Adenovirus InfectionPhase 3NCT05179057

Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

A Phase 3 study testing Posoleucel in people with Adenovirus Infection, run by AlloVir at 47 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC). Read more about this study

Who is it for?: Any age
Conditions the study is for: Adenovirus Infection
What is being tested?: Posoleucel
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 57 participants
Where: 47 sitesin 6 countries
Study dates: 26 Apr 2022to 31 Jan 2024
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Undergone allogeneic cell transplantation ≥21 days prior to dosing
Meet one of the below criteria:
AdV viremia DNA ≥10,000 copies/mL, OR
AdV viremia DNA results of ≥1,000 copies/mL, AND
has absolute lymphocyte count <180/mm3, OR
has received T cell depletion OR
had a cord blood transplant.

Who cannot join

Grade 3 or higher acute GVHD
Ongoing therapy with high-dose systemic corticosteroids
Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
Pregnant or lactating female unwilling to discontinue nursing prior to randomization
History of severe prior reactions to blood product transfusions
NOTE: Other protocol-defined inclusion/exclusion criterion may apply.

Trial locations and contacts

47 sites in 6 countries.

Country

City, postcode or hospital

47 sites in 6 countries

United States23 sites

Children's Hospital Colorado - Center for Cancer and Blood Disorders
Aurora, Colorado, 80045
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
University of Texas Southwestern
Dallas, Texas, 75390
City of Hope
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida (UF) - Gainesville
Gainesville, Florida, 32611
MD Anderson Cancer Center
Gilbert, Arizona, 85234
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
New York Presbyterian Hospital
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Lucile Packard Children's Hospital - Stanford University
Palo Alto, California, 94303
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Intermountain HealthCare - Primary Children's Hospital
Salt Lake City, Utah, 81432
University of California, San Diego - Rady Children's Hospital
San Diego, California, 92123
Seattle Children's Hospital
Seattle, Washington, 98101
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010

Other trials in United States

Italy8 sites

IRCCS Ospedale San Raffaele
Milan, 20132
Fondazione IRCCS San Gerardo dei Tintori
Monza, 20900
A.O.R.N. Santobono-Pausilipon
Naples, 80123
Azienda Ospedaliera di Padova
Padova, 35128
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Ospedale Pediatrico Bambino Gesù
Roma, 165
Ospedale Regina Margherita
Torino, 10126
Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
Verona, 1-37126

Other trials in Italy

United Kingdom8 sites

Birmingham Children's Hospital
Birmingham, B4 6NH
Bristol Royal Hospital for Children
Bristol, BS2 8BJ
Royal Hospital for Children - Glasgow
Glasgow, G51 4TF
University College London Hospital
London, NW1 2PG
St. Mary's Hospital, Paddington
London, W2 1NY
Great Ormond Street Hospital for Children
London, WC1n 3JH
Royal Manchester Children's Hospital
Manchester, M13 9WL
Sheffield Children's NHS Foundation Trust
Sheffield, S10 2TH

Other trials in United Kingdom

Spain3 sites

Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politecnic La Fe
Valencia, 46026

Other trials in Spain

Sweden3 sites

Sahlgrenska University Hospital
Gothenburg, 41685
Skane University Hospital Lund
Lund, 221 85
Karolinska University Hospital
Solna, 171 64

Other trials in Sweden

Canada2 sites

CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: 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

This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).

Read the detailed description

During the period of immune recovery after allogeneic hematopoietic cell transplant (allo-HCT), viral infections and reactivations, including those with AdV, are an important cause of morbidity and mortality. Progression to AdV disease is associated with significant morbidity and mortality rates. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will assess the safety and efficacy of Posoleucel for the treatment of AdV infection in pediatric and adult allo-HCT recipients receiving SoC.

Conditions: Adenovirus Infection
Being tested: Posoleucel, Placebo
Keywords: Allogeneic Hematopoietic Cell Transplant, Adenoviremia, Adenovirus, Stem Cell Transplant, Posoleucel, ALVR105, Bone Marrow Transplant
Medical subject headings: Adenoviridae Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PosoleucelDrug
Administered as 2-4 milliliter infusion, visually identical to placebo
PlaceboDrug
Administered as 2-4 milliliter infusion, visually identical to Posoleucel

Study groups in NCT05179057
Study group	Role	What they receive
Posoleucel + SoC	Experimental	Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria Receives: Drug: Posoleucel
Placebo + SoC	Placebo comparator	Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Undetectable Adenovirus Infection
Viral load of adenovirus was measured at the central laboratory using quantitative polymerase chain reaction (qPCR) from blood and stool samples at each study visit and on Day 29 from a nasopharyngeal swab. There was a 14-day window for participants who crossed over from posoleucel to placebo; and for participants who crossed over from placebo to posoleucel, the pre-dose cross-over Day 1 viral load was used. Participants missing the primary endpoint but having undetectable viremia before Day 29 and after Day 43 were imputed as successes. Undetectable adenovirus viremia was less than the lower limit of quantification (LLOQ).
Measured: Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included acute or chronic graft versus host disease, cytokine release syndrome, infusion-related reactions, and graft failure or rejection. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.
Measured: Up to 34 weeks

Secondary outcomes (5)

Number of Participants With Overall Disease Progression
Measured: From Day 29 up to Week 10
Area Under the Curve (AUC) Adenovirus Viral Load
Measured: Pre-dose and Day 29
Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29
Measured: Day 29
Time to Undetectable Adenovirus Viremia (Less Than LLOQ)
Measured: Pre-dose to 34 weeks
Number of Participants With Adenovirus Disease Recurrence
Measured: 34 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Apr 202231 Jan 2024

First posted5 Jan 2022
Study start26 Apr 2022
Primary completion31 Jan 2024
Study completion31 Jan 2024

Why it stopped: Study discontinued as DSMB determined it was futile. No safety concerns were noted.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Adenovirus InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study with option for blinded crossover to assess the safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in pediatric and adult recipients of HCT with AdV infections receiving SoC.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05179057
Sponsor's protocol ID: P-105-303
Status last verified: Apr 2024
First submitted: 17 Dec 2021
Last updated: 8 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.
PubMed 38597860

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
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RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingObservational study
Viral Infections in Healthy and Immunocompromised Hosts
Anogenital Herpes, COVID-19
RecruitingPhase 2
Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection
Adenovirus, Primary Immune Deficiency Disorder
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia

All Adenovirus Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT05179057
Acronym / sponsor ID: P-105-303
Conditions: Adenovirus Infection
Keywords: Allogeneic Hematopoietic Cell Transplant, Adenoviremia, Adenovirus, Stem Cell Transplant, Posoleucel, ALVR105, Bone Marrow Transplant
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study discontinued as DSMB determined it was futile. No safety concerns were noted.
Enrolment: 57 participants (actual)
Lead sponsor: AlloVirIndustry (pharma, biotech, devices)
Study start: 26 Apr 2022 (actual)
Primary completion: 31 Jan 2024 (actual)
Study completion: 31 Jan 2024 (actual)
First posted: 5 Jan 2022 (actual)
Results: Posted 8 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study with option for blinded crossover to assess the safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in pediatric and adult recipients of HCT with AdV infections receiving SoC.

Arm	Type	Receives
Posoleucel + SoC	Experimental	Drug: PosoleucelPosoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria
Placebo + SoC	Placebo comparator	Drug: PlaceboPlacebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

Undergone allogeneic cell transplantation ≥21 days prior to dosing
Meet one of the below criteria:

Key exclusion criteria (6 listed)

Grade 3 or higher acute GVHD
Ongoing therapy with high-dose systemic corticosteroids
Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
Pregnant or lactating female unwilling to discontinue nursing prior to randomization
History of severe prior reactions to blood product transfusions

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PosoleucelAdministered as 2-4 milliliter infusion, visually identical to placebo	Drug	Posoleucel + SoC
PlaceboAdministered as 2-4 milliliter infusion, visually identical to Posoleucel	Drug	Placebo + SoC

Primary outcome

Number of Participants With Undetectable Adenovirus Infection
Time frame: Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)
Viral load of adenovirus was measured at the central laboratory using quantitative polymerase chain reaction (qPCR) from blood and stool samples at each study visit and on Day 29 from a nasopharyngeal swab. There was a 14-day window for participants who crossed over from posoleucel to placebo; and for participants who crossed over from placebo to posoleucel, the pre-dose cross-over Day 1 viral load was used. Participants missing the primary endpoint but having undetectable viremia before Day 29 and after Day 43 were imputed as successes. Undetectable adenovirus viremia was less than the lower limit of quantification (LLOQ).
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 34 weeks
A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included acute or chronic graft versus host disease, cytokine release syndrome, infusion-related reactions, and graft failure or rejection. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.

5 secondary outcomes

Number of Participants With Overall Disease Progression
Time frame: From Day 29 up to Week 10
Area Under the Curve (AUC) Adenovirus Viral Load
Time frame: Pre-dose and Day 29
Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29
Time frame: Day 29
Time to Undetectable Adenovirus Viremia (Less Than LLOQ)
Time frame: Pre-dose to 34 weeks
Number of Participants With Adenovirus Disease Recurrence
Time frame: 34 weeks

Results and safety

Results posted to the registry on 8 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Posoleucel, Then Placebo	30	10
Placebo, Then Posoleucel	27	13

Primary outcome: Number of Participants With Undetectable Adenovirus Infection

Time frame: Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion). Count of participants. Unit: Participants

Measure	Posoleucel, Then Placebo n = 25	Placebo, Then Posoleucel n = 21
Value	11	9

Posoleucel, Then Placebo vs Placebo, Then Posoleucel: Odds Ratio (OR): 0.98 (95% CI 0.26 to 3.69)

Population analysed: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of posoleucel or placebo. Only participants in the mITT population who completed through Day 29 or discontinued early were included.

Primary outcome: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

Time frame: Up to 34 weeks. Count of participants. Unit: Participants

Measure	Posoleucel (Primary Study Period) n = 28	Placebo (Primary Study Period) n = 23	Posoleucel (Cross-over Period) n = 5	Placebo (Cross-over Period) n = 4
Any TEAE	27	23	5	3
Any TEAE related to study treatment	7	9	1	1
Any AESI	6	9	1	2
Any SAE	16	16	3	1
Any SAE related to study treatment	1	1	1	1
Any TEAE leading to study treatment discontinuation	2	1	0	2
Any TEAE leading to study discontinuation	1	2	0	1
Any TEAE leading to death	2	1	0	1

Population analysed: The safety population included all participants who received any amount of posoleucel or placebo and had at least one post-treatment safety assessment.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 34 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Posoleucel (Primary Study Period)	16 of 28 (57.1%)	27 of 28 (96.4%)	2 of 28
Placebo (Primary Study Period)	16 of 23 (69.6%)	23 of 23 (100%)	1 of 23
Posoleucel (Cross-over Period)	3 of 5 (60%)	5 of 5 (100%)	0 of 5
Placebo (Cross-over Period)	1 of 4 (25%)	3 of 4 (75%)	1 of 4

Limitations and caveats (from the sponsor): The study was discontinued following a pre-planned DSMB futility analysis concluding that the study was unlikely to meet its primary endpoint, no safety concerns were identified.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38597860Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.
Individual participant dataSharing planned: No

Related trials for Adenovirus Infection

RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingObservational study
Viral Infections in Healthy and Immunocompromised Hosts
Anogenital Herpes, COVID-19
RecruitingPhase 2
Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection
Adenovirus, Primary Immune Deficiency Disorder
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

47 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Posoleucel in people with Adenovirus Infection, run by AlloVir at 47 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, Italy, United Kingdom, Spain, Sweden and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Undetectable Adenovirus Infection (time frame: Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05179057, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.