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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04443907
• Collaborator: (none)
• Enrollment: 30
• Locations: 5
• Arm: 1
• Anticipated Duration (Months): 59.8
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Biological: OTQ923; Biological: HIX763; Biological: OTQ923 or HIX763	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• 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 HIX763A 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
• Masking: None (Open Label)
• Masking Description: The is an open-label study.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 26, 2020
• Anticipated Primary Completion Date: Aug 19, 2025
• Anticipated Study Completion Date: Aug 19, 2025

Arms and Interventions

Arm

Intervention/Treatment

Experimental: OTQ923 or HIX763 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.

Biological: OTQ923; Single intravenous infusion of OTQ923 cell suspension; Other Names: Adult Part A ; Biological: HIX763; Single intravenous infusion of HIX763 cell suspension.; Other Names: Adult Part B ; Biological: OTQ923 or HIX763; 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; Other Names: Children 2-17 years old - Part C

Outcome Measures

Primary Outcome Measures

1. Number of participants with adverse events [24 MONTHS]

   The primary objectives are: safety and tolerability of genome-edited hematopoietic stem cells (HSC) in subjects with sickle cell disease. time to engraftment fetal hemoglobin (HbF) expression

2. Number of participants with fetal hemoglobin expression [24 MONTHS]

   Quantity - fetal hemoglobin (HbF) expression after HSCT

Secondary Outcome Measures

1. Durability of hematologic engraftment [24 months]

   To assess the durability of hematologic engraftment, HbF expression and edited WBC and bone marrow cells

2. Number of participants with treatment induced anti-Cas9 humoral and cellular immunogenicity [24 months]

   To evaluate presence of pre-existing or treatment induced anti-Cas9 humoral and cellular immunogenicity

3. Number of participants with event-free survival [24 months]

   Overall and event free survival

4. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [24 months]

   Determine health status following instruments ASCQ-ME emotional impact

5. Number of participants with change from baseline of annualized VOC rate by 65% [24 months]

   Annualized VOC rate

6. 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]

   Annualized VOC rate

7. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [24 months]

   Determine health status following instruments PROMIS fatique

8. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [24 months]

   Determine health status following instruments PROMIS physical functioning

9. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [24 months]

   Determine health status following instruments ASCQ-ME sleep impact

10. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [24 months]

    Determine health status following instruments ASCQ-ME pain impact

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles Dept.ofChildrensHospital/LA	Los Angeles	California	United States	90027
2	University of Chicago SC - 2	Chicago	Illinois	United States	60637
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-3678
5	Novartis Investigative Site	Milano	MI	Italy	20132

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04443907
• Other Study ID Numbers: CADPT03A12101
• First Posted: Jun 23, 2020
• Last Update Posted: Jun 21, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Gene therapy; genome-edited hematopoietic stem and progenitor cellular therapy; sickle cell; autologous transplant; BCL11A
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of Jun 21, 2022