Muscle Performance, Sarcopenic Obesity
Conditions
Keywords
Muscle Performance, Sarcopenic Obesity
Brief summary
Placebo controlled study for safety and efficacy of IMM01-STEM on muscle performance in seniors with obesity and muscle weakness
Detailed description
This will be a two-phase, placebo-controlled, dose expansion study that begins with 4 parallel dosing groups and one placebo control group (phase IIa). The treatment period and follow up will last 16 weeks, then an interim adaptation will initiate the second phase of the study (IIb). The study will target safety parameters, body composition, and muscle strength and function. Additional metabolic, inflammatory, and muscle-adipose crosstalk markers will be monitored. During screening, a wearable activity tracker will be assigned to each participant to establish a baseline of daily physical activity. The treatment will be administered by intramuscular (IM) in a regimen of two injections per week with 2-3 days intervals between injections, for 4 weeks. The dosing groups vary by IMM01-STEM total protein and will be adjusted for identical volumes or equivalent saline volume for placebo. The proposed doses will be 0.5 mg administered twice per week; 1 mg once per week (alternating with a placebo given on the second visit of the week); 1 mg twice per week; and 2 mg once per week (also alternating with placebo). Each participant will be evaluated at baseline, at the time of treatment administration during the treatment period, then monthly until the end of trial. Interim analysis with the purpose of design adaptation will be performed after 10 participants from each group have completed treatment. This point will be marked by the date when the final participant to enroll has completed the final treatment on Week 12. This would occur about 16 weeks after the final participant starts treatment. Statistical analysis will be performed on all recorded outcomes. All participants will continue to be followed-up per protocol for additional 8 weeks. Post-adaptation, enrollment will be restarted in accordance with the new randomization rules in a 2-arm placebo-controlled study (IIb). The best responding dose will be chosen, or the most convenient treatment (lowest dose, less frequent administration) in the case that all treatment arms responded equally at interim analysis. An amended clinical protocol will be submitted prior initiation of the phase IIb study. Study participants will sign a written Informed Consent Form (ICF) prior to any study-related procedures. Treatment must begin within 28 days of signing the ICF, during which participant screening and any necessary drug wash-out period must be completed. Screening assessments will be conducted as specified in the Schedule of Activities of the protocol, after which the study participants' eligibility will be determined based on the inclusion and exclusion criteria. Site staff will administer study medication by IM injection in the gluteal area using a small-gauge needle at all scheduled treatment visits. If gluteal area is not feasible, alternatively i.m. injection can be administered in the quadriceps or deltoid area. After each administration of study medication, participants will be observed for 1 hour to monitor for acute injection-related reactions and other early onset treatment-related AEs.
Interventions
BIOLOGICALIMM01-STEM
IMM01-STEM is an allogeneic cell-free secretome product derived from partially differentiated human stem cells derived from a pluripotent embryonic stem cell line that was established from a single donor IVF discarded blastocyst. The cells are cultivated in bioreactors and the product of their secretion is collected, purified and concentrated to a standardized formulation. The secretome contains a mixture of molecules related to immunomodulation, growth, and extracellular matrix remodeling. This intervention is given 2mL twice a week.
OTHERPlacebo
Saline. This intervention is given 2mL twice a week.
BIOLOGICALIMM01-STEM alternating with placebo (saline)
This intervention consists of IMM01-STEM given once a week and placebo given one a week. IMM01-STEM is an allogeneic cell-free secretome product derived from partially differentiated human stem cells derived from a pluripotent embryonic stem cell line that was established from a single donor IVF discarded blastocyst. The cells are cultivated in bioreactors and the product of their secretion is collected, purified and concentrated to a standardized formulation. The secretome contains a mixture of molecules related to immunomodulation, growth, and extracellular matrix remodeling.
Sponsors
Immunis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The following roles indicated below will not be made aware of the treatment group assignment during the trial: Participants Investigators Outcomes assessor The person responsible for drug dispensing (pharmacist) will be unblinded Sponsor staff or designees may be unblinded to complete ongoing safety oversight and surveillance reporting. A planned unblinding will take place at the interim analysis for dose selection in the next phase and futility.
Intervention model description
STEM-META is a placebo-controlled, randomized, dose expansion study that begins with 4 parallel dosing groups and one placebo control group (phase IIa). The treatment period and follow up will last 16 weeks, then an interim adaptation will initiate the second phase of the study (IIb). Treatment Groups Group 1 - Placebo - 2 mL USP injectable saline, twice a week Group 2 - 0.5 mg total protein in 2 mL final volume, twice a week Group 3 - 1 mg total protein in 2 mL final volume, once a week, alternating with saline Group 4 - 1 mg total protein in 2 mL final volume twice a week Group 5 - 2 mg total protein in 2 mL final volume, once a week, alternating with saline
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Sex: male or female * Age 60 to 80 years of age at the time of signing the informed consent. * Race/nationality: all races and ethnicities accepted for which there are validated reference values for obesity and sarcopenia diagnostic criteria * Disease characteristics: To be eligible, the participant must meet at least one criterion for obesity and at least one criterion for sarcopenia, as defined below: Obesity: Abdominal obesity defined by a waist circumference ≥ 40 inches (102 cm) for men, ≥ 35 inches (88 cm) for women (American Heart Association) Abdominal obesity as a waist-to-hip ratio of at least 0.90 in men and 0.85 or more for women (World Health Organization) Sarcopenia: Grip strength women: \< 16 kg, men: \< 27 kg in the dominant hand Gait speed \< 0.8 m/s (men and women) Acceptable stages: STAGE I: No complications attributable to altered body composition and skeletal muscle functional parameters STAGE II: Presence of up to two complications attributable to altered body composition and skeletal muscle functional parameters (e.g. metabolic syndrome components, disabilities resulting from high fat mass and/or low muscle mass, cardiovascular and respiratory disease). Limitations apply (see
Exclusion criteria
). * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the STEM-META clinical protocol * In order to understand the nature of this study it is expected that most participants will be able to speak, read, and understand English, or Spanish however, additional translations of the informed consent may be made available after study initiation to include additional languages for participants * Study participant is willing and able to comply with all study requirements, according to the judgment of the Investigator. * To be eligible for enrollment and for each treatment administration, the vital signs pre-dose, should be in the following ranges. If the vitals are outside of the range, will be reassessed 3 times at 10 minutes resting intervals. Heart rate \>50 and \<100 bpm Systolic pressure \>100 and \<170 mmHg Diastolic pressure \>50 and \<100 mmHg Blood oxygenation (by pulse-oximetry) \>95%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Time Frame: Day 0 to Day 28 | Safety and tolerability of the IP will be measured by regular monitoring of study subjects' vital signs, blood and urine testing, symptom assessments, physical examinations and physical function testing to identify changes that may be related to the IP. Monitoring begins before treatment and continues for three months following the completion of treatment. |
| Change over time in gait speed | Time Frame: Day 0 to Day 171 | Muscle strength and function efficacy information from this measure will be used to determine a dosing regimen for a confirmatory expanded study. This will be done using the The European Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria of sarcopenia gait speed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change over time in grip strength | Time Frame: Day 0 to Day 171 | Muscle strength and function efficacy information from this measure will be considered for alternative efficacy outcome post interim adaptation. This will be done using the The European Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria of sarcopenia hand grip strength. |
| Change over time in body composition using DXA | Time Frame: Day 0 to Day 171 | This outcome may be considered for alternative efficacy outcome post interim adaptation. |
| Change over time in actigraphy parameters as reported by a wearable activity tracker | Time Frame: Day 0 to Day 171 | This purpose of this measurement is to evaluate additional outcomes that may be considered for alternative efficacy outcome post interim adaptation. |
Countries
United States
Contacts
STUDY_DIRECTORTom Lane, PhD
Chief Science Officer at Immunis, Inc.
Outcome results
None listed