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

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ClinicalTrials.gov Identifier: NCT03565900
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE June 12, 2018
First Posted Date  ICMJE June 21, 2018
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE September 12, 2018
Estimated Primary Completion Date November 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
  • Adult Participants: Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: 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. Solicited injection-site AEs will be redness/erythema, swelling, and pain/tenderness.
  • Pediatric Participants: Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: Up to 14 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. Solicited injection-site AEs will be redness/erythema, swelling, pain/tenderness, and hard lump.
  • Adult Participants: Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.
  • Pediatric Participants: Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, tiredness/fatigue, and hives or welts.
  • Percentage of Participants with a Vaccine-related Serious Adverse Event [ Time Frame: Up to the time of PNEUMOVAX™23 vaccination (12 months after HSCT and up to 9 months after Day 1) ]
    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. Relatedness of an SAE to the study vaccine will be determined by the investigator.
  • Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™) ]
    Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay.
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
  • Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: Up to Day 5 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. Solicited injection-site AEs will be redness/erythema, swelling, and pain/tenderness.
  • Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: Up to Day 14 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.
  • Percentage of Participants with a Vaccine-related Serious Adverse Event [ Time Frame: Up to 9 months after the Day 1 vaccination (12 months after HSCT, before PNEUMOVAX™23 vaccination) ]
    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. Relatedness of an SAE to the study vaccine will be determined by the investigator.
  • Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccination with either V114 or Prevnar 13™) ]
    Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay.
Change History Complete list of historical versions of study NCT03565900 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
  • Adult Participants: Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: 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. Solicited injection-site AEs will be redness/erythema, swelling, and pain/tenderness.
  • Pediatric Participants: Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: Up to 5 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1) ]
    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. Solicited injection-site AEs will be redness/erythema, swelling, pain/tenderness, and hard lump
  • Adult Participants: Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.
  • Pediatric Participants: Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, tiredness/fatigue, and hives or welts.
  • Percentage of Participants with a Vaccine-related Serious Adverse Event [ Time Frame: Up to 1 month after PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 10 months after Day 1) ]
    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. Relatedness of an SAE to the study vaccine will be determined by the investigator.
  • Adult Participants with GVHD: Percentage of Participants with a Solicited Injection-site Adverse Event [ 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) ]
    This Outcome Measure applies to adult participants who develop GVHD within 12 months of HSCT and receive 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. Solicited injection-site AEs will be redness/erythema, swelling, and pain/tenderness.
  • Pediatric Participants with GVHD: Percentage of Participants with a Solicited Injection-site Adverse Event [ 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) ]
    This Outcome Measure applies to pediatric participants who develop GVHD within 12 months of HSCT and receive 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. Solicited injection-site AEs will be redness/erythema, swelling, pain/tenderness, and hard lump.
  • Adult Participants with GVHD: Percentage of Participants with a Solicited Systemic Adverse Event [ 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) ]
    This Outcome Measure applies to adult participants who develop GVHD within 12 months of HSCT and receive 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.
  • Pediatric Participants with GVHD: Percentage of Participants with a Solicited Systemic Adverse Event [ 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) ]
    This Outcome Measure applies to pediatric participants who develop GVHD within 12 months of HSCT and receive 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, tiredness/fatigue, and hives or welts.
  • Participants with GVHD: Percentage of Participants with a Vaccine-related Serious Adverse Event [ 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) ]
    This Outcome Measure applies to participants who develop GVHD within 12 months of HSCT and receive V114 or Prevnar 13™ as the fourth vaccination. 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. Relatedness of an SAE to the study vaccine will be determined by the investigator.
  • Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity [ 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 will be determined using a Multiplex Opsonophagocytic Assay.
  • Percentage of Participants with GMFR ≥4 in Serotype-specific IgG [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™) ]
    Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay.
  • Percentage of Participants with GMFR ≥4 in Serotype-specific OPA [ 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 will be determined using a Multiplex Opsonophagocytic Assay.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
  • Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: Up to Day 5 after the PNEUMOVAX™23 vaccination at 12 months after HSCT (approximately 6 to 9 months after Day 1 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. Solicited injection-site AEs will be redness/erythema, swelling, and pain/tenderness.
  • Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: Up to Day 14 after the PNEUMOVAX™23 vaccination at 12 months after HSCT (approximately 6 to 9 months after Day 1 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. Solicited systemic AEs will be muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.
  • Percentage of Participants with a Vaccine-related Serious Adverse Event [ Time Frame: From Month 12 to Month 13 after HSCT (predose and 1 month after PNEUMOVAX™23 vaccination) ]
    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. Relatedness of an SAE to the study vaccine will be determined by the investigator.
  • Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccination with either V114 or Prevnar 13™) ]
    Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay.
  • Percentage of Participants with GMFR ≥4 in Serotype-specific IgG [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccination with either V114 or Prevnar 13™) ]
    Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay.
  • Percentage of Participants with GMFR ≥4 in Serotype-specific OPA [ Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccination with either V114 or Prevnar 13™) ]
    Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
Official Title  ICMJE 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)
Brief Summary This study is designed 1) to describe the safety, tolerability, and immunogenicity of V114 and Prevnar 13™ in pneumococcal vaccine-naïve adult and pediatric recipients of allogeneic hematopoietic stem cell transplant (HSCT), and 2) to describe the safety and tolerability of PNEUMOVAX™23 when administered 12 months after HSCT.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Pneumococcal Infections
Intervention  ICMJE
  • Biological: V114
    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.
  • Biological: Prevnar 13™
    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
  • Biological: PNEUMOVAX™23
    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
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Biological: V114
    • Biological: PNEUMOVAX™23
  • Active Comparator: 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.
    Interventions:
    • Biological: Prevnar 13™
    • Biological: PNEUMOVAX™23
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 3, 2018)
300
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2018)
250
Estimated Study Completion Date  ICMJE November 10, 2021
Estimated Primary Completion Date November 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) >5 × 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Colombia,   France,   Germany,   Mexico,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03565900
Other Study ID Numbers  ICMJE V114-022
2018-000066-11 ( EudraCT Number )
V114-022 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP