Kliiniset tutkimukset Nct sivu

Summary
EudraCT Number:2018-002880-25
Sponsor's Protocol Code Number:LTE15174
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Prematurely Ended
Date on which this record was first entered in the EudraCT database:2019-04-11
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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2018-002880-25
A.3Full 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
ATLAS-OLE: Estudio abierto de la seguridad y la eficacia a largo plazo de fitusirán en pacientes con hemofilia A o B, con o sin anticuerpos inhibidores de los factores VIII o IX
A.3.1Title 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
Estudio de la seguridad y la eficacia a largo plazo de fitusirán en pacientes con hemofilia A o B, con o sin anticuerpos inhibidores de los factores VIII o IX
A.3.2Name or abbreviated title of the trial where available
ATLAS-OLE
ATLAS-OLE
A.4.1Sponsor's protocol code numberLTE15174
A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1210-0018
A.5.4Other Identifiers
Name:INDNumber:125632
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorGenzyme Corporation
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportGenzyme Corporation
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationPPD Global
B.5.2Functional name of contact pointProject Management
B.5.3 Address:
B.5.3.1Street Address929 North Front Street
B.5.3.2Town/ cityWilmington
B.5.3.3Post code28401
B.5.3.4CountryUnited States
B.5.4Telephone number900834223
B.5.6E-mailRegistroEspanolDeEstudiosClinicos@druginfo.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/14/1297; EU/3/14/1298
D.3 Description of the IMP
D.3.1Product nameFitusiran
D.3.2Product code SAR439774
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNfitusiran
D.3.9.1CAS number 1609016-97-8
D.3.9.2Current sponsor codeSAR439774
D.3.9.4EV Substance CodeSUB130859
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number100
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another 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.1.1Medical condition(s) being investigated
Hemophilia A or Hemophilia B
Hemofilia A o Hemofilia B
E.1.1.1Medical 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.
La hemofilia es un trastorno hemorrágico hereditario en el que la sangre no coagula normalmente y puede dar lugar a sangrado interno en los músculos y las articulaciones
E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10060613
E.1.2Term Hemophilia A (Factor VIII)
E.1.2System Organ Class 100000004850
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10060614
E.1.2Term Hemophilia B (Factor IX)
E.1.2System Organ Class 100000004850
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To characterize the long-term safety and tolerability of fitusiran.
Caracterizar la seguridad y la tolerabilidad de fitusirán a largo plazo
E.2.2Secondary 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.
Caracterizar la eficacia a largo plazo de fitusirán, evaluada mediante la frecuencia de:
•Episodios hemorrágicos.
•Episodios hemorrágicos espontáneos.
•Episodios hemorrágicos en las articulaciones diana.
Caracterizar los efectos de fitusirán sobre las mediciones de la calidad de vida relacionada con la salud en participantes ≥ 17 años.
E.2.3Trial contains a sub-study No
E.3Principal 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.
Únicamente podrán ser incluidos en el estudio los participantes que cumplan todos los criterios siguientes:

Edad
01. El participante debe tener al menos 12 años, inclusive, en el momento de firmar el consentimiento informado.

Tipo de participante y características de la enfermedad
02. Participantes con hemofilia A o B grave que hayan completado un ensayo clínico en fase 3 de fitusirán.

Sexo
03. Varones.
A) En este estudio no hay requisitos sobre anticonceptivos, salvo cuando lo exija la normativa local.

Consentimiento informado
04. Capaz de otorgar el consentimiento informado firmado, lo que incluye el cumplimiento de los requisitos y restricciones enumerados en el DCI y en este protocolo. En los países donde la mayoría de edad legal esté fijada a partir de los 18 años, el representante legal del participante también deberá firmar un DCI específico.
E.4Principal 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
Se excluirá del estudio a los participantes que cumplan alguno de los criterios siguientes:

Enfermedades
01. Finalización de una intervención quirúrgica en los 14 días anteriores a la selección o tratamiento actual con infusión adicional de concentrados de factores o agentes de puenteo con fines de hemostasia postoperatoria.

Tratamiento previo y concomitante
02. Participación actual en inducción de inmunotolerancia (IIT).
03. Uso actual de concentrados de factores o agentes de puenteo como tratamiento profiláctico regular destinado a prevenir episodios hemorrágicos espontáneos.
04. Uso de compuestos distintos de concentrados de factores o agentes de puenteo para el tratamiento de la hemofilia.

Experiencia previa y concomitante en estudios clínicos
05. Recepción de un fármaco o dispositivo en investigación, distinto de fitusirán, en los 30 días previos a la administración prevista del PEI o el equivalente a 5 semividas del PEI, lo que suponga más tiempo.
06. Participación actual o previa en un ensayo de terapia génica.

Evaluaciones diagnósticas
07. ALT y/o AST > 1,5 veces el límite superior del intervalo de referencia normal (LSN) en los pacientes no tratados previamente con fitusirán al comienzo del estudio; ALT y/o AST > 5 veces el LSN en los pacientes que estaban en el grupo de fitusirán en el estudio original.

Otras exclusiones
08. Personas alojadas en un establecimiento sanitario por disposición reglamentaria o legal; reclusos o participantes internados por dictamen legal.
09. Cualquier ley específica del país que impida la inclusión del participante en el estudio
10. Participantes que no sean aptos para participar, sea cual sea el motivo, a juicio del investigador, incluida la presencia de dolencias médicas o clínicas, o participantes con riesgo potencial de incumplimiento de los procedimientos del estudio.
11. Participantes que dependen del promotor o del investigador (según se define en la sección 1.61 de la Buena práctica clínica (BPC) E6) de la Conferencia Internacional de Armonización (ICH).
12. Participantes que sean empleados del centro del estudio clínico o de otras personas implicadas directamente en la realización del estudio, o familiares inmediatos de dichas personas.
13. Cualquier situación específica durante la realización/transcurso del estudio que pueda suscitar dudas éticas.
14. Sensibilidad a cualquiera de los fármacos o las intervenciones del estudio, o de sus componentes, u otras alergias que, en opinión del investigador, contraindiquen la participación en el estudio.
E.5 End points
E.5.1Primary end point(s)
Incidence, severity, relatedness, and seriousness of AEs, and laboratory assessments.
Incidencia, intensidad, relación causal y gravedad de los AA y evaluaciones analíticas
E.5.1.1Timepoint(s) of evaluation of this end point
Through duration of the study (up to 55 months)
Durante toda la duración del estudio (hasta 55 meses)
E.5.2Secondary 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).
Tasa anualizada de hemorragias durante el período de tratamiento.
Tasa anualizada de hemorragias espontáneas durante el período de tratamiento.
Tasa anualizada de hemorragias articulares durante el período de tratamiento.
Variación de la puntuación de salud física y la puntuación total del cuestionario de calidad de vida en la hemofilia para adultos durante el período de tratamiento (en participantes ≥ 17 años).
E.5.2.1Timepoint(s) of evaluation of this end point
Through duration of treatment (up to 48 months)
Durante toda la duración del tratamiento (hasta 48 meses)
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis Yes
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
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 No
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA40
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions 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.8.7Trial 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)
Última visita del último paciente (UVUP)
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years6
E.8.9.1In the Member State concerned months7
E.8.9.1In the Member State concerned days3
E.8.9.2In all countries concerned by the trial years6
E.8.9.2In all countries concerned by the trial months7
E.8.9.2In all countries concerned by the trial days3
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 22
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 22
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 210
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 12
F.2 Gender
F.2.1Female No
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state6
F.4.2 For a multinational trial
F.4.2.1In the EEA 100
F.4.2.2In 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
Ninguno
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2019-04-26
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2019-04-11
P. End of Trial
P.End of Trial StatusPrematurely Ended

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa