Inclusion Body Myositis Treatment With Celution Processed Adipose Derived Regenerative Cells

Inclusion Body Myositis (IBM) is the most common progressive and debilitating muscle disease beginning in persons over age 50 years, with an annual incidence estimated at 2.2 to 7.9 per million. IBM causes both proximal and distal muscle weakness, characteristically most prominent in the quadriceps and finger flexors. Over time it can lead to severe disability, including loss of hand function, falls due to quadriceps muscle weakness and foot drop, dysphagia, and eventually respiratory muscle weakness. There is no effective therapy for IBM.

This study, "Inclusion Body Myositis Treatment with Celution Processed Adipose Derived Regenerative Cells" (IBM-ADRC) evaluates the safety and efficacy of the Celution System in the processing of an autologous graft consisting of adipose-derived regenerative cells (ADRCs) in the treatment of inclusion body myositis. Specifically, the overall objective is for the proposed clinical trial to serve as a safety trial for Inclusion Body Myositis.

This is an open-label, single arm study evaluating the safety for patients with Inclusion Body Myositis. A total of 9 subjects will be enrolled in the study. Subjects will be randomized to Part 1 or Part 2 of the study in blocks of 3 every 3 months.

Enrollment is anticipated to be staggered into 3 groups. The nine subjects will be randomized 2:1 in groups of 3 to early injections (Part 2) versus late (Part 1).

Stem cell injections will occur unilaterally in the flexor digitorum profundus muscles and the quadriceps group of muscles.

Inclusion criteria

• Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM. (see Appendix 3)
• Demonstrate being able to arise from a chair without support from another person or device. Subjects may use their arms to push up.
• Able to ambulate at least 20 ft/6 meters with or without assistive device. Once arisen from the chair, participant may use any walking device, i.e. walker/frame, cane, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support.
• Age at onset of weakness > 45 years
• Able to give informed consent
• Muscle strength graded between 6 and 9 for finger flexion and knee extension unilaterally on one side of the body (right or left) using the Kandell 0-10 scale. A subject may meet this criterion bilaterally and still be included in the study.

Exclusion criteria

• History of any of the following excludes subject participation in the study: chronic infection particularly HIV or Hepatitis B or C; cancer other than basal cell cancer less than five years prior, or other chronic serious medical illnesses.
• Presence of any of the following on routine blood screening: WBC < 3000; platelets < 100,000; hematocrit < 30%; BUN > 30 mg/dL; creatinine > 1.5 x upper limit of normal; symptomatic liver disease with serum albumin < 3 g/dl
• History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM.
• History of non-compliance with other therapies.
• Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency.
• Coexistence of any other neurological, cardiac, pulmonary, psychiatric, or rheumatologic disease that would likely to affect outcome measures.
• Drug or alcohol abuse within past three months. Patient has recent history (within 6 months before Screening) of chronic alcohol or drug abuse which may compromise the patient's safety or ability to participate in study activities.
• Use of cannabis
• Participation in a recent drug study in the last 30 days prior to the screening visit or use of biologic agents less than 6 months prior to the screening visit.
• Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for both male and female participants until 4 weeks after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication. Acceptable methods of birth control are:

i. Hormonal methods associated with inhibition of ovulation such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before IMP administration.

ii. Total abstinence from sexual intercourse since the last menses before IMP administration. (The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), are not acceptable methods of contraception).

iii. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). If the subject is a sexually active male with female partners of child-bearing potential (postmenarchal)* he must use a condom with or without spermicide in addition to the birth control used by his partners during the trial until 3 months after the last dose of trial medication. *Non child-bearing potential is defined as post-menopausal (minimum of 12 months with no menses and follicle-stimulating hormone in the post-menopausal range) or sterilisation (hysterectomy, oophorectomy, or bilateral tubal ligation).

• Participants taking corticosteroids within the previous 30 days prior to screening. Participants on intravenous immunoglobulin (IVIg) or other immunosuppressants within the last 3 months. Topical, nasal, and ocular corticosteroids are allowed unless they are being widely applied or the severity of the underlying condition makes them unsuitable in the Investigator's opinion. Local steroid injections are allowed.
• Patients who have aPTT (Activated Partial Thromboplastin Time) values ≥ 1.8 X the normal value.
• Patients who have received any anticoagulant within 1 hour prior to liposuction.
• Patients who have received any anticoagulant within 1 hour of stem cell procedure
• Patients who are on substantial anticoagulation (eg: GIIb/IIIa inhibitor class drugs) who cannot stop it within two weeks prior to adipose harvest
• Participants who's IBM age of onset is under of 45
• Participants with an elevated alkaline phosphatase level which may indicate Paget disease
• Participants allergic or sensitive to lidocaine and or epinephrine
• Participants with known drug exposures associated with neuromuscular side effects including antimalarial drugs (eg, chloroquine, hydroxychloroquine), colchicine, glucocorticoids, cholesterol-lowering drugs (eg, HMG-CoA reductase inhibitors [statins]) except if on stable dose for more than a year without impact on IBM progression, alcohol abuse, and cocaine
• Use of other concomitant myositis treatment drugs, or cell or gene therapies (e.g. Arimoclomol, Bimagrumab, Follistatin, Rapamycin)
• Any patient with an area of active skin infection at the site of lipoharvest
• Participants that are current smokers, defined as an adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.