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Completed

NCT Number: NCT03950856

Lot-to-Lot Consistency of V114 in Healthy Adults (V114-020)

The primary objectives are to evaluate the safety and tolerability of V114 and to compare the serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) across 3 different lots of V114. The primary hypothesis is that all 3 lots of V114 are equivalent as measured by the serotype-specific OPA GMTs for 15 serotypes in V114 at 30 days postvaccination.

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Key information

Conditions

Pneumococcal Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Lung Diseases Pneumonia Pneumonia, Bacterial Pneumonia, Pneumococcal Respiratory Tract Diseases Respiratory Tract Infections Streptococcal Infections

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 6006), Blacktown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant has good health in the opinion of the investigator. Any underlying chronic condition must be documented to be in stable condition according to the investigator's judgment.
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Female participant is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to use agreed upon contraception during the treatment period and for at least 6 weeks after the last dose of study intervention.

Exclusion criteria

  • History of invasive pneumococcal disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1).
  • Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine.
  • Known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease.
  • Coagulation disorder contraindicating intramuscular vaccinations.
  • Recent febrile illness (defined as oral or tympanic temperature ≥100.4°F [≥38.0°C] or axillary or temporal temperature ≥99.4°F [≥37.4°C]) or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of study vaccine.
  • History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  • A WOCBP who has a positive urine or serum pregnancy test before the first vaccination at Visit 1 (Day 1).
  • Has received any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside of the protocol.
  • Has received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention at least 30 days before study entry.
  • Has received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination. (Note: Topical, ophthalmic, intra-articular or soft-tissue [e.g., bursa, tendon steroid injections], and inhaled/nebulized steroids are permitted).
  • Is receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease.
  • Has received any non-live vaccine within the 14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine within 30 days following receipt of any study vaccine. (Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of any study vaccine or at least 15 days after receipt of any study vaccine.)
  • Has received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days following receipt of any study vaccine. If this exclusion criterion is met, then Day 1 Visit may be rescheduled for a time when criterion is not met.
  • Has received a blood transfusion or blood products, including immunoglobulin, within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion.
  • Currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study.
  • In the opinion of the investigator, has a history of clinically relevant drug or alcohol use that would interfere with participation in protocol-specified activities.
  • History or current evidence of any condition, therapy, laboratory 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 (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Treatment and study plan

V114

Drug

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.

Prevnar 13™

Drug

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F in each 0.5. mL dose.

Primary outcomes

  1. Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With Separate V114 Lots

    Time frame: Up to Day 5

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consisted of redness/erythema, swelling, and tenderness/pain. The 95% confidence interval (CI) were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with solicited injection-site AEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.

  2. Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™

    Time frame: Up to Day 5

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consisted of redness/erythema, swelling, and tenderness/pain. Per the statistical analysis plan, within-group CIs were not calculated.

  3. Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With Separate V114 Lots

    Time frame: Up to Day 14

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs consisted of muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. The 95% CI were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with solicited systemic AEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.

  4. Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™

    Time frame: Up to Day 14

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs consisted of muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. Per the statistical analysis plan, within-group CIs were not calculated.

  5. Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With Separate V114 Lots

    Time frame: Up to Month 6

    A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. Relatedness of an SAE to the study vaccine is determined by the investigator. The 95% CI were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with SAEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.

  6. Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™

    Time frame: Up to Month 6

    A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. Relatedness of an SAE to the study vaccine is determined by the investigator. Per the statistical analysis plan, within-group CIs were not calculated.

  7. Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Following Vaccination With Separate V114 Lots

    Time frame: Day 30

    Opsonization of pneumococci for phagocytosis is an important mechanism by which antibodies to polysaccharides protect against disease in vivo. Sera from participants was used to measure geometric mean titer (GMT) of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, using the Multiplexed Opsonophagocytic Assay (MOPA). Per the statistical analysis plan, within-group CIs were not calculated. 95% CIs were calculated for the GMT ratios between pairs of V114 lots by a constrained longitudinal data analysis (cLDA) model; and the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.

Secondary outcomes

  1. Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) Following Vaccination With Separate V114 Lots

    Time frame: Day 30

    The geometric mean concentration (GMC) of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by multiplex electrochemiluminescence (ECL) using the pneumococcal electrochemiluminescence (PnECL) v2.0 assay. Per the statistical analysis plan, within-group CIs were not calculated; and the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.

  2. Geometric Mean Concentration of Serotype-specific IgG Following Vaccination: Combined Lots of V114 or Prevnar 13™

    Time frame: Day 30

    The GMC of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. Per the statistical analysis plan, within-group CIs were not calculated,

  3. Geometric Mean Fold Rise (GMFR) in Serotype-specific OPA Following Vaccination With Separate V114 Lots

    Time frame: Day 1 (Baseline) and Day 30

    Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, using the MOPA which reads the reciprocal of the highest dilution that gives ≥50% bacterial killing. The Geometric Mean Fold Rise (GMFR) is the geometric mean of the ratio Day 30/Day 1 OPA responses. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.

  4. GMFR in Serotype-specific IgG Following Vaccination With Separate V114 Lots

    Time frame: Day 1 (Baseline) and Day 30

    The geometric mean concentration (GMC) of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. The GMFR is the geometric mean of the ratio Day 30/Day 1 IgG concentration. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.

  5. Percentage of Participants With ≥4 Fold Change in Serotype-specific OPA Following Vaccination With Separate V114 Lots

    Time frame: Day 1 (Baseline) and Day 30

    Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, with the MOPA which reads the reciprocal of the highest dilution (1/dil) that gives ≥50% bacterial killing. Percentage of participants with a ≥ 4-fold change from Day 1 (baseline) to Day 30 (Day 30/Day 1) are presented. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.

  6. Percentage of Participants With ≥4 Fold Change in Serotype-specific IgG Following Vaccination With Separate V114 Lots

    Time frame: Day 1 (Baseline) and Day 30

    The geometric mean concentration of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. Percentage of participants with a ≥ 4-fold change from Day 1 (baseline) to Day 30 (Day 30/ Day 1) are presented. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled, Lot-to-Lot Consistency Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-TRUE)

Acronym: PNEU-TRUE

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
May 15, 2019
Registry last updated
Apr 12, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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