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

Phase 1TerminatedNCT04443907

Novartis Pharmaceuticals4 enrolled

Overview

This study evaluated 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.

CADPT03A12101 was a multicenter, multi-part, first-in-human, proof-of-concept, open label non-randomized, clinical study in Sickle Cell Disease (SCD) subjects. This study included 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 was divided into the following parts: * Part A - Adult subjects were dosed with OTQ923. * Part B - Assessment of OTQ923 in pediatric patients, however Part B was not opened.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease

Interventions

OTQ923BIOLOGICAL

Single intravenous infusion of OTQ923 cell suspension

OTQ923BIOLOGICAL

Single intravenous infusion of OTQ923, based on review of data from Part A by Health agencies after a formal interim analysis

Eligibility

Sex: ALLMin age: 2 YearsMax age: 40 Years

Medical Language ↔ Plain English

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

Locations (3)

University of Chicago

Chicago, Illinois, United States

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Outcomes

Primary Outcomes

Number of participants with adverse events and serious adverse events

Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

Time frame: up to 24 months

Fetal hemoglobin (HbF) expression 6 months after hematopoietic stem cell transplant (HSCT)

Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

Time frame: at 6 months

Time to reach absolute neutrophil count (ANC) ≥500/μL for 3 consecutive days

Time to engraftment is defined as first of 3 consecutive days when an absolute neutrophil count (ANC) ≥500/μL after receiving OTQ923 was reached.

Time frame: up to 24 months

Secondary Outcomes

Durability of hematologic engraftment

Engraftment durability/persistence by measuring the proportion of alleles with on-target CRISPR modification in peripheral blood (total white blood cells (WBC)) and bone marrow over time up to 24 months

Time frame: up to 24 months

Proportion of subject to achieve 30% of total HbF at 12 months

Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

Time frame: 12 months

Time to achieve 30% total HbF

Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

Time frame: up to 24 months

Time to peak total HbF

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.