Study of Safety and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Sickle Cell Disease (SCD)

Novartis

Status and phase: Active, not recruiting; Phase 1

Conditions: Sickle Cell Disease

Treatments: Biological: OTQ923

Study type: Interventional

Funder types: Industry

Identifiers

NCT04443907

CADPT03A12101

2019-003489-41 (EudraCT Number)

Details and patient eligibility

About

This study is evaluating a genome-edited, autologous, hematopoietic stem and progenitor cell (HSPC) product - OTQ923 to reduce the biologic activity of BCL11A, increasing fetal hemoglobin (HbF) and reducing complications of sickle cell disease.

Full description

CADPT03A12101 is a multicenter, multi-part, first-in-human, proof-of-concept, open label non-randomized, clinical study in Sickle Cell Disease (SCD) subjects. This study includes apheresis of mobilized hematopoietic stem and progenitor cells (HSPCs), ex vivo CRISPR/Cas9-mediated genome editing and expansion, followed by myeloablative conditioning and autologous hematopoietic stem cell transplant (HSCT) with follow-up for a minimum of one year and up to two years.

The study is divided into the following parts:

Part A - Adult subjects dosed with OTQ923. Part B - Assessment of OTQ923 in pediatric patients. Part B will not be opened.

Enrollment: 5 patients

Sex: All

Ages: 2 to 40 years old

Volunteers: No Healthy Volunteers

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/β0-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.

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

5 participants in 1 patient group

OTQ923

Experimental group

Description:

Single intravenous infusion of OTQ923 Part A - Adults treated with OTQ923; Part B - Children age 2-17 treated with OTQ923 based on review of data from Part A by Health agency after a formal interim analysis.

Treatment:

Biological: OTQ923

Biological: OTQ923