Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID

Stirnadel-Farrant, Heide; Kudari, Mahesh; Garman, Nadia; Imrie, Jessica; Chopra, Bikramjit; Giannelli, Stefania; Gabaldo, Michela; Corti, Ambra; Zancan, Stefano; Aiuti, Alessandro; Cicalese, Maria Pia; Batta, Rohit; Appleby, Jonathan; Davinelli, Mario; Ng, Pauline

doi:10.1186/s13023-018-0791-9

Orphanet Journal of Rare Diseases

Table 1 Efficacy and safety endpoints of the Strimvelis registry post-authorisation safety study

From: Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID

	Baseline data collected from OSR medical records^a		Collected through standard of care procedures performed by the patient’s local HCP (e.g. referring paediatric immunologist) For patients treated in the clinical studies, baseline and follow-up data will be obtained retrospectively from records at OSR or trial database
Observational data and minimal time points for their collection	Pre-treatment phase^f	Treatment phase (Year 0)^f	Annually Years 1 to 11	Year 13	Year 15	>Year 15
General
Medical history	✓
Demographics	✓
Gene therapy date / dose / lot no.		✓
Growth (height and weight)	✓		✓	✓	✓
Survival			✓	✓	✓	✓^g
Fertility and pregnancy outcomes			✓	✓	✓	✓^g
Oncogenesis			✓	✓	✓	✓^g
Development and QoL	✓		✓	✓	✓
Use of medication/treatments of interest
ERT, HSCT, radiotherapy, cytotoxic agents			✓	✓	✓
AEs
Reported SAEs	✓	✓	✓	✓	✓
Reported AEs	✓	✓	✓	✓	✓
AEs of interest^a	✓	✓	✓	✓	✓
Specialist lab assessments^b
dAxP RBCs	✓	✓	✓	✓	✓
Busulfan AUC		✓
Immunogenicity^c		✓	✓	✓	✓
Vector copy number^d		✓	✓	✓	✓
T-cell function	✓	✓	✓	✓	✓
RIS and RCR^e			✓	✓	✓
General lab assessments^b
Peripheral lymphocyte counts	✓	✓	✓	✓	✓
Laboratory blood test results	✓	✓	✓	✓	✓

AE adverse event, ADA adenosine deaminase, AUC area under the curve, dAxP deoxyadenosine nucleotide, ERT enzyme replacement therapy, HCP healthcare practitioner, HSCT haematopoietic stem cell therapy, OSR Ospedale San Raffaele, PEG polyethylene glycol, RBC red blood cell, RCR replication competent retrovirus, RIS retroviral insertion site, SAE serious AE
^aAEs and SAEs related to medical or surgical procedures associated with Strimvelis administration (e.g., central venous catheter) or related to busulfan conditioning; hypersensitivity (e.g., angioedema, anaphylactic reactions, systemic allergic events and severe cutaneous adverse reactions); autoimmunity, and oncogenesis
^bWhen the test is performed as part of standard of care by the treatment centre, local specialist HCP or primary care physician
^cAt baseline, data related to titres of anti-PEG-ADA antibodies, their cross reactivity to human ADA and neutralising activity will be collected. After baseline, data related to titres of anti-ADA antibodies and their neutralising activity will be collected if available
^dData collected from assessment during treatment process and when it has been performed by a HCP during follow-up as part of standard of care
^eData from RIS analysis and replication competent retrovirus will only be collected if a HCP has performed these tests (e.g. following suspected malignancy or after a diagnosis of malignancy)
^fPre-treatment phase: defined as the period from when eligibility for Strimvelis is confirmed in OSR, including when central venous catheter insertion and back-up bone marrow harvest occur, up to the beginning of the Treatment phase. Treatment phase: defined as the period from when the bone marrow harvest for treatment occurs, including conditioning with busulfan and the infusion of transduced CD34+ cells up to and including tests conducted as part of that process
^gData on areas of long-term interest (i.e. death, oncogenesis, fertility and pregnancy outcomes) collected every 2 years while the registry is open

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ISSN: 1750-1172

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