Long-term Follow-up of Subjects With Sickle Cell Disease Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector

2024-513901-30-00 Protocol LTF-307 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 3 Nov 2020 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol LTF-307

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 88
Countries 1
Sites 1

Sickle-cell disease

- Evaluate long-term safety of treatment with lovocel (lovotibeglogene autotemcel, also known as bb1111 or LentiGlobin BB305 Drug Product for Sickle Cell Disease) in subjects with sickle cell disease (SCD) - Evaluate long-term efficacy of treatment with bb1111 in subjects with SCD

Key facts

Sponsor
Genetix Biotherapeutics Inc.
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Hemic and Lymphatic Diseases [C15]
Trial duration
3 Nov 2020 → ongoing
Decision date (initial)
2024-06-25
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
bluebird bio, Inc.

External identifiers

EU CT number
2024-513901-30-00
EudraCT number
2019-004266-18
ClinicalTrials.gov
NCT04628585

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic

- Evaluate long-term safety of treatment with lovocel (lovotibeglogene autotemcel, also known as bb1111 or LentiGlobin BB305 Drug Product for Sickle Cell Disease) in subjects with sickle cell disease (SCD)
- Evaluate long-term efficacy of treatment with bb1111 in subjects with SCD

Conditions and MedDRA coding

Sickle-cell disease

VersionLevelCodeTermSystem organ class
21.0 PT 10040644 Sickle cell disease 100000004850

Regulatory references

Plan to share IPD
Yes
EU CT numberTitleSponsor
2012-000695-42 A Phase I/II Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with a Lentiviral beta-A-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/ legal guardian(s)
  2. Treated with drug product for therapy of SCD in a bluebird bio-sponsored clinical study

Exclusion criteria 1

  1. There are no exclusion criteria for this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

  1. The number of subjects with immune-related AEs (e.g., autoimmune disorders, graft-versus-host disease, opportunistic infections, HIV)
  2. The number of subjects with new or worsening hematologic disorders
  3. The number of subjects with new or worsening neurologic disorders
  4. The number of subjects with malignancies

Secondary endpoints 8

  1. Vaso-Occlusive Events Endpoints: The proportion of subjects with complete resolution of severe VOEs (sVOE-CR) over time through Year 15
  2. The proportion of subjects with complete resolution of VOEs (VOE-CR) over time through Year 15
  3. Annualized number of severe VOEs over time through Year 15
  4. Annualized number of VOEs over time through Year 15
  5. Change from parent study baseline in annualized number of severe VOEs over time through Year 15
  6. Hematologic Endpoints: Assessment of the following over time post-drug product infusion through Year 15: − total Hb − non-transfused total Hb − HbS percentage of non-transfused total Hb − HbAT87Q percentage of non-transfused total Hb − non-HbS percentage of non-transfused total Hb
  7. Change from parent study baseline through Year 15 in the following hemolysis markers: absolute reticulocyte count, % reticulocytes/erythrocytes, total bilirubin, indirect bilirubin, haptoglobin, and lactate dehydrogenase
  8. Change from parent study baseline through Year 15 in the following markers of iron stores: serum ferritin and liver iron content

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

LentiGlobin BB305 Drug Product for Sickle Cell Disease

PRD11215938 · Product

Active substance
Lovotibeglogene Autotemcel
Pharmaceutical form
DISPERSION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
0 Other
Max total dose
0 Other
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
BLUEBIRD BIO INC.
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genetix Biotherapeutics Inc.

Sponsor organisation
Genetix Biotherapeutics Inc.
Address
455 Grand Union Boulevard
City
Somerville
Postcode
02145-1446
Country
United States

Scientific contact point

Organisation
Bluebird Bio Inc.
Contact name
Clinical Trial Information

Public contact point

Organisation
Bluebird Bio Inc.
Contact name
Clinical Trial Information

Third parties 9

OrganisationCity, countryDuties
Unisphere Travel Ltd. Inc.
ORG-100043100
Stamford, United States Other
CTI Clinical Trial and Consulting Services Europe GmbH
ORG-100008276
Ulm, Germany Other
Icon Clinical Research Limited
ORG-100008322
Dublin 18, Ireland Laboratory analysis
ProtaGene CGT GmbH
ORG-100041450
Heidelberg, Germany Other
Icon Laboratory Services Inc.
ORG-100037135
Farmingdale, United States Laboratory analysis
Icon Development Solutions LLC
ORG-100012400
Whitesboro, United States Laboratory analysis
Primevigilance Limited
ORG-100027742
Guildford, United Kingdom Code 8
Edetek Inc.
ORG-100045957
Princeton, United States Code 10
Voisin Consulting CH SARL
ORG-100031396
Lausanne, Switzerland Code 12

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 3 1
Rest of world
United States
85

Investigational sites

France

1 site · Ongoing, recruiting
Hopital Necker Enfants Malades
Departement de Biotherapie, 149 Rue De Sevres, 75015, Paris

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2020-11-03 2020-11-03

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 1 file

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-513901-30-00_For publication 4.0

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-05-14 France Acceptable
2024-06-10
2024-06-25
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-12-18 France Acceptable
2024-06-10
2025-12-18
3 NON SUBSTANTIAL MODIFICATION NSM-2 2026-02-12 France Acceptable
2024-06-10
2026-02-12