Clinical Trials Register

Summary
EudraCT Number:	2021-003450-22
Sponsor's Protocol Code Number:	P-105-303
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-10-22
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

Italy - Italian Medicines Agency

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

Sperimentazione di fase 3, randomizzata, in doppio cieco, controllata con placebo, con cross-over, su Posoleucel (ALVR105) per il trattamento dell’infezione da adenovirus in partecipanti adulti e pediatrici che ricevono lo standard di cura in seguito a trapianto allogenico di cellule ematopoietiche

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).

Sperimentazione di fase 3 sulla terapia cellulare Posoleucel per il trattamento dell’infezione da adenovirus in adulti e bambini che ricevono lo standard di cura in seguito a trapianto allogenico di cellule ematopoietiche (cellule responsabili della produzione di cellule ematiche mature nel midollo osseo).

A.3.2

Name or abbreviated title of the trial where available

Phase 3 ALVR105 for AdV Infection following HC Transplantation

Fase 3 ALVR 105 per infezione da AdV dopo trapianto di HC

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
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	Linfociti T allogenici multi-virus specifici che hanno come target il virus BK, il citomegalovirus, il virus dell'herpes umano-6, il virus di Epstein Barr e l'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 injection
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

Infezione da AdV in pazienti pediatrici e adulti allo HCT che ricevono standard di cura

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.

Infezione da Adv in pazienti pediatrici e adulti che hanno ricevuto un trapianto di cellule ematopoietiche (cellule coinvolte nella formazione delle cellule del sangue) e riceventi standard di cura.

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.

Confrontare la percentuale dei partecipanti che presenta clearance della viremia dell’AdV al Giorno 29 fra coloro che hanno ricevuto Posoleucel e SoC, e coloro che hanno ricevuto placebo e SoC.

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)Determinare la percentuale di partecipanti che sviluppa una patologia d’organo da AdV (ad es. malattia delle basse vie respiratorie documentata radiograficamente, cistite emorragica associata ad AdV, epatite grave) o la cui patologia d’organo progredisce entro il Giorno 29.
2)Valutare l’effetto di Posoleucel sulla viremia dell’AdV nell’arco di un periodo di 28 giorni.
3)Determinare la percentuale di partecipanti che sviluppa una patologia d’organo da AdV o la cui patologia d’organo progredisce durante lo studio.
4)Determinare la percentuale di partecipanti che consegue una viremia dell’AdV <400 copie/ml di AdV DNA.
5)Valutare l’effetto di Posoleucel sul tempo diclearance della viremia dell’AdV.
6)Valutare la percentuale di partecipanti che presenta recidiva di viremia (¿¿10.000 copie/ml di DNA dell’AdV) e/o patologia d’organo durante lo studio .
7)Valutare la percentuale di partecipanti senza patologia d’organo al Giorno 29 e alla fine dello studio.

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. Soggetti ambosessi di età >1 anno.
2. Sottoposti a trapianto di cellule allogeniche (comprese cellule del cordone ombelicale) ¿¿21 giorni prima della randomizzazione e hanno dimostrato attecchimento con una conta assoluta dei neutrofili >500/mm3, E presentano uno dei seguenti:
a. Viremia del DNA AdV ¿¿10.000 copie/ml allo screening, OPPURE
b. Due risultati consecutivi e in aumento della viremia del DNA AdV ¿¿1.000 copie/ml allo screening, E
i. conta assoluta dei linfociti <180/mm3
, OPPURE
ii. sottoposti a deplezione delle cellule T.
3. I soggetti ambosessi in età fertile che hanno rapporti eterosessuali devono accettare di utilizzare metodi contraccettivi come descritto nell’Appendice 5 di questo protocollo e devono evitare di donare sperma od ovuli per almeno 90 giorni dopo il completamento del trattamento.
4. Disponibilità e capacità di esprimere il consenso informato per iscritto.
5. Presentano una corrispondenza del tipo di antigene leucocitario umano (HLA) con almeno 1 linea VST di Posoleucel adeguatamente compatibile e disponibile per l’infusione.

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. GVHD acuta di grado >2 (vedere l’Appendice 6 per informazioni sulla classificazione e sulla gravità della GVHD acuta).
2. Terapia in corso con corticosteroidi sistemici ad alto dosaggio (ovvero, dose di prednisone >0,5 mg/kg/giorno o equivalente).
3. Presentano uno dei seguenti parametri di laboratorio allo screening:
a. Livelli sierici di aspartato aminotransferasi e alanina aminotransferasi ¿¿5 volte il limite superiore dell’intervallo normale (ULN), OPPURE
b. Livelli sierici di bilirubina diretta ¿¿3 volte l’ULN.
Eccezione: i pazienti con aumenti di questi parametri di laboratorio possono essere inclusi se questi aumenti sono attribuiti all’epatite da AdV e non sono considerati attribuibili ad altre eziologie.
4. Recidiva di tumore maligno primario o di qualsiasi altro tumore maligno attivo, a eccezione del tumore cutaneo diverso dal melanoma.
5. Diarrea di grado 4 (vale a dire, conseguenze potenzialmente letali con intervento urgente indicato) indipendentemente dall’attribuzione in corso o nei 7 giorni precedenti la
randomizzazione.
6. Infezione virale (diversa da quella da AdV), batterica o fungina non controllata, che causa instabilità emodinamica oppure evidenza radiologica o di laboratorio attribuibile al peggioramento della malattia.
7. Necessità di frazione di ossigeno inspirato >0,5 per mantenere la saturazione arteriosa di ossigeno >90% (tramite pulsossimetria) o necessità di ventilazione meccanica.
8. Precedente terapia con globulina anti-timociti, alemtuzumab (Campath®) o altri anticorpi monoclonali immunosoppressivi che hanno come bersaglio le cellule T nei 28 giorni precedenti la randomizzazione.
9. Precedente infusione di linfociti da donatore o infusione di cellule staminali CD34+ nei 21 giorni precedenti la randomizzazione.
Si applicano altri criteri definiti dal protocollo

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.

Percentuale di partecipanti con viremia non rilevabile (minore del limite inferiore di determinazione quantitativa [LLOQ]) al Giorno 29.

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline, Day 29

Basale, giorno 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) Percentuale di partecipanti con progressione della malattia o mortalità senza recidiva entro il Giorno 29.
2)Percentuale di partecipanti con viremia non rilevabile (inferiore all’LLOQ) al Giorno 29 nei partecipanti senza malattia da AdV allo screening.
3)Percentuale di partecipanti con viremia non rilevabile (inferiore all’LLOQ) al Giorno 29 nei partecipanti con malattia da AdV allo screening
4)Area sotto la curva concentrazione-tempo (AAUC) mediata nel tempo per la viremia plasmatica dell’AdV (log10 copie/ml di AdV DNA) analizzata mediante reazione a catena della polimerasi quantitativa (qPCR) fino al Giorno 29 per tutti i partecipanti.
5)AUC per la viremia plasmatica dell’AdV (log10 copie/ml di AdV DNA) analizzata mediante qPCR fino al Giorno 29 per i partecipanti senza patologia d’organo allo screening
6)Percentuale di partecipanti con progressione della malattia o mortalità senza recidiva durante lo studio.
7)Percentuale di partecipanti che consegue una viremia dell’AdV <400 copie/ml di AdV DNA al Giorno 29.
8)Tempo necessario per arrivare a una viremia di AdV non rilevabile (inferiore all’LLOQ).
9)Percentuale di partecipanti con recidiva della malattia da AdV durante lo studio tra i partecipanti che presentavano una clearance della viremia dell’AdV (prima di qualsiasi cross-over).
10)Percentuale di partecipanti senza patologia d’organo al Giorno 29 e alla fine dello studio

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, giorno 29
2,3) basale, giorno 29
4,5) Giorno 29
6) continuo / fine studio
7) Giorno 29
8,9) settimanale
10) basale, giorno 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

Information not present in EudraCT

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

United States

Italy

Spain

Sweden

United Kingdom

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.1.1.1

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