A Study to Assess the Safety and Tolerability of Surgical Implant of MSK-DA01 Cells for Advanced Parkinson's Disease

• Status: Not yet recruiting
• Trial end date: 2023-04-01
• Target enrollment: 10
• Participant gender: All

Summary

The main purpose of this study is to test the safety and tolerability of the study intervention, MSK-DA01, which will be implanted into the brain of study participants during a surgical procedure. This study is the first time that MSK-DA01 is being tested in people.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Treatments: Immunosuppressive Agents

Criteria

Inclusion Criteria:

• Age ≥60 to ≤76 years old

• Idiopathic Parkinson's Disease defined by the modified UK Parkinson's Disease Society Brain Bank criteria

• A minimum time of 5 years from time of PD diagnosis and a maximum time from PD diagnosis of 15 years.

• Prior sufficient treatment comprising levodopa and at least one adjunct therapy, and additional appropriate therapy such as physical therapy.

• Defined levodopa response of ≥ 40% improvement on the basis of MDS-UPDRS part 3

• Baseline Hoehn & Yahr score 0-2 "on" and 3-4 "off"

• Not eligible for deep brain stimulation or have refused deep brain stimulation after evaluation by an independent neurologist or neurosurgeon

• Parkinson's disease medications allowed: any approved oral, transdermal, and/or injectable PD medication and medications must be stable for ≥ 1 month prior to enrollment

• AIMS rating scale score of ≤ 2 for dyskinesia

• "Off" time of ≥ 2 hours daily

• Montreal Cognitive Assessment (MoCA) score ≥ 26

• Hamilton Depression Scale (HAM-D) score ≤17

• Dysthymia allowed with single or two antidepressant medications if at stable dose for > 6 months

• Normal endocrine, renal and liver function as measured by standard laboratory testing unless clinically significant, no blood dyscrasias, no bleeding disorder, and no cardiovascular contraindications for surgery, except for stable and controlled conditions including diabetes type 2 and hypothyroidism.

• All other concomitant disorders must be stable and well controlled, must not constitute a contraindication to general anesthesia or surgery, or interfere with scheduled study assessments

• Women of child-bearing potential must agree to use a highly effective method of contraception from screening until at least 4 weeks after cessation of the oral immunosuppression medication regimen

• Able to participate in all study visits and evaluations, including brain MRI

• Able to give informed consent for study participation and sign Informed Consent Document

• Existence of a study participant partner who may act as potential surrogate over long term for ongoing consent

Exclusion Criteria:

• Clinical features suggestive of a neurodegenerative diagnosis other than Parkinson's disease

• Parkinson's disease with only tremor-based symptoms

• Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease

• Any current or relevant previous history of serious, severe or unstable physical, neurological, or psychiatric illness that may make the subject unlikely to fully complete the study (including significant depression, psychosis, anxiety, cognitive impairment or impulse control disorder)

• Receiving dopamine receptor blocking agents, including typical neuroleptics, prochlorperazine, and metoclopramide at the time of screening or within 3 months prior to screening

• 18F-DOPA PET imaging inconsistent with dopamine deficiency

• Ongoing treatment with intrajejunal or subcutaneous infusion therapies for PD

• History of DBS, lesion therapy, or gene therapy for PD

• Prior surgical or radiation therapy to the brain or spinal cord

• Per assessing clinician discretion, any abnormality on brain MRI that would preclude cell transplantation

• Significant concomitant medical disease limiting life expectancy to less than 24 months from study inclusion, or significant and serious concomitant medical disease that is poorly controlled

• Clinically relevant abnormalities on standard safety laboratory tests, including (blood count, partial thromboplastin time (PTT)), blood chemistry (glucose, blood urea nitrogen (BUN), creatinine, electrolytes), liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGTP), total protein, bilirubin)

• Presence of a condition resulting in high risk of immunosuppressive drugs, including any Virus (HCV), Hepatitis B Virus (HBV), cytomegalovirus (CMV), and Venereal Disease Research Laboratory (VDRL) unless related to immunization or past CMV exposure, risk of tuberculosis.

• Inability to temporarily stop anti-platelet agents or other anti-coagulants without significant risk

• Previous or currently active malignant disease within the past 5 years, except basal cell carcinoma or in situ uterine cervical carcinoma that have been definitively treated

• Use of immunosuppressive drugs including systemic steroids within the previous 3 months

• Severe obesity (>350 lbs) or any condition that prevents use of PET/MRI

• Known substance abuse (recent history of abuse of alcohol or other drugs such as barbiturates, cannabinoids and amphetamines) within last 5 years

• In the opinion of the investigator, presence of any cognitive, behavioral, or psychiatric symptoms that would be deemed contraindications to cell transplantation

• Pregnancy or breastfeeding

• Unable to cooperate or complete self-assessment scales and diaries

• Unable to provide and sign informed consent

• Receipt of another investigational agent or device within the 3 months prior to enrollment

• Contraindication to surgery or general anesthesia

• Contraindication to taking immunosuppressive drugs

• In the opinion of the investigator, any other condition regarded as making subject unsuitable for trial