Long - Term Follow Up of Sickle Cell Disease and Beta-thalassemia Subjects Previously Exposed to BIVV003 or ST-400.

Study Overview
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Brief Summary
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Primary Objectives: Long-term safety of BIVV003 in participants with severe sickle cell disease (SCD) and ST- 400 in participants with transfusion-dependent beta-thalassemia (TDT) Secondary Objectives: Long-term efficacy of the biological treatment effect of BIVV003 in SCD Long-term efficacy of the clinical treatment effect of BIVV003 on SCD-related clinical events Long-term efficacy of the biological treatment effect of ST-400 in TDT Long-term efficacy of the clinical treatment effect of ST-400 in TDT

Detailed Description
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The total study duration is up to 15 years of follow-up post BIVV003 and/or ST-400 infusion.

Official Title
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An Observational Long-term Safety and Efficacy Follow-up Study After Ex-vivo Gene Therapy With BIVV003 in Participants With Severe Sickle Cell Disease (SCD) or With ST-400 in Participants With Transfusion-dependent Beta-thalassemia (TDT) With Autologous Hematopoietic Stem Cell Transplant

Conditions
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Blood and Lymphatic Diseases

Intervention / Treatment
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* Drug: BIVV003
* Drug: ST-400


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received treatment with BIVV003 or ST-400 in one of the parent studies (ACT16222, ST- 400-01) or any future studies with BIVV003 Capable of giving signed informed consent (and if applicable assent) Exclusion Criteria: Unable to comply with study visit schedule or study procedures Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the participant unsuitable for participation in the study The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BIVV003 Cohort<br>All participants treated in parent and future studies with BIVV003 | Drug: BIVV003<br>* Solution for intravenous administration<br>* Other names: SAR445136;|
| ST-400 Cohort<br>All participants treated in parent studies with ST-400 | Drug: ST-400<br>* Solution for intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with serious adverse events and adverse events related to BIVV003 or ST-400, including new malignancy, new incidence or exacerbation of neurologic or rheumatologic or autoimmune or hematologic disorder, or new incidence of infection potentially related to BIVV003 or ST-400 | Up to 15 years | 
| Overall Survival | Duration from first dose of study medication to death | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin levels | Long-term change in levels of hemoglobin F, hemoglobin S and total hemoglobin (BIVV003 cohort), long term change in levels of hemoglobin F and total hemoglobin (ST-400 cohort) | Up to 15 years | 
| Change in hemolysis markers | Long-term change in markers of hemolysis, including reticulocyte count, lactate dehydrogenase, haptoglobin, and serum bilirubin, over time in the BIVV003 cohort | Up to 15 years | 
| Frequency of severe vaso-occlusive crises | Percentage of participants with severe vaso-occlusive crises, including acute pain crisis, acute chest syndrome, priapism, and splenic sequestration, in the BIVV003 cohort | Up to 15 years | 
| Frequency and severity of SCD-related clinical events | Percentage of participants with SCD-related clinical events (e.g., acute renal failure, acute stroke) in the BIVV003 cohort | Up to 15 years | 
| Red blood cell transfusions | Number and total volume of red blood transfusions in the BIVV003 and ST-400 cohorts | Up to 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease (SCD), Beta-thalassemia (TDT)