Back to resultsA Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
Primary Purpose
Pneumococcal Infections
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
V114
Prevnar 13™
PNEUMOVAX™23
Sponsored by
About this trial
This is an interventional prevention trial for Pneumococcal Infections
Eligibility Criteria
Inclusion Criteria:
- Received a human leukocyte antigen (HLA) compatible donor including haploidentical and mismatched (related or unrelated) first allogeneic HSCT (i.e., bone marrow or peripheral blood stem cell) 90 to 180 days prior to randomization.
- Received the allogeneic HSCT for acute lymphoblastic leukemia (ALL) in first or second remission, acute myeloid leukemia (AML) in first or second remission, chronic myeloid leukemia (CML) in first chronic or accelerated phase, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myelofibrosis and myeloproliferative diseases, and non-malignant disease such as aplastic anemia or sickle cell disease in participants ≥18 years of age and any non-malignant disease for participants 3 to <18 years of age.
- Life expectancy >12 months after allogeneic HSCT, according to investigator judgement.
- Clinically stable engraftment according to investigator judgment.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a) not a woman of childbearing potential (WOCBP) OR b) a WOCBP who agrees to use acceptable contraceptive methods during the treatment period and for at least 6 weeks after the last dose of study intervention.
Exclusion Criteria:
- Receipt of a previous allogeneic HSCT.
- Received allogeneic HSCT with ex-vivo graft manipulation, in vivo T cell depletion with alemtuzumab, or haploidentical allogeneic HSCT with high dose anti-thymocyte globulin.
- Received allogeneic HSCT for multiple myeloma or, for participants ≥18 years of age only, for any nonmalignant diseases except sickle cell disease and aplastic anemia.
- Persistent or relapsed primary disease after allogeneic HSCT.
- History of severe GVHD (Grade 3 or 4 GVHD) after allogeneic HSCT.
- Planned organ transplantation after allogeneic HSCT.
- History of culture-positive pneumococcal disease occurring after allogeneic HSCT.
- Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine.
- History of acquired immunodeficiency such as documented HIV infection, or anatomic asplenia.
- Coagulation disorder contraindicating intramuscular vaccinations.
- Severe hepatic impairment (defined as Child-Pugh Class C) at Screening.
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) >6 × upper limit of normal (ULN) or serum total bilirubin >2.5 × ULN at Screening.
- A WOCBP who has a positive urine or serum pregnancy test before the 1st vaccination.
- Received chimeric antigen receptor T-cell (CAR-T) therapy or checkpoint inhibitor directed therapy (i.e., anti-Programmed Cell Death (PD)-1) after allogeneic HSCT.
- Received or planned to receive anti-Cluster of Differentiation (CD) 20 B-cell targeted therapy (e.g., rituximab) after allogeneic HSCT.
- Non-study pneumococcal vaccine administered after allogeneic HSCT, or is expected to receive non-study pneumococcal vaccine during participation in the study.
- Is currently participating or has participated in an interventional clinical study with an investigational compound/agent or device within 2 weeks of participating in this current study, or plans to receive any investigational compound/agent or device (in addition to existing therapy) within 2 weeks of any vaccination, that in the opinion of the investigator would interfere with the evaluation of the study objectives.
- Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence as assessed by the study investigator.
- Has history or current evidence of any condition, therapy, laboratory test result abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.
- Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study.
Sites / Locations
- Stanford Health Care ( Site 0005)
- Children's Hospital Colorado ( Site 0166)
- University of Florida ( Site 0011)
- University of Chicago ( Site 0016)
- Indiana Blood and Marrow Transplantation ( Site 0001)
- University of Kansas Medical Center ( Site 0007)
- Johns Hopkins - University ( Site 0023)
- Children's Mercy Hospital ( Site 0167)
- Montefiore Einstein Center ( Site 0164)
- Cincinnati Children's Hospital Medical Center ( Site 0010)
- Cleveland Clinic Foundation ( Site 0168)
- Oregon Health & Science University ( Site 0018)
- Baylor College of Medicine - Texas Children's Hospital ( Site 0165)
- St. Vincent's Hospital ( Site 0041)
- The Children s Hospital at Westmead ( Site 0191)
- Royal Adelaide Hospital ( Site 0040)
- Austin Health-Austin Hospital ( Site 0038)
- The Alfred Hospital ( Site 0037)
- Royal Melbourne Hospital ( Site 0039)
- Cliniques Universitaires Saint-Luc ( Site 0122)
- UZ Leuven ( Site 0119)
- AZ Sint Jan Brugge-Oostende ( Site 0118)
- AZ Delta ( Site 0120)
- Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)
- Hospital Sao Rafael ( Site 0049)
- Santa Casa de Misericordia de Belo Horizonte ( Site 0050)
- Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)
- Nova Scotia Health Authority QEII-HSC ( Site 0033)
- Juravinski Cancer Centre ( Site 0032)
- CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)
- Hospital Pablo Tobon Uribe ( Site 0077)
- Fundacion Valle del Lili ( Site 0073)
- Centro Medico Imbanaco de Cali S.A ( Site 0075)
- CHU de Nice ( Site 0084)
- Hopital Jean Minjoz Besancon ( Site 0085)
- CHU de Grenoble Hopital Nord ( Site 0083)
- CHRU de Lille - Hopital Claude Huriez ( Site 0090)
- CHU Henri Mondor ( Site 0081)
- Hopital Saint-Antoine ( Site 0089)
- Universitaetsklinikum Duesseldorf ( Site 0107)
- Universitaetsklinikum Koeln ( Site 0105)
- Universitaetsmedizin Mainz ( Site 0106)
- Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)
- Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)
- Instituto Nacional de Pediatria ( Site 0062)
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)
- Hospital Infantil de Mexico Federico Gomez ( Site 0061)
- Hospital Espanol ( Site 0059)
- Instituto Nacional de Cancerologia. ( Site 0060)
- Karolinska Universitetssjukhuset ( Site 0143)
- Akademiska Sjukhuset ( Site 0144)
- Sahlgrenska Universitetssjukhuset ( Site 0145)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
V114
Prevnar 13™
Arm Description
Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic graft-versus-host-disease (GVHD) during the first year after HSCT will receive V114 instead of PNEUMOVAX™23 as their fourth dose.
Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic GVHD during the first year after HSCT will receive Prevnar 13™ instead of PNEUMOVAX™23 as their fourth dose.
Outcomes
Primary Outcome Measures
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, induration, pain, and swelling.
Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were arthralgia, fatigue, headache, and myalgia.
Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were arthralgia, fatigue, headache, myalgia, and hives or welts.
Percentage of Participants With a Vaccine-related Serious Adverse Event Up to Month 12 After Allogeneic HSCT
A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 1 (with either V114 or Prevnar 13™) was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 up to 12 months post-HSCT, which could be up to 9 months post-vaccine dose 1.
Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
The GMC of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay.
Secondary Outcome Measures
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following single dose vaccination with PNEUMOVAX™23, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were induration, pain, swelling, and erythema.
Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs were arthralgia, fatigue, headache, and myalgia.
Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were fatigue, headache, myalgia, hives or welts, and arthralgia.
Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With PNEUMOVAX™23
A SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following a single dose vaccination with PNEUMOVAX™23 was reported.
Adult Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
This end point applies to adult participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Pediatric Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
This end point applies to pediatric participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination dose. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AE assessed were pain, erythema, swelling, and induration.
Adult Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
This end point applies to adult participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination dose. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs were arthralgia, fatigue, headache, and myalgia.
Pediatric Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
This end point applies to pediatric participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed myalgia, arthralgia, headache, fatigue, and hives or welts.
Participants With GVHD: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Dose 4 With V114 or Prevnar 13™
This end point applies to participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as vaccine dose 4. An SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 4 with V114 or Prevnar 13™ through completion of study was reported.
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
The GMT of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay.
Percentage of Participants With Geometric Mean Fold Rises (GMFR) ≥4 in Serotype-specific IgG at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
The GMFR of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay.
Percentage of Participants With GMFR ≥4 in Serotype-specific OPA at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
Activity for the 15 serotypes contained in V114 vaccine were determined using a Multiplex Opsonophagocytic Assay. The GMFR of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using multiplexed opsonophagocytic assay.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03565900
Brief Title
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
Official Title
A Phase 3, Randomized, Double-blind, Active Comparator-controlled, Multicenter Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Recipients of Allogeneic Hematopoietic Stem Cell Transplant (PNEU-STEM)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
September 12, 2018 (Actual)
Primary Completion Date
November 4, 2021 (Actual)
Study Completion Date
November 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to 1) evaluate the safety and tolerability, and immunogenicity of blinded V114 and Prevnar 13™ within each vaccination group, and 2) evaluate the safety and tolerability, and immunogenicity of PNEUMOVAX™23 (administered as open label, 12 months after allogeneic hematopoietic stem cell transplant [allo-HSCT] in participants who do not develop chronic graft-versus-host disease [GVHD]).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumococcal Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
277 (Actual)
8. Arms, Groups, and Interventions
Arm Title
V114
Arm Type
Experimental
Arm Description
Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic graft-versus-host-disease (GVHD) during the first year after HSCT will receive V114 instead of PNEUMOVAX™23 as their fourth dose.
Arm Title
Prevnar 13™
Arm Type
Active Comparator
Arm Description
Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic GVHD during the first year after HSCT will receive Prevnar 13™ instead of PNEUMOVAX™23 as their fourth dose.
Intervention Type
Biological
Intervention Name(s)
V114
Other Intervention Name(s)
VAXNEUVANCE™, Pneumococcal 15-Valent Conjugate Vaccine
Intervention Description
15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose.
Intervention Type
Biological
Intervention Name(s)
Prevnar 13™
Intervention Description
13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg), and aluminum phosphate adjuvant (125 mcg aluminum) in each 0.5 ml dose
Intervention Type
Biological
Intervention Name(s)
PNEUMOVAX™23
Intervention Description
23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose
Primary Outcome Measure Information:
Title
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
Description
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Time Frame
Up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
Title
Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, induration, pain, and swelling.
Time Frame
Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
Title
Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were arthralgia, fatigue, headache, and myalgia.
Time Frame
Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
Title
Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the first 3 doses of V114 or Prevnar 13™, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were arthralgia, fatigue, headache, myalgia, and hives or welts.
Time Frame
Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
Title
Percentage of Participants With a Vaccine-related Serious Adverse Event Up to Month 12 After Allogeneic HSCT
Description
A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 1 (with either V114 or Prevnar 13™) was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 up to 12 months post-HSCT, which could be up to 9 months post-vaccine dose 1.
Time Frame
Up to 9 months
Title
Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
Description
The GMC of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay.
Time Frame
Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
Secondary Outcome Measure Information:
Title
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Time Frame
Up to 5 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following single dose vaccination with PNEUMOVAX™23, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were induration, pain, swelling, and erythema.
Time Frame
Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs were arthralgia, fatigue, headache, and myalgia.
Time Frame
Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following a single dose vaccination with PNEUMOVAX™23, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were fatigue, headache, myalgia, hives or welts, and arthralgia.
Time Frame
Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With PNEUMOVAX™23
Description
A SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following a single dose vaccination with PNEUMOVAX™23 was reported.
Time Frame
Up to 1 month after PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 10 months after Day 1)
Title
Adult Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
Description
This end point applies to adult participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of adult participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, pain, and swelling.
Time Frame
Up to 5 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Pediatric Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
Description
This end point applies to pediatric participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination dose. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of pediatric participants with solicited injection-site AEs was assessed. The solicited injection-site AE assessed were pain, erythema, swelling, and induration.
Time Frame
Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Adult Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
Description
This end point applies to adult participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination dose. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of adult participants with solicited systemic AEs was assessed. The solicited systemic AEs were arthralgia, fatigue, headache, and myalgia.
Time Frame
Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Pediatric Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
Description
This end point applies to pediatric participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as the fourth vaccination. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following dose 4 with V114 or Prevnar 13™, the percentage of pediatric participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed myalgia, arthralgia, headache, fatigue, and hives or welts.
Time Frame
Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
Title
Participants With GVHD: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Dose 4 With V114 or Prevnar 13™
Description
This end point applies to participants who developed GVHD within 12 months of HSCT and received V114 or Prevnar 13™ as vaccine dose 4. An SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 4 with V114 or Prevnar 13™ through completion of study was reported.
Time Frame
Up to 6 months after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 15 months after Day 1)
Title
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
Description
The GMT of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay.
Time Frame
Up to Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
Title
Percentage of Participants With Geometric Mean Fold Rises (GMFR) ≥4 in Serotype-specific IgG at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
Description
The GMFR of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay.
Time Frame
Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
Title
Percentage of Participants With GMFR ≥4 in Serotype-specific OPA at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
Description
Activity for the 15 serotypes contained in V114 vaccine were determined using a Multiplex Opsonophagocytic Assay. The GMFR of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using multiplexed opsonophagocytic assay.
Time Frame
Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Received a human leukocyte antigen (HLA) compatible donor including haploidentical and mismatched (related or unrelated) first allogeneic HSCT (i.e., bone marrow or peripheral blood stem cell) 90 to 180 days prior to randomization.
Received the allogeneic HSCT for acute lymphoblastic leukemia (ALL) in first or second remission, acute myeloid leukemia (AML) in first or second remission, chronic myeloid leukemia (CML) in first chronic or accelerated phase, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myelofibrosis and myeloproliferative diseases, and non-malignant disease such as aplastic anemia or sickle cell disease in participants ≥18 years of age and any non-malignant disease for participants 3 to <18 years of age.
Life expectancy >12 months after allogeneic HSCT, according to investigator judgement.
Clinically stable engraftment according to investigator judgment.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a) not a woman of childbearing potential (WOCBP) OR b) a WOCBP who agrees to use acceptable contraceptive methods during the treatment period and for at least 6 weeks after the last dose of study intervention.
Exclusion Criteria:
Receipt of a previous allogeneic HSCT.
Received allogeneic HSCT with ex-vivo graft manipulation, in vivo T cell depletion with alemtuzumab, or haploidentical allogeneic HSCT with high dose anti-thymocyte globulin.
Received allogeneic HSCT for multiple myeloma or, for participants ≥18 years of age only, for any nonmalignant diseases except sickle cell disease and aplastic anemia.
Persistent or relapsed primary disease after allogeneic HSCT.
History of severe GVHD (Grade 3 or 4 GVHD) after allogeneic HSCT.
Planned organ transplantation after allogeneic HSCT.
History of culture-positive pneumococcal disease occurring after allogeneic HSCT.
Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine.
History of acquired immunodeficiency such as documented HIV infection, or anatomic asplenia.
Coagulation disorder contraindicating intramuscular vaccinations.
Severe hepatic impairment (defined as Child-Pugh Class C) at Screening.
Serum aspartate transaminase (AST) or alanine transaminase (ALT) >6 × upper limit of normal (ULN) or serum total bilirubin >2.5 × ULN at Screening.
A WOCBP who has a positive urine or serum pregnancy test before the 1st vaccination.
Received chimeric antigen receptor T-cell (CAR-T) therapy or checkpoint inhibitor directed therapy (i.e., anti-Programmed Cell Death (PD)-1) after allogeneic HSCT.
Received or planned to receive anti-Cluster of Differentiation (CD) 20 B-cell targeted therapy (e.g., rituximab) after allogeneic HSCT.
Non-study pneumococcal vaccine administered after allogeneic HSCT, or is expected to receive non-study pneumococcal vaccine during participation in the study.
Is currently participating or has participated in an interventional clinical study with an investigational compound/agent or device within 2 weeks of participating in this current study, or plans to receive any investigational compound/agent or device (in addition to existing therapy) within 2 weeks of any vaccination, that in the opinion of the investigator would interfere with the evaluation of the study objectives.
Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence as assessed by the study investigator.
Has history or current evidence of any condition, therapy, laboratory test result abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.
Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Health Care ( Site 0005)
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital Colorado ( Site 0166)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida ( Site 0011)
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Chicago ( Site 0016)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana Blood and Marrow Transplantation ( Site 0001)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
University of Kansas Medical Center ( Site 0007)
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins - University ( Site 0023)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Children's Mercy Hospital ( Site 0167)
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Montefiore Einstein Center ( Site 0164)
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center ( Site 0010)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Cleveland Clinic Foundation ( Site 0168)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Oregon Health & Science University ( Site 0018)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Baylor College of Medicine - Texas Children's Hospital ( Site 0165)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
St. Vincent's Hospital ( Site 0041)
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Children s Hospital at Westmead ( Site 0191)
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Adelaide Hospital ( Site 0040)
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Austin Health-Austin Hospital ( Site 0038)
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
The Alfred Hospital ( Site 0037)
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Royal Melbourne Hospital ( Site 0039)
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc ( Site 0122)
City
Brussels
State/Province
Bruxelles-Capitale, Region De
ZIP/Postal Code
1200
Country
Belgium
Facility Name
UZ Leuven ( Site 0119)
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
AZ Sint Jan Brugge-Oostende ( Site 0118)
City
Brugge
State/Province
West-Vlaanderen
ZIP/Postal Code
8000
Country
Belgium
Facility Name
AZ Delta ( Site 0120)
City
Roeselare
State/Province
West-Vlaanderen
ZIP/Postal Code
8800
Country
Belgium
Facility Name
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Hospital Sao Rafael ( Site 0049)
City
Salvador
State/Province
Bahia
ZIP/Postal Code
41253-190
Country
Brazil
Facility Name
Santa Casa de Misericordia de Belo Horizonte ( Site 0050)
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30150-221
Country
Brazil
Facility Name
Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)
City
Curitiba
State/Province
Paraná
ZIP/Postal Code
80510-130
Country
Brazil
Facility Name
Nova Scotia Health Authority QEII-HSC ( Site 0033)
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
Juravinski Cancer Centre ( Site 0032)
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Facility Name
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Hospital Pablo Tobon Uribe ( Site 0077)
City
Medellin
State/Province
Antioquia
ZIP/Postal Code
050034
Country
Colombia
Facility Name
Fundacion Valle del Lili ( Site 0073)
City
Cali
State/Province
Valle Del Cauca
ZIP/Postal Code
760032
Country
Colombia
Facility Name
Centro Medico Imbanaco de Cali S.A ( Site 0075)
City
Cali
State/Province
Valle Del Cauca
ZIP/Postal Code
760042
Country
Colombia
Facility Name
CHU de Nice ( Site 0084)
City
Nice
State/Province
Alpes-Maritimes
ZIP/Postal Code
06002
Country
France
Facility Name
Hopital Jean Minjoz Besancon ( Site 0085)
City
Besancon
State/Province
Doubs
ZIP/Postal Code
25030
Country
France
Facility Name
CHU de Grenoble Hopital Nord ( Site 0083)
City
La Tronche
State/Province
Isere
ZIP/Postal Code
38700
Country
France
Facility Name
CHRU de Lille - Hopital Claude Huriez ( Site 0090)
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Henri Mondor ( Site 0081)
City
Creteil
State/Province
Val-de-Marne
ZIP/Postal Code
94000
Country
France
Facility Name
Hopital Saint-Antoine ( Site 0089)
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Universitaetsklinikum Duesseldorf ( Site 0107)
City
Duesseldorf
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
40225
Country
Germany
Facility Name
Universitaetsklinikum Koeln ( Site 0105)
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50931
Country
Germany
Facility Name
Universitaetsmedizin Mainz ( Site 0106)
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Instituto Nacional de Pediatria ( Site 0062)
City
Ciudad de Mexico
ZIP/Postal Code
04530
Country
Mexico
Facility Name
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)
City
Ciudad de Mexico
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Hospital Infantil de Mexico Federico Gomez ( Site 0061)
City
Mexico City
ZIP/Postal Code
06720
Country
Mexico
Facility Name
Hospital Espanol ( Site 0059)
City
Mexico
ZIP/Postal Code
11520
Country
Mexico
Facility Name
Instituto Nacional de Cancerologia. ( Site 0060)
City
Mexico
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Karolinska Universitetssjukhuset ( Site 0143)
City
Stockholm
State/Province
Stockholms Lan [se-01]
ZIP/Postal Code
141 86
Country
Sweden
Facility Name
Akademiska Sjukhuset ( Site 0144)
City
Uppsala
State/Province
Uppsala Lan [se-03]
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Sahlgrenska Universitetssjukhuset ( Site 0145)
City
Goteborg
State/Province
Vastra Gotalands Lan [se-14]
ZIP/Postal Code
413 45
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
37338158
Citation
Wilck M, Cornely OA, Cordonnier C, Velez JD, Ljungman P, Maertens J, Selleslag D, Mullane KM, Nabhan S, Chen Q, Dagan R, Richmond P, Daus C, Geddie K, Tamms G, Sterling T, Patel SM, Shekar T, Musey L, Buchwald UK; V114-022 (PNEU-STEM) study group. A phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in allogeneic hematopoietic cell transplant recipients (PNEU-STEM). Clin Infect Dis. 2023 Jun 20:ciad349. doi: 10.1093/cid/ciad349. Online ahead of print.
Results Reference
result
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
We'll reach out to this number within 24 hrs