Safety and Tolerability of IMMUNA(IMM01-STEM) in Patients With Muscle Atrophy Related to Knee Osteoarthritis.

Study Overview
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Brief Summary
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An open-label dose escalation study to assess the safety and tolerability of IMMUNA(IMM01-STEM) in participants with muscle atrophy related to knee osteoarthritis

Detailed Description
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This will be an open-label, dose escalation study to assess the safety and tolerability of IMMUNA(IMM01-STEM), a secretome product derived from partially differentiated pluripotent stem cells that contains regenerative molecules, in participants with muscle atrophy related to knee osteoarthritis (KOA). Up to 18 participants will receive twice weekly intramuscular administration of IMMUNA(IMM01-STEM) for 4 weeks in up to 3 dose cohorts: Cohort A, IMMUNA 225μg; Cohort B, IMMUNA 450 μg; and Cohort C, IMMUNA 900 μg. Study participants will sign a written Informed Consent Form (ICF) prior to the conduct of any study related procedures. A study participant who provides written informed consent will be screened within 28 days prior to treatment. Screening assessments will be conducted, after which the study participants' eligibility will be determined on the basis of the inclusion and exclusion criteria. Eligible participants will be enrolled and undergo Baseline assessments on Day 1. Patients will receive IMM01-STEM twice a week for 4 weeks, for a total of 8 injections. Site staff will administer study medication by im injection using a small-gauge needle (eg, 24 or 26 Ga) at all scheduled visits. After each administration of study medication, participants will be observed for 3 hours to monitor for injection-related reactions and other early onset treatment-related adverse events (AEs), in particular for the presence of allergic reactions. After Visit 2 and 3, there will be follow-up phone contact 6 to 8 hours later the same day and once the day following each injection. After their last injection, participants will enter a Safety Follow-Up (SFU) period, with clinic visits 3 days after their last injection and then monthly for 3 months.

Official Title
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An Open-label Dose Escalation Study to Assess the Safety and Tolerability of IMM01-STEM in Participants With Muscle Atrophy Related to Knee Osteoarthritis

Conditions
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Muscle Atrophy

Intervention / Treatment
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* Drug: IMM01-STEM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has moderate KOA (defined as Kellgren-Lawrence [KL] grade 2 to 3) on affected limb Has quadriceps weakness (<7.5N/kg) Can ambulate >50 feet unassisted Must have negative laboratory test results for human immunodeficiency virus, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) at the Screening Visit Has a body mass index (BMI) of <40kg/m2 A male must agree to use contraception during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period. A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP). OR A WOCBP who agrees to follow the protocol's contraceptive guidance during the treatment period and for at least 3 months after the last dose of study treatment. Female has a negative pregnancy test result at screening and prior to investigational medicinal product (IMP) administration Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol Willing and able to comply with all study requirements, according to the judgment of the Investigator Has discontinued systemic oral or intravenous steroid use for 6 months prior to Screening Has vital sign measurements within the following ranges at Baseline (predose at Visit 2): heart rate >50 and <100 bpm, systolic blood pressure >100 and <170 mmHg, diastolic blood pressure >50 and <90 mmHg, and blood oxygenation (by pulse-oximetry) >95% Participant has undergone and failed at least 1 3-month or longer treatment regimen (ie, activity modification, weight loss, physical therapy, anti-inflammatory medications, or injection therapy) within a 2-year period prior to the Screening visit. Study participant is able to speak, read, and understand English, in order to understand the nature of this study. Exclusion Criteria: Moderate to severe KOA (defined as KL grade >3) on contralateral limb Has had prior total knee arthroplasty Has a known hypersensitivity to any components of the study medication or comparative drugs (and/or an investigational device) as stated in this protocol Has current or past history of malignancy (10y) excluding nonmelanoma skin cancer Has neurological, vascular, or cardiac condition that limit function, or, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study Has uncontrolled comorbidities including diabetes (hemoglobin A1c level >7.0%), Hypertension (resting heart rate >100 bpm, systolic blood pressure >170 mmHg, or diastolic blood pressure >90 mmHg), cardiovascular disease, asthma, or COPD. Is taking a prohibited medication or has taken a prohibited medication (narcotic pain medication, local anti-inflammatory, other investigational drugs) Participant has had a change in medication to manage comorbid condition(s) (including diabestes, hypertension, asthma, and cardiovascular disease) within 1 month of the Screening visit. Participant received intra-articular cortisone or viscosupplementation product(eg, Synvisc®) injections within 3 months prior to the first dose of IMP. Has had administration of a live, attenuated vaccine within 28 days of starting study treatment or anticipation that such vaccine will be required during the study Prior/concurrent clinical study experience Has current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) Has a positive urine drug screen (with the exception of benzodiazepine) prior to dosing on Day 1. If a study participant presents with a positive drug screen, the participant may be rescheduled at the discretion of an Investigator. Has the presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb) test result at Screening or within 3 months prior to starting study medication Tests positive for human immunodeficiency virus-1/2 antibody (human immunovirus 1/2Ab) at Screening or within 3 months prior to the first dose of study medication Has current or past history (10y) of smoking Has a history of chronic alcohol or drug abuse within the previous 3 months Participant is currently using a systemic oral or intravenous steroid regimen (eg, for asthma or other chronic respiratory condition) or brief course of systemic pulse steroid administration (eg, for flare up of nonarthritic condition or COVID-19).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3 dose cohorts: Cohort A, IMMUNA(IMM01-STEM) 225μg; Cohort B, IMMUNA(IMM01-STEM) 450 μg; and Cohort C, IMMUNA(IMM01-STEM) 900 μg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort A<br>Participants will receive twice weekly intramuscular (im) administration of IMMUNA(IMM01-STEM) for 4 weeks with a dose of 225μg. | Drug: IMM01-STEM<br>* IMMUNA (IMM01-STEM) is a secretome product derived from partially differentiated pluripotent stem cells that contains regenerative molecules.<br>* Other names: IMMUNA;|
| Active Comparator: Cohort B<br>Participants will receive twice weekly intramuscular (im) administration of IMMUNA(IMM01-STEM) for 4 weeks with a dose of 450μg. | Drug: IMM01-STEM<br>* IMMUNA (IMM01-STEM) is a secretome product derived from partially differentiated pluripotent stem cells that contains regenerative molecules.<br>* Other names: IMMUNA;|
| Active Comparator: Cohort C<br>Participants will receive twice weekly intramuscular (im) administration of IMMUNA(IMM01-STEM) for 4 weeks with a dose of 900μg. | Drug: IMM01-STEM<br>* IMMUNA (IMM01-STEM) is a secretome product derived from partially differentiated pluripotent stem cells that contains regenerative molecules.<br>* Other names: IMMUNA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of IMMUNA(IMM01-STEM) treatment in study participants with muscle atrophy related to KOA | Determined by the incidence and severity of dose-limiting toxicities (DLTs) and the incidence of treatment-emergent adverse events (TEAEs). Adverse events (AE) are classified based on Common Terminology Criteria for Adverse Events (CTCAE) as follows: Grade 0 = no adverse events, Grade 1= mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = fatal adverse events. A DLT is defined as any AE related to IMM01-STEM of a Grade 2 unresolved within 48 hours post-injection, or any Grade 3, 4, or 5 related to IMM01-STEM during any time of treatment or during the 48-hour, acute/subacute observation period. | Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of IMMUNA(IMM01-STEM) after 4 weeks of treatment in study participants with muscle atrophy related to KOA | Determined by incidence, type and severity of adverse events graded according to CTCAE v5.0 and CRS revised grading system and defined by clinical relevant findings at day 28 post-treatment, or worsening of previous findings from baseline at day 28 post treatment in: self-reporting, physical examination, vital signs (body temperature, body weight, blood pressure, and heart rate), laboratory data (hematology, clinical chemistry, and urinalysis). | Day 28 | 
| Functionality of the knee joint after 4 weeks of treatment with IMMUNA(IMM01-STEM) in study participants with muscle atrophy related to KOA | Determined by evaluation of participants with changes from baseline at day 28 post treatment in: muscle strength (measured by isometric knee extensor torque), physical function (measured by the 6-minute walk test), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index | Day 28 |