell™ autologous treatment
with the same monitoring and clinical support afforded to the first treatment cohort.
Procedure: Adipose Tissue Harvest
Local Anesthesia will be administered. A Stab wound will be created at the harvest site
through which a 3.0 or 2.5 mm cannula will be inserted to suction fat using the "syringe"
(i.e. manual) technique. A total of 100 cc of lipoaspirate will be collected by manual
draw of the adipose tissue into syringes.
Other Name: Liposuction
Biological: ATCell
Infusion of the study medication at the rate of 575 mL/HR (500ml of LRD5 plus 75ml of
ATCell suspended in LRD5) and continue until all received trial medication has been
delivered.
Other Name: Autologous Adipose Derived Mesenchymal Stem Cells
Inclusion Criteria:
1. Active duty service members: military retirees, DEERS eligible dependents who are
Tricare beneficiaries only (Department of Defense (DoD) investigational sites only)
2. Participants ages of 18 years and above
3. Documentation of a positive COVID-19 polymerase chain reaction (PCR) test or strong
history of SARS-CoV-2 exposure with positive supportive serology
4. Male or female or other gender
5. Individuals with established diagnosis of PASC
6. Subjects with moderate to severe levels of PASC based on synthesis of multiple
assessment modalities provided by the multispecialty study team.
7. PASC phenotype to include signs and symptoms of fatigue and low endurance and either
Autonomic Disorder or Dyspnea or both.
8. Subjects who are able to comprehend the consent procedure and follow the treatment
process.
9. Female participants of childbearing potential and at risk of pregnancy during the
study must agree to use 2 highly effective methods of contraception throughout the
study and for 112 days after the last study visit.
10. Female participant who are not of childbearing potential (i.e,. must meet at least
one (1) of the following criteria): have undergone a hysterectomy and/or bilateral
oophorectomy, or ovarian failure .
11. For male subjects who can father a child and are having intercourse with females of
childbearing potential who are not using adequate contraception, willingness to use
a barrier method of contraception (condom) from the start of study therapy until ≥
90 days after the end of the study and to refrain from sperm donation until ≥ 90
days after the end of the study.
12. Achieved postmenopausal status defined as follows: cessation of regular menses for
at least 12 consecutive months with no alternative pathological or psychological
cause and have a serum follicle stimulating hormone (FSH) level confirming the
post-menopausal state.
13. Individuals who are willing and able to comply with lifestyle guidelines, scheduled
visits, treatment plan, laboratory tests, and other study procedures through the end
of the final study visit.
14. Individuals with the following Vital Signs:
1. Systolic Blood Pressure of > 100 or < 140 (mmHg)
2. Diastolic Blood Pressure of > 60 or <90 (mmHg)
3. Heart Rate of > 60 or < 100 (bpm) (beats per minute)
4. Temperature of < 38°C (afebrile)
5. Respiratory Rate of > 12 or < 20 (bpm) (breaths per minute)
6. Pulse Ox greater than >95% on room air
7. BMI < 28
Exclusion Criteria:
5.3.7.4 Exclusion Criteria:
1. Subjects with documented past or current history of severe depression, suicidal
ideations or suicidal attempts.
2. Subjects who are unable to comprehend the content of informed consent
3. Female subjects who are pregnant or who are not willing to practice effective
contraception during and for 112 days following the last study visit
4. Female subjects who are breastfeeding
5. History of abnormal brain or spinal MRI for presence of thromboembolic events.
6. Recent traumatic brain injury or other concussive event within 12 months of medical
history review
7. History of abnormal Echocardiogram for cardiac structure or function in the last 10
years.
8. Prior history of postural orthostatic tachycardia syndrome predating diagnosis of
SARS-CoV2 infection
9. Uncontrolled hypertension or hyperlipidemia
10. Prior to COVID diagnosis, the presence of abnormal chest x-ray for any parenchymal
disease, or,
1. Active tuberculosis or ongoing treatment for tuberculosis or any acute or
chronic infection affecting lung
2. Chronic lung disease due to fibrosis or autoimmune inflammation such as
sarcoidosis or rheumatoid arthritis, vasculitis or lupus
3. Lung cancer
4. Asthma
5. Chronic obstructive pulmonary disease (COPD)
6. Emphysema
7. Disorders of upper airway, larynx, or trachea that pose potential complications
in a state of emergency for airway management due to SAE.
8. Disorders of pleura that affects pulmonary functions
11. Prior history of connective tissue diseases
12. History of severe hospitalization from COVID-19 or other respiratory infection
requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
13. Pulse oxygenation readings <95% on room air during screening exam
14. History of pulmonary embolism during lifetime
15. Prior history of deep venous thromboses, stroke or myocardial infarction
16. Any thrombophilia, including factor V Leiden, protein C deficiency, and protein S
deficiency
17. Ongoing pharmaceutical or radiation treatment for infection or malignancy
18. Prior positive test for any of the following without demonstration of resolution:
viral Hepatitis B or C (HBV, HCV), Human Immunodeficiency virus -1 or -2 (HIV1 or
HIV2), Human T cell leukemia virus -I or -II (HTLV-1 or HTLV-II), West Nile, Zika,
Syphilis.
19. Use of any immunosuppressive, immune modulating drugs include calcineurin
inhibitors, antimetabolites, alkylating agents, for greater than 14 consecutive days
over the last 3 months
20. Actively listing (or expected listing) for transplant of any organ, other than
corneal, bone, skin, ligament or tendon transplant.
21. Be an organ transplant recipient in the past, other than for corneal, bone, skin,
ligament or tendon transplant.
22. History of malignant tumor within the past 10 years for breast cancer and 5 years
for all other cancers.
23. Individuals allergic to local anesthetics
24. Individuals with inadequate subcutaneous tissue to allow appropriate lipoaspirate
(i.e., fat extraction)
25. Any history of autoimmune illnesses including but not limited to: Multiple
sclerosis, Crohn's disease, Myasthenia gravis, Hashimoto's thyroiditis, psoriatic
arthritis, Pernicious anemia/atrophic gastritis, Guillain-Barre, Chronic
inflammatory demyelinating polyneuropathy, Type 1 diabetes mellitus, Inflammatory
bowel disease, Systemic lupus erythematosus, vasculitis, Immune thrombocytopenic
purpura, inflammatory muscle disease or Rheumatoid arthritis, Rheumatic fever.
26. Uncontrolled type 2 diabetes
27. Any abnormal test result, in the opinion of the PI and the study team, that may
compromise the safety or compliance of the participant or preclude successful
completion of the study, or that may compromise the validity of the study.
28. Individuals expecting retirement, military separation, deployment or relocation in
the next 12 months.
Not Provided
Anthony Dudzinski
1-732-747-1007
tdudzinski@americancryostem.com
Anthony Y Dudzinski, Study Director
American CryoStem Corporation