1. Pathogen Reduction - Evaluation of Mirasol® in a Clinical Trial
Project Update
to the National Advisory Committee
Toronto, April 12, 2012
Rick Trifunov
Director, Plasma Products and Services

2. Goal of the Project
To participate in the evaluation of the Mirasol® Pathogen Reduction Technology System developed by Terumo BCT (formerly known as CaridianBCT) in the context of a clinical trial using Pooled Platelets made from five buffy coats, starting in Q2 2012/13. This multinational clinical trial, sponsored by Sanquin, the national blood operator of the Netherlands and financially supported by Terumo BCT, is already ongoing in Europe and is expected to have completed its recruitment of patients by mid-2014.
Patients from Norway, Neth and Canada, we are late additions.
NAC November 2009

3. Choice of Technology
CBS has opted to first engage in a strategic partnership with Terumo BCT to participate in the evaluation of its Mirasol® Pathogen Reduction Technology
This joint effort does not bind CBS to this specific manufacturer’s technology.
Rationale:
Riboflavin (Vitamin B2) has few safety concerns
Process time is very rapid (approx. 12 minutes/unit)
We have an established working relationship with Terumo BCT
Other guy psoralene, which has to be filtered out after.
We use Terumo aphr machines.
NAC November 2009

4. Benefits expected from this project
Contribute to expand knowledge about safety and efficacy of Mirasol®,
Contribute to increase market availability (licensure) of Pathogen Reduction technologies in Canada,
Gain valuable experience should we later implement this technology or a similar one.

5. Clinical Trial Overview
CBS will join in the PREPAReS clinical trial already underway in the Netherlands under the sponsorship of Sanquin
Phase III study, 618 hemato-oncology patients
Clinical trial primary objective:
To assess the non-inferiority of Mirasol®-treated Pooled Platelets compared to standard of care Pooled Platelets in terms of WHO bleeding complications ≥ grade 2 (expressed as percentage of patients) in hemato- oncological patients with thrombocytopenia.
PREPAReS: Pathogen Reduction Evaluation & Predictive Analytical Rating Score
Pathogen Reduction

6. Clinical Trial Overview
Clinical trial secondary objectives:
To assess the transfusion failures (…)
To assess the % of days with bleedings  WHO grade 2
To evaluate whether clinical factors interact with the different study products leading to a difference in platelet refractoriness.
To assess the safety (adverse reactions).
To assess the transfusion requirement (RBC and PLT).
To assess the transfusion interval.
To assess the incidence of adverse reactions.
To assess the rate of HLA allo-immunization.
To evaluate whether in vitro measures relate to in vivo outcomes measures as the 1-hour and the 24-hour CCI.
Rate of developing anti-bodies, hoping a human result similar to the animals. Bigger than the pathogen reduction (potentially).
Pathogen Reduction

7. Clinical Trial Overview
Study Design: A randomized, single blinded, multicentre non-inferiority trial.
Inclusion criteria:
Age ≥ 18 years.
Expected ≥ 2 platelet transfusion requirements.
Signed informed consent.
Having a hemato-oncological disease
Exclusion criteria:
Micro-angiopathic thrombocytopenia (TTP, HUS) and ITP
Bleeding > grade 2 at randomization (…)
Known immunological refractoriness to platelet transfusions (…)
Treaters will know because the platelets are yellow. Investigator will not know.
Pathogen Reduction

8. Clinical Trial Overview
Exclusion criteria (Continued):
HLA- and/or HPA-allo immunization and/or clinical relevant auto-antibodies.
Indications to use hyper-concentrated (plasma-reduced) platelet concentrates (…)
Pregnancy (or lactating).
Prior treatment with other pathogen-reduced blood products.
Known allergy to riboflavin or its photoactive products.
Pathogen Reduction

9. Clinical Trial Overview
Clinical Trial Overview – in Canada
Randomization
Treated Arm
Mirasol®-treated Pooled Platelets
(5BC pooled platelets)
Approx. 150 patients
Control Arm
Standard of Care Pooled Platelets
(4BC pooled platelets)
Important Notes:
- Use of the “regular” pooled platelets in the control arm (i.e.: Standard of care) and a 5 Buffy Coat product in the treated arm to offset the decrease in platelet viability
- Canada will enroll half of the patients in the PREPAReS study
- Approximately 1,170 Mirasol-treated platelets will be need to be produced (it is estimated that each patient will receive 6 transfusions while on protocol)
- Duration of clinical trial in Canada is estimated to ≈24 months
Need 5 BC because some platelets are lost.
Pathogen Reduction

10. Roles of the clinical trial partners
CBS
Provide products
Provide CT product data
Hospitals
Treat patients
Collect data
McMaster U
Coordinate CT activities
Compile data
Terumo BCT $$
Sanquin
Own CT Protocol
Data analysis
Nancy Heddle from McM, Barb H from CBS,
Pathogen Reduction

11. Summary
Canada will participate in an international clinical trial aiming at evaluating the non-inferiority of Mirasol-treated pooled platelet in terms of bleeding complications as compared to the current standard of care pooled platelet.
Approximately 300 patients will be recruited over 24 months starting in August or September 2012.
Four hospitals will be participating (Tentatively 3 in Ontario and 1 in Nova Scotia). PI meeting to take place in May/June.
Only once the clinical trial is completed (assuming it is successful) will pathogen reduction be considered for national implementation.
Pathogen Reduction

12. Questions?