Study of Safety and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Sickle Cell Disease (SCD)
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| ClinicalTrials.gov Identifier: NCT04443907 |
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Recruitment Status :
Recruiting
First Posted : June 23, 2020
Last Update Posted : May 6, 2023
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sickle Cell Disease | Biological: OTQ923 | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 20 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 2 parts - Part A include treatment of adults with OTQ923; Part B include treatment of kids 2-17 years old with either OTQ923 |
| 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 : | August 26, 2020 |
| Estimated Primary Completion Date : | August 19, 2025 |
| Estimated Study Completion Date : | October 31, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sickle cell disease
| Arm | Intervention/treatment |
|---|---|
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Experimental: OTQ923
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.
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Biological: OTQ923
Single intravenous infusion of OTQ923 cell suspension
Other Name: Adult Part A Biological: OTQ923 Single intravenous infusion of OTQ923, based on review of data from Part A by Health agencies after a formal interim analysis
Other Name: Children 2-17 years old - Part B |
Primary Outcome Measures :
- Number of participants with adverse events [ Time Frame: 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
- Number of participants with fetal hemoglobin expression [ Time Frame: 24 MONTHS ]Quantity - fetal hemoglobin (HbF) expression after HSCT
Secondary Outcome Measures :
- Durability of hematologic engraftment [ Time Frame: 24 months ]To assess the durability of hematologic engraftment, HbF expression and edited WBC and bone marrow cells
- Number of participants with treatment induced anti-Cas9 humoral and cellular immunogenicity [ Time Frame: 24 months ]To evaluate presence of pre-existing or treatment induced anti-Cas9 humoral and cellular immunogenicity
- Overall Survival [ Time Frame: 24 months ]Overall survival is defined as the time from date of start of treatment to date of death to any cause
- Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [ Time Frame: 24 months ]Determine health status following instruments ASCQ-ME emotional impact
- Number of participants with change from baseline of annualized VOC rate by 65% [ Time Frame: 24 months ]Annualized VOC rate
- 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% [ Time Frame: 24 months ]Annualized VOC rate
- Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [ Time Frame: 24 months ]Determine health status following instruments PROMIS fatique
- Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [ Time Frame: 24 months ]Determine health status following instruments PROMIS physical functioning
- Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [ Time Frame: 24 months ]Determine health status following instruments ASCQ-ME sleep impact
- Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures [ Time Frame: 24 months ]Determine health status following instruments ASCQ-ME pain impact
Information from the National Library of Medicine
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| Ages Eligible for Study: | 2 Years to 40 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female subjects age 2-40 years inclusive
- Confirmed diagnosis of sickle cell disease with globin typing (e.g. HbSS, HbSC, HbS/β0-thalassemia or others)
- Performance status >70% (Karnofsky for subjects >16 years of age and Lansky for subjects <16 years of age)
- 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
- Subjects, who have failed, not tolerated or refused hydroxyurea therapy.
Exclusion Criteria:
- Available matched related donor for HSCT
- Clinically significant active infection
- Seropositive for HIV or HTLV
- Active known malignancy, myelodysplasia, abnormal cytogenetics or immunodeficiency
- Prior HSCT or gene therapy
- Known hepatic cirrhosis, bridging hepatic fibrosis or active hepatitis
- Protocol defined iron overload
- Cerebrovascular procedure within one year, including pial synangiosis for Moyamoya
- Severe or progressive arteriopathy or cerebrovascular disease, including Moyamoya
Other protocol defined inclusion/exclusion criteria may apply
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04443907
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Locations
| United States, California | |
| Childrens Hospital Los Angeles Dept.ofChildrensHospital/LA | Withdrawn |
| Los Angeles, California, United States, 90027 | |
| United States, Illinois | |
| University of Chicago SC - 2 | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Kathleen Breen 773-702-0102 kbreen5@bsd.uchicago.edu | |
| Principal Investigator: James Labelle | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Elizabeth Mcnair +1 212 639 3854 McnairE@mskcc.org | |
| Principal Investigator: Jaap Jap Boelens | |
| United States, Tennessee | |
| St Jude Children's Research Hospital | Recruiting |
| Memphis, Tennessee, United States, 38105-3678 | |
| Contact referralinfo@STJUDE.ORG | |
| Principal Investigator: Akshay Sharma | |
| Italy | |
| Novartis Investigative Site | Recruiting |
| Milano, MI, Italy, 20132 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04443907 |
| Other Study ID Numbers: |
CADPT03A12101 2019-003489-41 ( EudraCT Number ) |
| First Posted: | June 23, 2020 Key Record Dates |
| Last Update Posted: | May 6, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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Gene therapy genome-edited hematopoietic stem and progenitor cellular therapy sickle cell autologous transplant BCL11A |
Additional relevant MeSH terms:
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Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia |
Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |