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

A First-in-patient Phase I/II Clinical Study to Investigate the Safety, Tolerability and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Subjects With Severe Complications of Sickle Cell Disease

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
Brief Summary

This study will evaluate two genome-edited, autologous, hematopoietic stem and progenitor cell (HSPC) products - OTQ923 and HIX763 - each reducing the biologic activity of BCL11A, increasing fetal hemoglobin (HbF) and reducing complications of sickle cell disease.

Overall Status Recruiting
Start Date August 25, 2020
Completion Date November 20, 2023
Primary Completion Date November 20, 2023
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with adverse events 24 MONTHS
Number of participants with fetal hemoglobin expression 24 MONTHS
Secondary Outcome
Measure Time Frame
Durability of hematologic engraftment 24 months
Number of participants with treatment induced anti-Cas9 humoral and cellular immunogenicity 24 months
Number of participants with event-free survival 24 months
Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures 24 months
Number of participants with change from baseline of annualized VOC rate by 65% 24 months
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% 24 months
Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures 24 months
Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures 24 months
Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures 24 months
Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures 24 months
Enrollment 20
Condition
Intervention

Intervention Type: Biological

Intervention Name: OTQ923

Description: Single intravenous infusion of OTQ923 cell suspension

Arm Group Label: OTQ923 or HIX763

Other Name: Adult Part A

Intervention Type: Biological

Intervention Name: HIX763

Description: Single intravenous infusion of HIX763 cell suspension.

Arm Group Label: OTQ923 or HIX763

Other Name: Adult Part B

Intervention Type: Biological

Intervention Name: OTQ923 or HIX763

Description: Single intravenous infusion of either OTQ923 or HIX763, based on review of data from Part A and/or Part B by Health agencies after a formal interim analysis

Arm Group Label: OTQ923 or HIX763

Other Name: Children 2-17 years old - Part C

Eligibility

Criteria:

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

Gender: All

Minimum Age: 2 Years

Maximum Age: 40 Years

Healthy Volunteers: No

Overall Contact

Last Name: Novartis Pharmaceuticals

Phone: 1-888-669-6682

Email: [email protected]

Location
Facility: Status: Novartis Investigative Site
Location Countries

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: OTQ923 or HIX763

Type: Experimental

Description: Single intravenous infusion of either OTQ923 or HIX763, Part A - Adults treated with OTQ923; Part B - Adults treated with HIX763 Part C - Children age 2-17 - either OTQ923 or HIX763 based on review of data from Part A and/or Part B by Health agency after a formal interim analysis.

Patient Data Undecided
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Intervention Model Description: A open label, non-randomized, first-in-patient, phase I/II, proof-of-concept study following subjects for two years after transplantation of either genome-edited autologous HSPC investigational drug product. The study consist of 3 parts - Part A include treatment of adults with OTQ923; Part B include treatment of adults with HIX763; Part C include treatment of kids 2-17 years old with either OTQ923 or HIX763

Primary Purpose: Treatment

Masking: None (Open Label)

Masking Description: The is an open-label study.

Source: ClinicalTrials.gov