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Trial record 1 of 1 for:    V114-022
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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 : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Pneumococcal Infections Biological: V114 Biological: Prevnar 13™ Biological: PNEUMOVAX™23 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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)
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : November 10, 2021
Estimated Study Completion Date : November 10, 2021

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Arm Intervention/treatment
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.
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: 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

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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) >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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565900


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03565900     History of Changes
Other Study ID Numbers: V114-022
2018-000066-11 ( EudraCT Number )
V114-022 ( Other Identifier: Merck Protocol Number )
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Heptavalent Pneumococcal Conjugate Vaccine
Aluminum phosphate
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents