A Study to Assess the Safety and Efficacy of ALVR105 (Viralym-M) Compared to Placebo for the Prevention of AdV, BKV, CMV, EBV, HHV-6, and JCV Infection and/or Disease, in High-Risk Patients following bone marrow transplant
- Conditions
- Adenovirus (AdV), BK virus (BKV), John Cunningham virus (JCV), human herpesvirus 6 (HHV- 6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) infections and/or disease in patients at high risk for these viruses following allogeneic hematopoietic cell transplantMedDRA version: 21.1Level: PTClassification code 10060931Term: Adenovirus infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 20.1Level: PTClassification code 10055181Term: BK virus infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 22.0Level: PTClassification code 10020431Term: Human herpesvirus 6 infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 21.1Level: PTClassification code 10015108Term: Epstein-Barr virus infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 20.1Level: PTClassification code 10011831Term: Cytomegalovirus infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 21.1Level: PTClassification code 10023163Term: JC virus infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2021-005105-27-ES
- Lead Sponsor
- AlloVir, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 337
Age
1. Be =1 year of age at the day of screening visit.
Type of Participant and Disease Characteristics
2. Has no known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV
3. Be within 15 and 42 days of receiving a first allogeneic HCT at the time of randomization and have demonstrated clinical engraftment
4. High-risk: Patients meeting one or more of the following criteria at the time of randomization:
o Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B or -DR
o Haploidentical donor
o Unrelated donor
o Use of umbilical cord blood as stem cell source
o Ex vivo graft manipulation resulting in T cell depletion
o Received antithymocyte globulin (ATG) or alemtuzumab (Campath-1H)
Sex
5. Male and/or female
5. Male and/or female
a. Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of study intervention:
• Refrain from donating sperm PLUS, either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception /barrier as detailed below
• Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
b. Female participants:
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4.1 of the protocol
OR
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4.1 of the protocol
OR
• Is a WOCBP and using a highly effective method of contraception as described in Section 10.4.2 of the protocol during the study intervention period and for at least 90 days after the last dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative serum pregnancy test within 14 days
before the first dose of study intervention, see Section 8.4.7 of the protocol.
• Additional requirements for pregnancy testing during and after study intervention are located in Section 8.4.7 of the protocol.
Informed Consent and Cell Line Match
6. Willing and able to provide written informed consent as described in Section 10.1.3 of the protocol to participate in the study, or a parent or legal guardian is willing and able to provide written informed consent and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB) and local regulations.
7. Has an HLA type matching with at least 1 suitably matched and available ALVR105 VST line for infusion.
Are the trial subjects under 18? yes
Number of subjects for this age range: 67
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subject
Medical Conditions
1. Has a history of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
2. Evidence of active Grade >2 acute GVHD (for additional information on acute GVHD grading and severity, see Appendix 5 [Section 10.5 of the protocol]).
3. Presence of non-minor uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, fungemia, disseminated, and/or organ-specific infection not well controlled by present therapies)
4. Presence of any progressive, uncontrolled viral infections (ie, evidence of viremia, dissemination, and/or organ-specific infection not well controlled by present therapies).
5. Known history or current (suspected) diagnosis of CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies, see Appendix 6 [Section 10.6 of the protocol]).
6. Evidence of encephalopathy at screening visit
7. Relapse of primary malignancy other than minimal residual disease.
Prior/Concomitant Therapy
8. Donor lymphocyte infusion performed within 21 days prior to randomization
9. Received within 7 days prior to randomization any of the following:
ganciclovir, valganciclovir, foscarnet, acyclovir (at doses >3200 mg PO per day or >25 mg/kg IV per day), valacyclovir (at doses >3000 mg PO per day), famciclovir (at doses >1500 mg PO per day)
10. Participant has used any investigational antiviral agent, including brincidofovir, within 7 days prior to randomization or is actively receiving any investigational agent at randomization.
11. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day) within 24 hours prior to dosing
12. Prior therapy with ATG, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days prior to dosing
13. Receipt of mechanical ventilation of any type, within 1 month prior to treatment (unless related to airway control)
14. Undergoing dialysis at any time during the screening period
Prior/Concurrent Clinical Study Experience
15. Received a previous allogeneic HCT (Note: Receipt of a previous autologous HCT is acceptable)
Diagnostic Assessments
16. Aspartate aminotransferase or alanine aminotransferase serum levels >5 × the upper limit of normal (ULN) or direct bilirubin serum levels >3× the ULN.
Other Exclusions
17. Pregnant, breastfeeding, or planning to become pregnant during the study.
18. Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or would be put at undue risk as judged by the Investigator, such that it is not in the best interest of the patient to participate in this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method