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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04443907
Recruitment Status : Not yet recruiting
First Posted : June 23, 2020
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
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

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
Estimated Study Start Date : September 29, 2020
Estimated Primary Completion Date : November 20, 2023
Estimated Study Completion Date : November 20, 2023

Resource links provided by the National Library of Medicine


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 Name: Adult Part A

Biological: HIX763
Single intravenous infusion of HIX763 cell suspension.
Other Name: 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 Name: Children 2-17 years old - Part C




Primary Outcome Measures :
  1. 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

  2. Number of participants with fetal hemoglobin expression [ Time Frame: 24 MONTHS ]
    Quantity - fetal hemoglobin (HbF) expression after HSCT


Secondary Outcome Measures :
  1. Durability of hematologic engraftment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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% [ Time Frame: 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% [ Time Frame: 24 months ]
    Annualized VOC rate

  7. 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

  8. 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

  9. 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

  10. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  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


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
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04443907    
Other Study ID Numbers: CADPT03A12101
First Posted: June 23, 2020    Key Record Dates
Last Update Posted: June 23, 2020
Last Verified: June 2020
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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