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

NCT03565900 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0222018-000066-11
• Study Type: interventional
• Target: 277
• Locations: 10 countries
• Sites: 52

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 \[GVHD\]).

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)

• 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.

  Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)

• 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.

  Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)

• 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.

  Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)

• 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.

  Up to 9 months

• 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.

  Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)

Secondary Outcomes (13)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

V114

EXPERIMENTAL

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.

Biological: V114; Biological: PNEUMOVAX™23

Prevnar 13™

ACTIVE COMPARATOR

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.

Biological: Prevnar 13™; Biological: PNEUMOVAX™23

Interventions

V114 BIOLOGICAL

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.

Also known as: VAXNEUVANCE™, Pneumococcal 15-Valent Conjugate Vaccine

V114

Prevnar 13™ BIOLOGICAL

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

Prevnar 13™

PNEUMOVAX™23 BIOLOGICAL

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

Prevnar 13™; V114

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (52)

Stanford Health Care ( Site 0005)

Palo Alto, California, 94305, United States

Location

Children's Hospital Colorado ( Site 0166)

Aurora, Colorado, 80045, United States

Location

University of Florida ( Site 0011)

Gainesville, Florida, 32610, United States

Location

University of Chicago ( Site 0016)

Chicago, Illinois, 60637, United States

Location

Indiana Blood and Marrow Transplantation ( Site 0001)

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center ( Site 0007)

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins - University ( Site 0023)

Baltimore, Maryland, 21287, United States

Location

Children's Mercy Hospital ( Site 0167)

Kansas City, Missouri, 64108, United States

Location

Montefiore Einstein Center ( Site 0164)

The Bronx, New York, 10467, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0010)

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic Foundation ( Site 0168)

Cleveland, Ohio, 44106, United States

Location

Oregon Health & Science University ( Site 0018)

Portland, Oregon, 97239, United States

Location

Baylor College of Medicine - Texas Children's Hospital ( Site 0165)

Houston, Texas, 77030, United States

Location

St. Vincent's Hospital ( Site 0041)

Sydney, New South Wales, 2010, Australia

Location

The Children s Hospital at Westmead ( Site 0191)

Westmead, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital ( Site 0040)

Adelaide, South Australia, 5000, Australia

Location

Austin Health-Austin Hospital ( Site 0038)

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital ( Site 0037)

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital ( Site 0039)

Parkville, Victoria, 3050, Australia

Location

Cliniques Universitaires Saint-Luc ( Site 0122)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

Location

UZ Leuven ( Site 0119)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

AZ Sint Jan Brugge-Oostende ( Site 0118)

Bruges, West-Vlaanderen, 8000, Belgium

Location

AZ Delta ( Site 0120)

Roeselare, West-Vlaanderen, 8800, Belgium

Location

Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)

Liège, 4000, Belgium

Location

Hospital Sao Rafael ( Site 0049)

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Santa Casa de Misericordia de Belo Horizonte ( Site 0050)

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)

Curitiba, Paraná, 80510-130, Brazil

Location

Nova Scotia Health Authority QEII-HSC ( Site 0033)

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre ( Site 0032)

Hamilton, Ontario, L8V 1C3, Canada

Location

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)

Montreal, Quebec, H1T 2M4, Canada

Location

Hospital Pablo Tobon Uribe ( Site 0077)

Medellín, Antioquia, 050034, Colombia

Location

Fundacion Valle del Lili ( Site 0073)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Centro Medico Imbanaco de Cali S.A ( Site 0075)

Cali, Valle del Cauca Department, 760042, Colombia

Location

CHU de Nice ( Site 0084)

Nice, Alpes-Maritimes, 06002, France

Location

Hopital Jean Minjoz Besancon ( Site 0085)

Besançon, Doubs, 25030, France

Location

CHU de Grenoble Hopital Nord ( Site 0083)

La Tronche, Isere, 38700, France

Location

CHRU de Lille - Hopital Claude Huriez ( Site 0090)

Lille, Nord, 59037, France

Location

CHU Henri Mondor ( Site 0081)

Créteil, Val-de-Marne, 94000, France

Location

Hopital Saint-Antoine ( Site 0089)

Paris, 75012, France

Location

Universitaetsklinikum Koeln ( Site 0105)

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Universitaetsklinikum Duesseldorf ( Site 0107)

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitaetsmedizin Mainz ( Site 0106)

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)

Monterrey, Nuevo León, 64460, Mexico

Location

Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)

Monterrey, Nuevo León, 64460, Mexico

Location

Instituto Nacional de Pediatria ( Site 0062)

Mexico City, 04530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez ( Site 0061)

Mexico City, 06720, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)

Mexico City, 14080, Mexico

Location

Hospital Espanol ( Site 0059)

México, 11520, Mexico

Location

Instituto Nacional de Cancerologia. ( Site 0060)

México, 14080, Mexico

Location

Karolinska Universitetssjukhuset ( Site 0143)

Stockholm, Stockholms Lan [se-01], 141 86, Sweden

Location

Akademiska Sjukhuset ( Site 0144)

Uppsala, Uppsala Lan [se-03], 751 85, Sweden

Location

Sahlgrenska Universitetssjukhuset ( Site 0145)

Gothenburg, Vastra Gotalands Lan [se-14], 413 45, Sweden

Location

Related Publications (1)

• 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 Oct 13;77(8):1102-1110. doi: 10.1093/cid/ciad349.

  PMID: 37338158 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: June 21, 2018
• Study Start: September 12, 2018
• Primary Completion: November 4, 2021
• Study Completion: November 4, 2021
• Last Updated: July 28, 2023
• Results First Posted: October 20, 2022

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

BE (5); FR (6); BR (3); CA (3); DE (3); ME (7); SE (3); AU (6); US (13); CO (3)