A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)

Phase 3

Completed

Conditions: Pneumococcal Infections

Interventions: Biological: Prevnar 13™
Biological: V114
Biological: PNEUMOVAX™23

Registration Number: NCT03565900

Lead Sponsor: Merck Sharp & Dohme LLC

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 \[GVHD\]).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 277

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prevnar 13™	Prevnar 13™	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.
V114	V114	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.
V114	PNEUMOVAX™23	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.
Prevnar 13™	PNEUMOVAX™23	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.

Primary Outcome Measures

Name	Time	Method
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™	Up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations (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™	Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (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™	Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (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™	Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (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	Up to 9 months	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)	Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)	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

Name	Time	Method
Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23	Up to 5 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)	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.
Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With PNEUMOVAX™23	Up to 1 month after PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 10 months after Day 1)	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.
Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23	Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)	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	Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)	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 With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™	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)	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™	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)	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™	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)	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™	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)	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.
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)	Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)	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)	Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)	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.
Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23	Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)	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.
Adult Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™	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)	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.
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)	Up to Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)	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.

Trial Locations

Locations (52): St. Vincent's Hospital ( Site 0041)
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Sydney, New South Wales, Australia
Hospital Sao Rafael ( Site 0049)
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Salvador, Bahia, Brazil
Baylor College of Medicine - Texas Children's Hospital ( Site 0165)
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Houston, Texas, United States
Cincinnati Children's Hospital Medical Center ( Site 0010)
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Cincinnati, Ohio, United States
Montefiore Einstein Center ( Site 0164)
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Bronx, New York, United States
Children's Hospital Colorado ( Site 0166)
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Aurora, Colorado, United States
Santa Casa de Misericordia de Belo Horizonte ( Site 0050)
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Belo Horizonte, Minas Gerais, Brazil
University of Kansas Medical Center ( Site 0007)
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Kansas City, Kansas, United States
Royal Adelaide Hospital ( Site 0040)
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Adelaide, South Australia, Australia
AZ Delta ( Site 0120)
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Roeselare, West-Vlaanderen, Belgium
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)
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Liège, Belgium
Austin Health-Austin Hospital ( Site 0038)
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Heidelberg, Victoria, Australia
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)
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Montreal, Quebec, Canada
The Alfred Hospital ( Site 0037)
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Melbourne, Victoria, Australia
Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)
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Curitiba, Paraná, Brazil
Fundacion Valle del Lili ( Site 0073)
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Cali, Valle Del Cauca, Colombia
CHU de Nice ( Site 0084)
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Nice, Alpes-Maritimes, France
Universitaetsklinikum Koeln ( Site 0105)
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Koeln, Nordrhein-Westfalen, Germany
University of Florida ( Site 0011)
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Gainesville, Florida, United States
Hopital Saint-Antoine ( Site 0089)
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Paris, France
Hospital Pablo Tobon Uribe ( Site 0077)
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Medellin, Antioquia, Colombia
CHRU de Lille - Hopital Claude Huriez ( Site 0090)
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Lille, Nord, France
Johns Hopkins - University ( Site 0023)
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Baltimore, Maryland, United States
Hospital Espanol ( Site 0059)
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Mexico, Mexico
Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)
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Monterrey, Nuevo Leon, Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)
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Ciudad de Mexico, Mexico
Oregon Health & Science University ( Site 0018)
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Portland, Oregon, United States
Stanford Health Care ( Site 0005)
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Palo Alto, California, United States
Indiana Blood and Marrow Transplantation ( Site 0001)
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Indianapolis, Indiana, United States
University of Chicago ( Site 0016)
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Chicago, Illinois, United States
Children's Mercy Hospital ( Site 0167)
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Kansas City, Missouri, United States
Cleveland Clinic Foundation ( Site 0168)
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Cleveland, Ohio, United States
The Children s Hospital at Westmead ( Site 0191)
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Westmead, New South Wales, Australia
Royal Melbourne Hospital ( Site 0039)
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Parkville, Victoria, Australia
Cliniques Universitaires Saint-Luc ( Site 0122)
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Brussels, Bruxelles-Capitale, Region De, Belgium
AZ Sint Jan Brugge-Oostende ( Site 0118)
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Brugge, West-Vlaanderen, Belgium
UZ Leuven ( Site 0119)
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Leuven, Vlaams-Brabant, Belgium
Nova Scotia Health Authority QEII-HSC ( Site 0033)
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Halifax, Nova Scotia, Canada
Juravinski Cancer Centre ( Site 0032)
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Hamilton, Ontario, Canada
CHU de Grenoble Hopital Nord ( Site 0083)
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La Tronche, Isere, France
Centro Medico Imbanaco de Cali S.A ( Site 0075)
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Cali, Valle Del Cauca, Colombia
Hopital Jean Minjoz Besancon ( Site 0085)
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Besancon, Doubs, France
Universitaetsmedizin Mainz ( Site 0106)
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Mainz, Rheinland-Pfalz, Germany
CHU Henri Mondor ( Site 0081)
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Creteil, Val-de-Marne, France
Universitaetsklinikum Duesseldorf ( Site 0107)
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Duesseldorf, Nordrhein-Westfalen, Germany
Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)
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Monterrey, Nuevo Leon, Mexico
Instituto Nacional de Pediatria ( Site 0062)
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Ciudad de Mexico, Mexico
Karolinska Universitetssjukhuset ( Site 0143)
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Stockholm, Stockholms Lan [se-01], Sweden
Hospital Infantil de Mexico Federico Gomez ( Site 0061)
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Mexico City, Mexico
Instituto Nacional de Cancerologia. ( Site 0060)
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Mexico, Mexico
Akademiska Sjukhuset ( Site 0144)
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Uppsala, Uppsala Lan [se-03], Sweden
Sahlgrenska Universitetssjukhuset ( Site 0145)
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Goteborg, Vastra Gotalands Lan [se-14], Sweden