Investigation of the Safety and Efficacy of NTCELL® [Immunoprotected (Alginate-Encapsulated) Porcine Choroid Plexus Cells for Xenotransplantation] in Patients With Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      To assess the safety of xenotransplantation of NTCELL [immunoprotected
      (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease, assessed
      over the duration of the study, by monitoring the occurrence of adverse events and serious
      adverse events, including clinical and laboratory evidence of xenogeneic infection in
      transplant recipients and their partners/close contacts. Subsequent safety follow-up will
      include lifelong monitoring for clinical and laboratory evidence of xenogeneic infection.

      To assess the efficacy of xenotransplantation of NTCELL [immunoprotected
      (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease. This will
      be quantified by testing the secondary endpoints of the trial as described below (see
      Endpoints/Outcome Measures).
    

Detailed description: 
      Parkinson's disease is characterized by widespread neural degeneration, particularly in the
      substantia nigra and its projections to the basal ganglia. Current therapy for Parkinson's
      disease is purely symptomatic. There is a pressing need for a treatment that reverses or
      slows the degeneration of the nigrostriatal pathway.

      Numerous transplant-based therapies have attempted to support, repair or replace the
      degenerating nigrostriatal neurons. These have included the transplantation of foetal and
      other neuronal stem cells, gene transfers, and the implantation of devices releasing neural
      growth factors. All these have been shown to have some effectiveness in animal models, but
      have been generally disappointing in human studies.

      Intracranial choroid plexus cell transplantation has the potential to deliver biological
      neural agents for the treatment of Parkinson's disease which cannot be achieved by
      conventional treatment. The overall aim of delivering neural proteins and compounds over many
      months to the basal ganglia of the brain is to enhance neural repair currently not possible
      with antiparkinsonian medication or deep brain stimulation (DBS).

      As animal-derived tissues have to be protected from immune rejection when transplanted into
      humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine
      choroid plexus cells are preferably implanted without the use of immunosuppressive drugs
      which cause significant morbidity. To protect them from immune rejection, the cells can be
      encapsulated in alginate microcapsules which permit the inward passage of nutrients and the
      outward passage of biologic neural proteins and compounds normally secreted by choroid plexus
      cells. Alginate-encapsulated porcine choroid plexus cells implanted into the brain without
      immunosuppressive drugs have survived rejection for many months in animal studies.

      NTCELL comprises neonatal porcine choroid plexus cells encapsulated in alginate
      microcapsules.

      The bilateral dose that will be administered to the 18 patients (initially 3 groups of 6
      patients, randomised 4:2 NTCELL:sham surgery) enrolled in this trial will be up to a total of
      twice the human equivalent dose administered unilaterally in LCT's non-human primate study.
      Thus up to 240 NTCELL microcapsules (± 5%) administered on each side of the brain.

      If there are no significant safety issues after implantation of the first group of patients,
      the second group of patients will then be scheduled to receive implants of NTCELL.

      If there are no significant safety issues after implantation of the second group of patients,
      the third group of patients will then be scheduled to receive implants of NTCELL.

      This study will adopt an adaptive design in respect to the choice of dose of NTCELL for the
      fourth group of patients (those patients who originally received sham surgery in Groups 1-3).
      Following unblinding of the study after Groups 1-3 have reached 26-week follow-up, an interim
      analysis, for safety and efficacy, will be undertaken.

      If there are no significant safety issues, the last group of patients, Group 4, (who
      originally received sham surgery) will be scheduled to receive NTCELL implants. The dose of
      NTCELL given will be determined by the DSMB following a proposal from the Principal
      Investigator, based on the results of the interim analysis.

      Parkinson's disease patients will be followed up for 26 weeks after receiving either an
      implantation of NTCELL or sham surgery.
    

Intervention name(s): NTCELL Implantation; Sham Surgery
Intervention type(s): Biological; Other
Intervention description(s): NTCELL Implantation; Sham Surgery
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parkinson's Disease; Xenotransplantation; choroid plexus