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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 : Recruiting
First Posted : June 23, 2020
Last Update Posted : January 10, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 29, 2020
First Posted Date  ICMJE June 23, 2020
Last Update Posted Date January 10, 2023
Actual Study Start Date  ICMJE August 26, 2020
Estimated Primary Completion Date August 19, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2020)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2022)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2020)
  • 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
  • Number of participants with event-free survival [ Time Frame: 24 months ]
    Overall and event free survival
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Sickle Cell Disease (SCD)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Biological: OTQ923
  • Biological: OTQ923
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 2, 2022)		 20
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2020)		 30
Estimated Study Completion Date  ICMJE August 19, 2025
Estimated Primary Completion Date August 19, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04443907
Other Study ID Numbers  ICMJE CADPT03A12101
2019-003489-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP