Primary: To assess the safetyand tolerabilityofischemia-tolerantallogeneic humanmesenchymal stemcells (hMSCs) manufactured byStemedicaversusplaceboadministered intravenouslyto subjectswith mild to moderate dementia dueto Alzheimer’s disease.
To assess thepreliminaryefficacyofhMSCs versus placebo in subjects with Alzheimer’s-relateddementia, as evidenced byneurologic, functional,and psychiatricendpoints.
Stemedica International has conductedextensive preclinical experiments usingStemedica-manufactured hMSCs in a mousemodel ofAlzheimer’s disease(APPPS1) that developsearlyand robust cerebral amyloid pathology.TheAPPPS1 transgenic model develops initial Abetaamyloid plaques in thecortexby6 weeks of age. Preclinical experiments conducted byStemedica International using intravenous(IV) deliveryof hMSCs demonstrated efficient Abetaamyloid plaque removalin thebrain parenchymaof theAPPPS1 mouse model.The beneficialeffect on Abeta plaqueswas accompanied byanoverall decrease in neuroinflammation markers(e.g., reduction ofmicroglia activation) withoutthe appearance ofamyloidclearance side effectssuch as cerebral amyloid angiopathyof microhemorrhages.
Thepositive impact ofIVtreatment with hMSCS on Alzheimer pathologyachieved in transgenicmice constitute the preclinical basis forthe translation ofthisstem cell therapyconcepttowardsclinical application in Alzheimer patients.
Seventeen (17) subjectswith ischemic strokehave been treated in aPhaseI/IIa studywithhMSCs manufactured byStemedica. Theobjectives of this studywereto assess the safetyandtolerabilityof Stemedica-manufactured hMSCs administered intravenously,and to assess thestudytreatment’s effectson neurologic, functionaland motor deficits. Demographic informationis available for 15subjects. Thirteen (13) malesand 2 females, ranging from 38 to 84years ofage, weretreated in this study.ThePhase1 dose-escalation portion ofthistrial has beencompleted. Three cohorts of patients, 5 patients in eachcohort, weretreated at doses of0.5, 1.0,and 1.5 million cells per kgof patient’s bodyweight. A Data and SafetyMonitoringBoard wasemployed in this studyand voted unanimouslytoproceed to thePhase2 portionofthe studyatthe doseof 1.5million cells per kgof patient’s bodyweight. Two subjectshave been treated inthe Phase2 portion ofthis trial. Safetyassessments wereperformedon days 1, 2, 3, 4, 10 and onmonths 1, 3, 6, 9 and 12.
No patients discontinued the studydueto anadverse event (AE). Therewere33 AEs reported in17 subjects treated:15 wereclassified as mild and18 were classified as moderatebytheinvestigator(s); nonewere severe. Ofthese33 AEs, 24 were classified as unrelated to studydrugand 8 were classifiedasunlikelyto be related to studydrugbythe investigator(s). OnlyoneAEwas classifiedas possiblyrelated to studydrug:“foul smell urine”. This AE was rated “mild” bythe investigator. Itcommencedsoon after studydrugtreatment with 1 millioncells/kgandresolved within one day.
Seven (7)serious adverse events werereported inthis studyand all were classified as unrelatedto studydrugbythe investigator(s). CT scans with and without contrast ofthe chest, abdomenand pelvis were reviewed; therewereno clinicallysignificantabnormalities on post-treatmentscans. Also, there wereno significantabnormalities on post-treatment physical exams or vitalsigns.In summary, participants with ischemic strokehavebeen treated withhMSCsmanufactured byStemedicaat doses up to 1.5 million cells / kgwith excellent tolerabilityand noapparent safetyconcerns.
This is a PhaseIIa multi-center,randomized, single-blind, placebo-controlled, crossover studyinsubjects with mild to moderate dementia dueto Alzheimer’s disease.Onlythe subject and theircaregiver will be blindedto the studytreatment. Thestudywill consist of two cohorts ofsubjects (20 subjects percohort), randomized in a1:1 allocation to receiveactive studydrugorplacebo. Cohort 1 will receive a single intravenous dose ofhMSCs of1.5 millioncells perkilogram bodyweight ontheir StudyDay1,and Cohort 2 will receiveequalvolumeofLactatedRinger’s Solutionon theirStudyDay1. At the six-month timepoint foreach subjectafter theirfirst infusion, Cohort 1 will receive asingle intravenous dose of Lactated Ringer’s Solution andCohort 2 will receive asingle intravenous dose of hMSCs at 1.5 million cells per kilogram of thesubject’s bodyweight. No subject will receivemorethanthemaximumdosage of 150 millioncells in this study. Approximately40 subjects will be enrolled in this study. Subjects whodiscontinuethe studybeforeMonth 6 will be replaceduntil at least 20 subjects in each cohorthave been enrolled.
Subjects will be administered the intravenous doseof hMSCsor placebo with frequentmonitoringuntil discharged from theclinic.Subjectswill be evaluated perthe followingpost-treatment schedule: StudyDay4, Day10, Month1, Month 3, Month 6, four (4) daysafter Month
6, ten (10) daysafter Month 6,Month 7, Month 9,Month 12, Month 15, and Month 18. If thesubject terminates thestudybeforeMonth 18, theywill befullyevaluated atan EarlyTermination visit. Duringinfusion andfollow-upof subjects,the safetyprofileof hMSCs willbe determinedas well asefficacyassessments throughout the18-month follow-up period.Anindependent Data and SafetyMonitoring Board(DSMB) will conduct periodicsafetyreviewsaccordingto thefollowingschedule: after 5 subjects in each treatment group have completedDay10 studyvisit; after10 subjects in each treatment group have completed Month 3 studyvisit;if astudydrug-related serious adverse event occurs in a subject enrolled inthis study; if astudydrug-related unexpectedadverse event occurs in asubject enrolled in this study; and at theend of
the study. An interim analysis of safetyand efficacydatawill be performedafterat least 10subjects in each treatment group have completedMonth 6 visit assessments. Figure 1 Clinical Trial Flowchart