Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    1801 | sickle cell disease
Previous Study | Return to List | Next Study

Gene Transfer for Patients With Sickle Cell Disease

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: NCT02186418
Recruitment Status : Recruiting
First Posted : July 10, 2014
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
Aruvant Sciences GmbH

Brief Summary:
The purpose of this Phase 1/2 study is to determine the feasibility and safety of stem cell collection and gamma-globin gene transfer, and success of gene correction in subjects with sickle cell disease

Condition or disease Intervention/treatment Phase
Anemia, Sickle Cell Genetic: ARU-1801 Phase 1 Phase 2

Detailed Description:
This study will assess the feasibility, safety and efficacy of gene transfer using ARU-1801 (CD34+ cells transduced with the gamma-globin lentiviral vector). Gene transfer will occur ex-vivo into CD34+ enriched human bone marrow or plerixafor-mobilized peripheral blood hematopoietic stem cells (HSC) collected from subjects with severe sickle cell disease (SCD). Subjects will undergo reduced intensity chemotherapy conditioning with single-dose melphalan to facilitate engraftment of ex-vivo ARU-1801 via IV infusion. Subjects will return to the study site at regular intervals for follow-up for 2 years after the ARU-1801 infusion. It is anticipated that a separate long-term follow-up (LTFU) clinical study will be initiated, in which all subjects completing the 2 year study visit will be asked to consent and enroll, and will followed for a further 13 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Gamma Globin Lentivirus Vector
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gene Transfer for Patients With Sickle Cell Disease Using a Gamma Globin Lentivirus Vector: An Open Label Phase 1/2 Pilot Study
Study Start Date : July 2014
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2035

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ARU-1801
Autologous CD34+ hematopoietic stem cells transduced ex-vivo with gamma-globin lentiviral vector. Administered via IV infusion.
Genetic: ARU-1801

Autologous CD34+ hematopoietic stem cells transduced ex-vivo with a gamma-globin lentiviral vector

  • Subjects with sickle cell anemia will undergo hematopoietic stem cell procurement by bone marrow harvest or apheresis after mobilization with plerixafor
  • Reduced intensity chemotherapy conditioning with single dose melphalan will be used to facilitate engraftment of ex-vivo transduced cells.




Primary Outcome Measures :
  1. Incidence of Grade 3 allergic reaction [ Time Frame: From infusion (Day 0) to 15 years ]
    Incidence of Grade 3 allergic reaction associated with infusion of transduced cell product

  2. Incidence of Grade 4 infection [ Time Frame: From infusion (Day 0) to 15 years ]
    Incidence of Grade 4 infection following infusion of transduced cell product uncontrolled for ≥14 days

  3. Incidence of Grade 4 neutropenia [ Time Frame: From date of chemotherapy clearance visit to 15 years post-infusion of transduced cells ]
    Incidence of Grade 4 neutropenia lasting >1 month following melphalan

  4. Incidence of Grade 3 or 4 organ toxicity [ Time Frame: From screening to 15 years post-infusion of transduced cells ]
    Incidence of Grade 3 or 4 organ toxicity attributable to study procedures

  5. Incidence of Adverse Events (AEs) [ Time Frame: From screening to 15 years post-infusion of transduced cells ]
  6. Incidence of Serious Adverse Events (SAEs) [ Time Frame: From screening to 15 years post-infusion of transduced cells ]
  7. Incidence of death due to study procedures [ Time Frame: From screening to 15 years post-infusion of transduced cells ]
  8. Incidence of hematological malignancy [ Time Frame: From infusion (Day 0) to 15 years ]
    Incidence of hematological malignancy due to vector insertion

  9. Incidence of hematological cancer [ Time Frame: From screening to 15 years post-infusion of transduced cells ]
    Incidence of hematological cancer related to investigational product or study medications/procedures

  10. Time to neutrophil recovery [ Time Frame: From ≥36 hours before Day 0 to 2 years post-infusion of transduced cells ]
    Number of days from melphalan-induced nadir to the first of 3 consecutive absolute neutrophil counts ≥500 cells/µL

  11. Time to platelet recovery [ Time Frame: From ≥36 hours before Day 0 to 2 years post-infusion of transduced cells ]
    Number of days from melphalan-induced nadir to the first of 3 consecutive platelet counts >50,000 cells/µL and independent of platelet transfusion for ≥7 days consecutive days.

  12. ≥8x10^6kg viable CD34+ cells [ Time Frame: Up to Year 2 ]
    Number of subjects with a total number of CD34+ cells recovered from all collections combined (mobilized peripheral blood and bone marrow) of at least ≥8x10^6kg viable CD34+ cells

  13. ≥4x10^6 CD34+ cells/kg body weight transduced [ Time Frame: Up to Year 2 ]
    Proportion of subjects for which a minimum of 4x10^5 CD34+ cells/kg body weight from all collections combined have been successfully transduced

  14. Bone marrow aspirates with ≥1% gene-marked cells [ Time Frame: Infusion (Day 0) to 1 year ]
    Number of subjects with bone marrow aspirates at 1-year post-infusion with ≥1% gene-marked cells


Secondary Outcome Measures :
  1. Quantity of Hb (hemoglobin) subtypes [ Time Frame: Months 6, 12, 18, 24 and year 3, 4, 5 ]
    Quantification of HbF^G16D and other Hb subtypes, including HbF (endogenous), HbS, adult Hb (HbA), HbA2 and, if applicable, HbC and HbE

  2. Change in proportion of antisickling/sickling hemoglobin [ Time Frame: Baseline to Month 6 through 12 ]
    Change in the proportion of antisickling/sickling hemoglobin ([HbF+HbF^G16D+HbA2]/HbS) in months 6-12 post-transplantation compared to baseline

  3. Percentage of F-RBC (fetal hemoglobin content in red blood cells) [ Time Frame: Months 6, 12, 18, 24, 36 ]
    Measured by flow cytometry

  4. Percentage of F-retics (fetal hemoglobin content in reticulocytes) [ Time Frame: Months 6, 12, 18, 24, 36 ]
    Measured by flow cytometry

  5. Presence of vector copies in white blood cell fraction [ Time Frame: Days 30, 60, 90, Months 4, 5, 6, 9, 12, 18, 21, 24 ]
  6. Presence of vector copies in bone marrow [ Time Frame: Prior to ARU-1801 infusion, month 6, 12, 18, 24 and 36 ]
    Measured by qPCR and DNA

  7. Presence of gene-marked colony-forming unit cells (CFU-c) in bone marrow (BM) indicting gene transfer [ Time Frame: Prior to ARU-1801 infusion, month 6, 12, 18, 24 and 36 ]
    Measured by CFU-c assay by qPCR on individual CFU-c

  8. Number of annualized vaso-occlusive episodes (VOEs) pre-transplant versus post-transplant [ Time Frame: Baseline to year 15 ]
    Change in disease severity

  9. Frequency of opioid use pre-transplant versus post-transplant [ Time Frame: Baseline to year 15 ]
    Change in disease severity

  10. Change in QoL (Quality of Life) [ Time Frame: Baseline, month 4, 5, 6, 12 and 24 and year 3, 4, 5 ]
    Measured by adult sickle cell quality of life measurement (ASCQ-Me®)



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Signed informed consent form.
  • Has confirmed diagnosis of sickle cell disease (SCD)
  • Has severe sickle cell disease, defined as one or more of the following:

    1. Minimum of two episodes of clinically diagnosed acute chest syndrome (ACS) requiring hospital admission, or one life threatening episode of ACS requiring intensive care unit (ICU) admission for exchange transfusion and/or intubation, or frequent ACS episodes which necessitate treatment with chronic transfusion therapy.
    2. Frequent painful vaso-occlusive episodes (VOEs) which significantly interfere with normal life activities, defined as a history of 2 or more severe acute sickle pain events per year requiring additional treatment at a medical facility outside of home pain management over the preceding 2-year period prior to study enrollment, or that necessitate chronic transfusion therapy.
    3. Subjects on chronic transfusion therapy for severe disease symptoms other than those listed above, and which interfere with normal life activities.
  • Has failed hydroxyurea therapy, was unable to tolerate hydroxyurea therapy, or has actively made the choice to not take the recommended daily hydroxyurea advised for severe disease (Note: must be off hydroxyurea therapy for 2 months prior to stem cell collection). If refusing hydroxyurea, the subject must document that they have been educated about the benefits and continue to refuse the treatment. Patients placed on chronic transfusion therapy instead of hydroxyurea for severe disease are eligible. Subjects unable to take hydroxyurea due to financial or safety monitoring constraints are eligible.
  • Has adequate functional status and organ function as determined at Screening.

Exclusion Criteria

  • Female subjects who are pregnant or lactating/breastfeeding.
  • Female subjects who are not surgically sterile, postmenopausal or who refuse to practice effective method of birth control as determined by the Investigator for one year after receiving the study drug. Women must also agree not to breastfeed for 1 year after receiving the study drug.
  • Any participant of reproductive potential who refuses to agree to use an appropriate contraceptive method determined by the Investigator, for 1 year after receiving the study drug.
  • Patients with an active malignant disease or receiving treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin).
  • Current diagnosis or history of hepatitis B, hepatitis C, or HIV.
  • Has received another study drug within 30 days, or 5 half-lives of the last dose (whichever is longer), prior to screening.
  • Has severe obstruction, restriction or diffusion defect on pulmonary function tests.
  • Has uncontrolled bacterial, viral or fungal infections within 1 month prior to starting the conditioning part of the study. Subjects with fever should wait for symptoms to resolve before starting the conditioning part of the study.
  • Has a history of stroke or is at moderate to high risk of primary stroke (eg receiving chronic transfusions or hydroxyurea for primary prevention of stroke; has severe cerebral vasculopathy defined as moderate stenosis in >2 arterial segments; and/or has sever stenosis/occlusion in ≤2 segments in the polygon of Willis or presence of Moyamoya-like disease).
  • Patients with alpha thalassemia sickle cell disease.
  • Has previous liver biopsy showing cirrhosis, bridging hepatic fibrosis, or active hepatitis; or has received chronic transfusions and has previous evidence of iron overload and evidence of liver fibrosis by noninvasive liver imaging.
  • Has a matched sibling donor, unless the subject has declined this option or this option is not feasible. Documentation must be included as part of the informed consent process for subjects who decline this option.
  • Has a known hypersensitivity to any study treatments (e.g. melphalan, plerixafor).

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): NCT02186418


Contacts
Layout table for location contacts
Contact: Courtney Little 513-354-3864 clinicaltrials@aruvant.com

Locations
Layout table for location information
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
United States, North Carolina
Atrium Health Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Canada, Ontario
University Health Network Not yet recruiting
Toronto, Ontario, Canada, M5G 2N2
Jamaica
Caribbean Institute for Health Research, University of the West Indies Recruiting
Kingston, Jamaica
Sponsors and Collaborators
Aruvant Sciences GmbH
Investigators
Layout table for investigator information
Study Director: Joseph McIntosh, MD Aruvant Sciences GmbH
Layout table for additonal information
Responsible Party: Aruvant Sciences GmbH
ClinicalTrials.gov Identifier: NCT02186418    
Other Study ID Numbers: ARU-1801_Ph1_01
First Posted: July 10, 2014    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aruvant Sciences GmbH:
sickle cell disease
sickle cell anemia
hemoglobinopathies
hematopoietic stem cell
gene transfer
gene therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn