Clinical Trials Register

Summary
EudraCT Number:	2021-003450-22
Sponsor's Protocol Code Number:	P-105-303
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:	2021-12-22
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

Spain - AEMPS

A.2

EudraCT number

2021-003450-22

A.3

Full title of the trial

Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

Ensayo de fase 3, aleatorizado, doble ciego, controlado con placebo y cruzado de posoleucel (ALVR105) para el tratamiento de la infección por adenovirus en participantes pediátricos y adultos que reciben la asistencia habitual tras un alotrasplante de progenitores hematopoyéticos

A.3.1

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

Phase 3 study of Posoleucel cell therapy for the treatment of adenovirus infection in children and adults receiving standard of care following transplantation of hematopoietic cells (cells responsible for the production of mature blood cells in bone marrow).

Estudio de fase 3 de terapia celular Posoleucel para el tratamiento de la infección por adenovirus en niños y adultos que reciben asistencia habitual después del trasplante de células hematopoyéticas (células responsables de la producción de células sanguíneas maduras en la médula ósea)

A.4.1

Sponsor's protocol code number

P-105-303

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AlloVir, 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	AlloVir, Inc.
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	AlloVir, Inc.
B.5.2	Functional name of contact point	Clinical Trials Information Line
B.5.3	Address:
B.5.3.1	Street Address	Kirby Grove, 2925 Richmond Ave, Suite 1200
B.5.3.2	Town/ city	Houston, Texas
B.5.3.3	Post code	77098
B.5.3.4	Country	United States
B.5.6	E-mail	ClinicalTrials@allovir.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/3/20/2260
D.3 Description of the IMP
D.3.1	Product name	Posoleucel
D.3.2	Product code	ALVR105
D.3.4	Pharmaceutical form	Dispersion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Posoleucel
D.3.9.2	Current sponsor code	Viralym-M (ALVR105)
D.3.9.3	Other descriptive name	Allogeneic multi-virus specific T lymphocytes targeting BK Virus, cytomegalovirus, human herpes virus-6, Epstein Barr virus and adenovirus
D.3.9.4	EV Substance Code	SUB197084
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000000
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Dispersion for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

AdV infection in pediatric and adult allo HCT recipients receiving standard of care

Infección por AdV en niños y adultos receptores de un aloTPH que reciban la asistencia habitual.

E.1.1.1

Medical condition in easily understood language

Adenovirus infection in child and adult patients who received hematopoietic cell transplant (cells involved in the formation of blood cells) and are receiving standard of care treatment.

Infección por AdV en pacientes niños y adultos que recibieron trasplante de células hematopoyéticas (células involucradas en la formación de células sanguíneas) y están recibiendo asitencia habitual.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10060931
E.1.2	Term	Adenovirus infection
E.1.2	System Organ Class	10021881 - Infections and infestations

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 compare the percent of participants who have clearance of AdV viremia at Day 29 in participants receiving posoleucel and SoC to that in participants receiving placebo and SoC.

Comparar el porcentaje de participantes con eliminación de la viremia por AdV el día 29 entre los participantes que reciben posoleucel y asistencia habitual y los que reciben placebo y asistencia habitual.

E.2.2

Secondary objectives of the trial

1) To determine the percent of participants who develop target organ AdV disease or whose target organ disease progresses by Day 29.

2) To evaluate the effect of posoleucel on AdV viremia over a 28-day period.

3) To determine the percent of participants who develop target organ AdV disease or whose target organ disease progresses during the study.

4) To determine the percentage of participants who achieve AdV viremia <400 copies/mL AdV DNA.

5) To assess the effect of posoleucel on time to clearance of AdV viremia.

6) To evaluate the proportion of participants who have recurrence of viremia (≥10,000 copies/mL AdV DNA) and/or target organ disease during the study

7) To evaluate the proportion of participants who are target organ disease-free at Day 29 and at the end of the study.

1) Determinar el porcentaje de participantes que desarrollan enfermedad por AdV de órganos diana o cuya enfermedad de órganos diana progresa para el día 29.
2) Evaluar el efecto de posoleucel sobre la viremia por AdV durante un período de 28 días.
3) Determinar el porcentaje de participantes que desarrollan enfermedad por AdV de órganos diana o cuya enfermedad de órgano diana progresa durante el estudio
4) Determinar el porcentaje de participantes que logran una viremia por AdV <400 copias/ml de ADN de AdV.
5) Evaluar el efecto de posoleucel sobre el tiempo hasta la eliminación de la viremia por AdV
6) Evaluar la proporción de participantes que presentan recurrencia de la viremia (≥10 000 copias/ml de ADN de AdV) o enfermedad de órgano diana durante el estudio
7) Evaluar la proporción de participantes sin enfermedad de órgano diana el día 29 y al final del estudio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female >1 year of age.
2. Has undergone allogeneic (including umbilical cord) cell transplantation ≥21 days prior to randomization and has demonstrated engraftment with an absolute neutrophil count >500/mm3, AND has one of the following:

a. AdV viremia DNA ≥10,000 copies/mL at screening, OR
b. Two consecutive and rising AdV viremia DNA results of ≥1,000 copies/mL at screening, AND
i. has absolute lymphocyte count <180/mm3, OR
ii. has received T cell depletion.

3. Males and females of childbearing potential who engage in heterosexual intercourse must agree to use contraception as detailed in Appendix 5 of this protocol and refrain from donating sperm or eggs for at least 90 days after treatment completion.
4. Willing and able to provide signed informed consent.
5. Has an HLA type matching with at least 1 suitably matched and available posoleucel VST line for infusion.

1. Paciente de cualquier sexo con una edad >1 año.
2. Haber recibido un alotrasplante de células (incluido cordón umbilical) ≥21 días antes de la aleatorización y presentar injerto prendido demostrado por un recuento absoluto de neutrófilos >500/mm3 Y presencia de una de las circunstancias siguientes:
a. ADN de viremia por AdV ≥10 000 copias/ml en la selección; O
b. dos resultados consecutivos y crecientes del ADN de viremia por AdV ≥1000 copias/ml en la selección; Y
i. tener un recuento absoluto de linfocitos <180/mm3; O
ii. haber recibido depleción de linfocitos T.
3. Los varones y las mujeres en edad fértil que mantengan relaciones heterosexuales deberán comprometerse a utilizar métodos anticonceptivos tal como se detalla en el Apéndice 5 de este protocolo y a abstenerse de donar esperma u óvulos durante al menos 90 días después de finalizar el tratamiento.
4. Disposición y capacidad para otorgar el consentimiento informado firmado.
5. Tener un tipo de HLA compatible con al menos 1 línea de VST de posoleucel adecuada y disponible para infusión

E.4

Principal exclusion criteria

1. Grade >2 acute GVHD (see Appendix 6 for information on acute GVHD grading and
severity).
2. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
3. Has either of the following laboratory parameters at screening:
a. Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times the
upper limit of normal (ULN), OR
b. Direct bilirubin serum levels ≥3 times the ULN.

4. Relapse of primary malignancy, or any other active malignancy, except for non-melanoma skin cancer.
5. Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated) regardless of attribution ongoing or within 7 days prior to randomization.
6. Uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to hemodynamic instability or radiologic or laboratory evidence attributable to worsening disease.
7. Requirement for fraction of inspired oxygen >0.5 to maintain arterial oxygen saturation >90% (via pulse oximetry) or need for mechanical ventilation.
8. Prior therapy with anti-thymocyte globulin, alemtuzumab (Campath®), or other immunosuppressive T cell monoclonal antibodies within 28 days prior to randomization.
9. Prior donor lymphocyte infusion or CD34+ stem cell infusion within 21 days prior to randomization.

Other protocol-defined criteria apply.

1. EICH aguda de grado >2 (véase el Apéndice 6 para obtener información sobre la clasificación y la gravedad de la EICH aguda).
2. Tratamiento en curso con corticosteroides sistémicos en dosis altas (dosis de prednisona >0,5 mg/kg/día o equivalente).
3. Presencia de cualquiera de los siguientes parámetros analíticos en la selección:
a. concentraciones séricas de aspartato aminotransferasa y alanina aminotransferasa ≥5 veces el límite superior de la normalidad (LSN); O
b. concentración sérica de bilirrubina directa ≥3 veces el LSN.

4. Recidiva de una neoplasia maligna primaria o de cualquier otra neoplasia maligna activa, excepto cáncer de piel distinto del melanoma.
5. Diarrea de grado 4 (es decir, consecuencias potencialmente mortales con indicación de intervención urgente) con independencia de la atribución en curso o en los 7 días previos a la aleatorización.
6. Infección vírica (distinta de la causada por AdV), bacteriana o micótica no controlada que provoque inestabilidad hemodinámica o signos radiológicos o analíticos atribuibles a un empeoramiento de la enfermedad.
7. Se requiere una fracción de oxígeno inspirado >0,5 para mantener una saturación de oxígeno arterial >90 % (mediante pulsioximetría) o se necesita ventilación mecánica.
8. Tratamiento previo con globulina antitimocítica, alemtuzumab (Campath®) u otros anticuerpos monoclonales inmunodepresores de linfocitos T en los 28 días previos a la aleatorización.
9. Infusión previa de linfocitos de donante o de células progenitoras CD34+ en los 21 días previos a la aleatorización.

Se aplican otros criterios definidos por el protocolo.

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants with undetectable viremia (less than lower limit
of quantitation [LLOQ]) at Day 29.

Proporción de participantes con viremia indetectable (por debajo del límite inferior de cuantificación [LIC]) el día 29.

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline, Day 29

Valor basal, Día 29

E.5.2

Secondary end point(s)

1) Proportion of participants with disease progression or non-relapse mortality by Day 29.

2) Proportion of participants with undetectable viremia (less than LLOQ) at Day 29 in participants without AdV disease at screening.

3) Proportion of participants with undetectable viremia (less than LLOQ) at Day 29 in participants with AdV disease at screening.

4) Time-averaged area under the concentration-time curve (AAUC) for plasma AdV viremia (log10 copies/mL AdV DNA) as assayed by quantitative polymerase chain reaction (qPCR) through Day 29 for all participants.

5) AAUC for plasma AdV viremia (log10 copies/mL AdV DNA) as assayed by qPCR through Day 29 for participants with no target organ disease at screening.

6) Proportion of participants with disease progression or non-relapse mortality during the study.

7) Proportion of participants who achieve AdV viremia <400 copies/mL AdV DNA at Day 29.

8) Time to undetectable AdV viremia (less than LLOQ).

9) Proportion of participants with AdV disease recurrence during the study among participants who had clearance of AdV viremia (prior to any cross-over)

10) Proportion of participants who are target organ disease-free at Day 29 and at the end
of the study.

1) Proporción de participantes con progresión de la enfermedad o mortalidad sin recidiva para el día 29.
2) Proporción de participantes con viremia indetectable (inferior al LIC) el día 29 en los participantes sin enfermedad por AdV en la selección
3) Proporción de participantes con viremia indetectable (inferior al LIC) el día 29 en los participantes con enfermedad por AdV en la selección.
4) Área bajo la curva de concentracióntiempo promediada por el tiempo (AAUC) de la viremia por AdV en plasma (log10 copias/ml de ADN de AdV) determinada mediante reacción en cadena de la polimerasa cuantitativa (PCRq) hasta el día 29 para todos los participantes
5) El AAUC de la viremia por AdV en plasma (log10 copias/ml de ADN de AdV) determinada mediante PCRq hasta el día 29 para los participantes sin enfermedad de órgano diana en la selección.
6) Proporción de participantes con progresión de la enfermedad o mortalidad sin recidiva durante el estudio.
7) Proporción de participantes que logran una viremia por AdV <400 copias/ml de ADN de AdV el día 29.
8) Tiempo hasta viremia por AdV indetectable (inferior al LIC).
9) Proporción de participantes con recurrencia de la enfermedad por AdV durante el estudio entre los participantes que presentaron eliminación de la viremia por AdV.
10) Proporción de participantes sin enfermedad de órgano diana el día 29 y al final del estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) continuous, Day 29
2,3) baseline, Day 29
4,5) Day 29
6) continuous / end of study
7) Day 29
8,9) weekly
10) baseline, Day 29, EoT

1) continuo, día 29
2,3) valor basal, día 29
4,5) Día 29
6) continuo / fin de estudio
7) Día 29
8,9) semanal
10) valor basal, día 29, EoT

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

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

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

UVUS

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

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

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

Yes

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.4.1

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)

standard of care

asistencia habitual

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

2022-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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