Clinical Trials Register

Summary
EudraCT Number:	2011-001953-10
Sponsor's Protocol Code Number:	ALD-102
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-06-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2011-001953-10

A.3

Full title of the trial

A phase 2/3 study of the efficacy and safety of hematopoietic stem cells transduced with Lenti D lentiviral vector for the treatment of childhood cerebral adrenoleukodystrophy (CCALD)

Étude de phase 2/3 visant à évaluer l’efficacité et la sécurité de cellules souches hématopoïétiques transduites avec un vecteur lentiviral Lenti-D dans le traitement de l’adrénoleucodystrophie cérébrale infantile (ALD-CI)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical study to assess the efficacy and safety of gene therapy for the treatment of childhood cerebral adrenoleukodystrophy

A.4.1

Sponsor's protocol code number

ALD-102

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/119/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	bluebird bio, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	bluebird bio, Inc (with its wholly owned subsidiary bluebird bio France)
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NUVISAN France SARL
B.5.2	Functional name of contact point	Patrice MARCHAND
B.5.3	Address:
B.5.3.1	Street Address	18-20 rue Pasteur
B.5.3.2	Town/ city	Le Kremlin Bicêtre
B.5.3.3	Post code	94278
B.5.3.4	Country	France
B.5.4	Telephone number	33(0) 145 15 40 82
B.5.5	Fax number	33 (0) 145 15 40 61
B.5.6	E-mail	patrice.marchand@nuvisan.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/12/1003
D.3 Description of the IMP
D.3.1	Product name	Lenti-D Drug Product
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Yes
D.3.11.3.5.1	CAT classification and reference number	Classification: Gene Therapy Medicinal Product Reference Number: EMA/CAT/988313/2011
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Childhood Cerebral Adrenoleukodystrophy (CCALD)

E.1.1.1

Medical condition in easily understood language

See above.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10051260
E.1.2	Term	Adrenoleukodystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Evaluate the efficacy of Lenti-D Drug Product in subjects with CCALD.
• Evaluate the safety of Lenti-D Drug Product in subjects with CCALD.

E.2.2

Secondary objectives of the trial

Not Applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/IEC and with local requirements.)
2.Boys aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.
3.Active cerebral ALD as defined by:
a.Elevated plasma VLCFA levels, and
b.Active CNS disease established by central radiographic review of brain MRI demonstrating
i.Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
ii.Gadolinium enhancement on MRI of demyelinating lesions.
4.NFS ≤ 1 .

E.4

Principal exclusion criteria

1.Receipt of an allogeneic transplant or gene therapy.
2.Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygote).
3.Use of statins, Lorenzo’s Oil, or dietary regimens used to lower VLCFA levels. Note: subjects must discontinue use of these medications at time of consent.
4.Receipt of an investigational study drug or procedure within 3 months before Screening that might counfound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study .
5.Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
6.Hematological compromise as evidenced by:
a.Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm3,
b.Platelet count < 100,000 cells/mm3, or
c.Hemoglobin < 10 g/dL.
d.Uncorrected bleeding disorder.
7.Hepatic compromise as evidenced by:
a.Aspartate transaminase (AST) value > 2.5× the upper limit of normal (ULN) or
b.Alanine transaminase (ALT) value > 2.5×ULN
c.Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert’s Syndrome and the subject is otherwise stable
8.Renal compromise as evidenced by:
a.Abnormal renal function (creatinine clearance < 50 mL/min)
9.Cardiac compromise as evidenced by:
a.Left ventricular ejection fraction < 40%
10.Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal syndrome, and familial adenomatous polyposis).
11.Clinically significant active bacterial, viral, fungal, or parasitic or prion assiociated infections.
12.Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1, HIV 2), hepatitis B, hepatitis C, or human T lymphotrophic virus 1 (HTLV 1). (Note that subjects who have been vaccinated against hepatitis B [hepatitis B surface antibody-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core antibody] are eligible. Also note that subjects who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load by quantitative polymerase chain reaction [qPCR].)
13.Any clinically significant cardiovascular or pulmonary, or other disease or condition that would be contraindicated for any of the other study procedures.

E.5 End points

E.5.1

Primary end point(s)

Assessment of the proportion of subjects who have no Major Functional Disabilities (MFDs) as determined by key measures in the Neurological Function Score (NFS).

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months (± 2 months) post-transplant

E.5.2

Secondary end point(s)

Secondary efficacy endpoints are:
•Change from Baseline in Loes score
•Change from Baseline in NFS.
•Proportion of subjects who demonstrate resolution of gadolinium positivity on MRI (i.e. who are gadolinium negative).
•Proportion of subjects who maintain an NFS less than or equal to 4 and do not increase their score by 3 points or more.
•Proportion of subjects who maintain a Loes score less than or equal to 9 or do not increase their score by 6 points or more.
MFD-free survival
Overall survival

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months (± 2 months) post-transplant

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of ALD-102 study, subjects will be followed for long term safety and efficacy under a separate protocol (LTF-303; EudraCT number: 2013-002245-11) for 13 years. Thus, subjects will be followed for a total of 15 years post-transplant.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-07-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-03-26

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