Inclusion Body Myositis Treatment With Celution Processed Adipose Derived Regenerative Cells

Not Applicable

Active, not recruiting

• Conditions: Inclusion Body Myositis
• Interventions: Device: Adipose Derived Regenerative Cells

• Registration Number: NCT04975841
• Lead Sponsor: University of Kansas Medical Center

Brief Summary

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. Stem cell injections will be given in the forearm and thigh on either the left or right side of the body, depending on which side meets criteria. The overall goal of this pilot study is to test the safety of adipose derived regenerative cells in patients with Inclusion Body Myositis. If determined safe, this trial could lead to larger Phase II trials. While this specific trial's primary endpoint is safety, it our ultimate hope that ADRC injections into the forearm and thigh of IBM patients will slow, stabilize, or even reverse the progression of muscle weakness in patients with IBM.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-11-09
• Study First Submitted QC: 2021-07-20
• Study First Posted: 2021-07-23
• Study Start: 2022-03-10
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-12
• Last Update Posted: 2022-10-14
• Primary Completion: 2025-11-01
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM. (see Appendix 3)
2. Demonstrate being able to arise from a chair without support from another person or device. Subjects may use their arms to push up.
3. 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.
4. Age at onset of weakness > 45 years
5. Able to give informed consent
6. 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

1. 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.

2. 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

3. History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM.

4. History of non-compliance with other therapies.

5. Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency.

6. Coexistence of any other neurological, cardiac, pulmonary, psychiatric, or rheumatologic disease that would likely to affect outcome measures.

7. 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.

8. Use of cannabis

9. 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.

10. 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).

11. 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.

12. Patients who have aPTT (Activated Partial Thromboplastin Time) values ≥ 1.8 X the normal value.

13. Patients who have received any anticoagulant within 1 hour prior to liposuction.

14. Patients who have received any anticoagulant within 1 hour of stem cell procedure

15. Patients who are on substantial anticoagulation (eg: GIIb/IIIa inhibitor class drugs) who cannot stop it within two weeks prior to adipose harvest

16. Participants who's IBM age of onset is under of 45

17. Participants with an elevated alkaline phosphatase level which may indicate Paget disease

18. Participants allergic or sensitive to lidocaine and or epinephrine

19. 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

20. Use of other concomitant myositis treatment drugs, or cell or gene therapies (e.g. Arimoclomol, Bimagrumab, Follistatin, Rapamycin)

21. Any patient with an area of active skin infection at the site of lipoharvest

22. Participants that are current smokers, defined as an adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Stem Cell Injection	Adipose Derived Regenerative Cells	Stem Cell Injection: The three subjects randomized to early injections will proceed directly to Part 2 with staggered enrollment of 1 subject every 3 months. Once the safety data of the first subject at Month 3 is assessed, the second subject will be enrolled. Once the safety data of the first 2 subject (Subject 1 at Month 6 and Subject 2 at Month 3) are assessed, the third early injection subject will be enrolled in Part 2.

Primary Outcome Measures

Name	Time	Method
Safety (Frequency and Severity of Adverse Events)	3 months post treatment	The primary endpoint of safety will be reported as counts of subjects experiencing adverse events events (including abnormal laboratory results and vital signs). Six months after the first participant is treated, safety and efficacy will be accessed in order to make a decision about whether to continue the trial. Measures of safety will be reported for the last visit observed for each participant

Secondary Outcome Measures

Name	Time	Method
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) from Baseline	6 months post treatment	The IBMFRS is a quickly administered (10-minute) ordinal rating scale used to determine participants' assessment of their capability and independence. It includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40, with a higher score representing less functional limitation.
Change in Modified Timed Up and Go (mTUG) from Baseline	6 months post treatment	We will measure the patient's ability to get up from a chair allowing participants to use their arms (since most with sIBM cannot perform the task without pushing off), walk 3 meters, turn around and walk back to the chair and sit down. The use of nearby walls, or assistance from a caregiver is not allowed. This test will be performed twice and the fastest time will be used in the data analysis.
Change in Grip Strength from Baseline	6 months post treatment	Grip strength is done with the use of a Martin Vigorimeter that will measure grip strength. The maximum force generated by the patient from the two trials is used for each muscle group.
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from Baseline	6 months post treatment	This is a self-report functional status measure based on the patient-centered dimension of disability.
Change in Patient Global Impression of Change from Baseline	6 months post treatment	The Patient Global Impression of Change (PGIC) is an assessment by the subject of self-perceived change in ability to conduct daily activities since the start of study medication. The scale ranges from 'very much worse' to 'much worse,' 'a little worse,' 'no change,' 'a little improved,' 'much improved,' and 'very much improved'.
Change in Manual Muscle Testing (MMT) from Baseline	3, 6, and 12 months post treatment	Manual muscle testing occurs when the evaluator records strength by having the subject resist while pushing on certain muscle groups with their arms and hands. MMT will include bilateral Knee Extension and Finger Flexion on the Kendall modification of the MRC scale being 0-10 scale.
Change in Handheld Dynamometry (HHD) from Baseline	6 months post treatment	HHD will be done using a MicroFET2 hand myometer. This is a hand-held device that allows the examiner to push against a muscle while the patient resists. Unlike the manual muscle test which provides a range, this device will provide an actual number. Knee extension will be tested bilaterally.

Trial Locations

Locations (1)

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States