Clinical Trials Register

Summary
EudraCT Number:	2018-002880-25
Sponsor's Protocol Code Number:	LTE15174
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-09-30
Trial 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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2018-002880-25

A.3

Full title of the trial

ATLAS-OLE: An Open-label, Long-term Safety and Efficacy Study of Fitusiran in Patients with Hemophilia A or B, with or without Inhibitory Antibodies to Factor VIII or IX

A.3.1

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

Long-term Safety and Efficacy Study of Fitusiran in Patients with Hemophilia A or B, with or without Inhibitory Antibodies to Factor VIII or IX

A.3.2

Name or abbreviated title of the trial where available

ATLAS-OLE

A.4.1

Sponsor's protocol code number

LTE15174

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1210-0018

A.5.4

Other Identifiers

Name:

IND

Number:

125632

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/186/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genzyme Corporation
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	Genzyme Corporation
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	PPD Global
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	929 North Front Street
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	28401
B.5.3.4	Country	United States
B.5.4	Telephone number	+49 89 578 77 131
B.5.5	Fax number	+49 89 578 77 400
B.5.6	E-mail	Saban.Musoski@ppdi.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/3/14/1297; EU/3/14/1298
D.3 Description of the IMP
D.3.1	Product name	Fitusiran
D.3.2	Product code	SAR439774
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fitusiran
D.3.9.1	CAS number	1609016-97-8
D.3.9.2	Current sponsor code	SAR439774
D.3.9.4	EV Substance Code	SUB130859
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
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	No
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	No
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.IMP: 2
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/3/14/1297; EU/3/14/1298
D.3 Description of the IMP
D.3.1	Product name	Fitusiran
D.3.2	Product code	SAR439774
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fitusiran
D.3.9.1	CAS number	1609016-97-8
D.3.9.2	Current sponsor code	SAR439774
D.3.9.4	EV Substance Code	SUB130859
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
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	No
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	No
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

Hemophilia A or Hemophilia B

E.1.1.1

Medical condition in easily understood language

Hemophilia is an inherited bleeding disorder in which the blood does not clot normally and can result in internal bleeding into the muscles and joints.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060613
E.1.2	Term	Hemophilia A (Factor VIII)
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060614
E.1.2	Term	Hemophilia B (Factor IX)
E.1.2	System Organ Class	100000004850

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

To characterize the long-term safety and tolerability of fitusiran.

E.2.2

Secondary objectives of the trial

To characterize the long-term efficacy of fitusiran as assessed by the frequency of:
- Bleeding episodes,
- Spontaneous bleeding episodes,
- Target joint bleeding episodes.
To characterize the effects of fitusiran on health-related quality of life measures in participants ≥17 years of age.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Age
01. Participant must be at least 12 years of age inclusive, at the time of signing the informed consent

Type of participant and disease characteristics
02. Participants with severe hemophilia A or B who have completed a Phase 3 fitusiran clinical trial

Sex
03. Male
A) There are no contraceptive requirements for this study except where required by local regulations.

Informed Consent
04. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in
this protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

Medical conditions
01. Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional factor concentrate or BPA infusion for postoperative hemostasis

Prior/concomitant therapy
02. Current participation in ITI
03. Current use of factor concentrates or BPAs as regularly administered prophylaxis designed to prevent spontaneous bleeding episodes
04. Use of compounds other than factor concentrates or BPAs for hemophilia treatment

Prior/concurrent clinical study experience
05. Received an investigational drug or device, other than fitusiran, within 30 days of anticipated IMP administration or 5 half-lives of the IMP, whichever is longer
06. Current or prior participation in a gene therapy trial

Diagnostic assessments
07. ALT and/or AST >1.5× upper limit of normal reference range (ULN) for patients who are naïve to fitusiran at study start; ALT and/or AST >5× ULN for patients who were in the fitusiran arm in the parent study.

Other exclusions
08. Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized
09. Any country-related specific regulation that would prevent the participant from entering the study
10. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
11. Participants who are dependent on the Sponsor or Investigator (as defined in section 1.61 of the International Council for Harmonisation (ICH)-Good Clinical Practice (GCP) E6)
12. Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals
13. Any specific situation during study implementation/course that may rise ethics considerations
14. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study

E.5 End points

E.5.1

Primary end point(s)

Incidence, severity, relatedness, and seriousness of AEs, and laboratory assessments.

E.5.1.1

Timepoint(s) of evaluation of this end point

Through duration of the study (up to 55 months)

E.5.2

Secondary end point(s)

Annualized bleeding rate in the treatment period.
Annualized spontaneous bleeding rate in the treatment period.
Annualized joint bleeding rate in the treatment period.
Change in haemophilia quality of life questionnaire for adults physical health score and total score in the treatment period (in participants ≥17 years of age).

E.5.2.1

Timepoint(s) of evaluation of this end point

Through duration of treatment (up to 48 months)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

E.7.1.1

First administration to humans

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)

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Australia

Bulgaria

Canada

China

Denmark

France

Germany

Hungary

India

Ireland

Israel

Italy

Japan

Korea, Republic of

Malaysia

Portugal

Russian Federation

South Africa

Spain

Taiwan

Turkey

Ukraine

United Kingdom

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

Last Patient Last Visit (LPLV)

E.8.9 Initial estimate of the duration of the trial

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)

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)

Yes

F.1.2.1

Number of subjects for this age range:

210

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

244

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)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Argentina

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