Study of safety and efficacy of genome-edited hematopoietic stem and progenitor cells in sickle cell disease (SCD)
- Conditions
- Sickle Cell Disease (SCD)MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003489-41-IT
- Lead Sponsor
- OVARTIS PHARMA AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
Inclusion Criteria:
1. Male or female subjects age 2-40 years inclusive
2. Confirmed diagnosis of sickle cell disease with globin typing (e.g. HbSS, HbSC, HbS/ß0-thalassemia or others)
3. Performance status >70% (Karnofsky for subjects >16 years of age and Lansky for subjects <16 years of age)
4. At least one of the following indicators of disease severity as defined in the protocol - Vaso-occlusive pain crisis, Acute chest syndrome, Recurrent priapism, prior stroke, receive chronic transfusions, Red cell
alloimmunization
5. Subjects, who have failed, not tolerated or refused hydroxyurea therapy.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion Criteria:
1. Available matched related donor for HSCT
2. Clinically significant active infection
3. Seropositive for HIV or HTLV
4. Active known malignancy, myelodysplasia, abnormal cytogenetics or
immunodeficiency
5. Prior HSCT or gene therapy
6. Known hepatic cirrhosis, bridging hepatic fibrosis or active hepatitis
7. Protocol defined iron overload
8. Cerebrovascular procedure within one year, including pial synangiosis for Moyamoya
9. Severe or progressive arteriopathy or cerebrovascular disease, including Moyamoya
Other protocol defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objectives are:<br>- safety and tolerability of genome-edited hematopoietic stem cells (HSC) in subjects with sickle cell disease.<br>- time to engraftment<br>- fetal hemoglobin (HbF) expression Quantity - fetal hemoglobin (HbF) expression after HSCT;Secondary Objective: To assess the durability of hematologic engraftment, HbF expression and edited WBC and bone marrow cells.<br>To evaluate presence of preexisting or treatment induced anti-Cas9 humoral and cellular immunogenicity.<br>Overall and event free Survival.<br>Determine health status following instruments ASCQME, and PROMIS fatique and PROMIS physical functioning.<br>Annualized VOC rate.;Primary end point(s): Number of participants with adverse events.<br>Number of participants with fetal hemoglobin expression.;Timepoint(s) of evaluation of this end point: 24 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Durability of hematologic engraftment.<br>Number of participants with treatment induced anti-Cas9 humoral and cellular immunogenicity.<br>Number of participants with event-free survival.<br>Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures.<br>Number of participants with change from baseline of annualized VOC rate by 65%.<br>Number of participants with change from baseline of annualized SCD complications (aggregate of VOC, ACS, priapism and stroke) and if relevant, rate of transfusion by 65%;Timepoint(s) of evaluation of this end point: 24 months