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Prevnar

Phase 3

Pneumococcal Infections | Monoclonal antibody | Other |Merck & Company, Inc.|Last Updated: Jan 17, 2023

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment1,450
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03620162A Study to Evaluate the Interchangeability of V114 and Prevnar 13™ in Healthy Infants (V114-027/PNEU-DIRECTION)PHASE3 COMPLETED 900Oct 18, 2018Dec 14, 2020Jan 17, 202334 United States, Puerto Rico +2
NCT02225587Evaluation of the Safety and Immunogenicity of Sequential Administration of Prevnar 13™ and Pneumovax™ 23 in Healthy Participants 50 Years of Age and Older (V110-029)PHASE3 COMPLETED 400Aug 28, 2014Jul 6, 2015Nov 2, 2021 -
NCT01215175Safety and Tolerability Study for the Pneumococcal Conjugate Vaccine V114 Versus Prevnar™ (V114-001)PHASE1 COMPLETED 150Sep 25, 2009Jan 5, 2011Mar 18, 2019 -
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Study Endpoints
Primary Endpoints
Percentage of Participants With a Solicited Injection-site Adverse Event (AE)
Up to ~14 days after each vaccination

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. Per protocol, the percentage of participants with solicited injection-site AEs was assessed for up to \~14 days after each vaccination. The solicited injection-site AEs assessed were erythema/redness, induration/hard lump, tenderness/pain and swelling.

Percentage of Participants With a Solicited Systemic AE
Up to ~14 days after each vaccination

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. Per protocol, the percentage of participants with solicited systemic AEs was assessed for up to \~14 days after each vaccination. The solicited systemic AEs assessed were appetite lost/decreased appetite, irritability, drowsiness/somnolence and hives or welts/urticaria.

Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE)
Up to ~6 months after Vaccination 4 (up to ~19 months)

An SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgement. Relatedness of an SAE to the study vaccine was determined by the investigator. Per protocol, the percentage of participants with vaccine-related SAEs was assessed through 6 months following Vaccination 4.

Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4
30 Days after Vaccination 4 (Months 11-14)

The GMC of anti-PnP serotype-specific IgG for 13 shared serotypes contained in V114 and Prevnar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) was assessed using a pneumococcal electrochemiluminescence (PnECL) assay. Per protocol, 13 IgG serotypes in Groups 2, 3, 4 (experimental arms) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4 as a pre-specified primary outcome analysis; 13 IgG serotypes in Group 5 (experimental arm) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4, as a separate protocol-specified secondary outcome analysis and reported later in the record.

Percentage of Participants With an Adverse Event (AE)
Up to 14 days after any vaccination (Up to 28 weeks)

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Percentage of Participants With an Injection-site Adverse Event
Up to 14 days after any vaccination (Up to 28 weeks)

An injection site adverse event (AE) includes the following AEs at the injection site: redness, swelling, and pain/tenderness.

Percentage of Participants With a Systemic Adverse Event
Up to 14 days after any vaccination (Up to 28 weeks)

Systemic adverse events (AEs) include, but are not restricted to the following AE terms: muscle pain, joint pain, headache, and tiredness.

Percentage of Participants With a Serious Adverse Event (SAE)
Up to 30 weeks

A serious adverse event (SAE) is any adverse event occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; or is associated with an overdose.

Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) or Vaccine-related Death
Up to 30 weeks

A serious adverse event (SAE) is any adverse event occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; or is associated with an overdose. The investigator determined whether the SAE or death was related to vaccine treatment.

Percentage of Participants Who Discontinued Vaccination Due to an Adverse Event
Up to 26 weeks

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Geometric Mean Titers to Pneumococcal Serotypes 22F and 33F at Week 12
Week 12

Vaccine-induced functional antibodies to serotypes 22F and 33F, which are unique to PNEUMOVAX™ 23, were measured by the multiplex opsonophagocytic activity 4 (MOPA-4) assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.

Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, at Week 12
Week 12

Vaccine-induced functional antibodies to serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, which are contained in both Prevnar 13™ and PNEUMOVAX™ 23, were measured by the MOPA-4 assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.

Adult: Percentage of Participants With Any Adverse Event
Up to Day 14 after vaccination

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Toddler: Percentage of Participants With Any Adverse Event
Up to Day 14 after vaccination

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Adult: Percentage of Participants With Any Serious Adverse Event
Up to Day 14 after vaccination

A serious adverse event (SAE) is an AE that results in death, 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.

Toddler: Percentage of Participants With Any Serious Adverse Event
Up to Day 14 after vaccination

A serious adverse event (SAE) is an AE that results in death, 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.

Adult: Percentage of Participants With Any Vaccine-related Adverse Event
Up to Day 14 after vaccination

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Relatedness of the AE to study vaccine was determined by the investigator.

Toddler: Percentage of Participants With Any Vaccine-related Adverse Event
Up to Day 14 after vaccination

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Relatedness of the AE to study vaccine was determined by the investigator.

Secondary Endpoints
Group 5 Versus Group 1 + Group 2: Percentage of Participants With Anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3
30 Days after Vaccination 3 (Month 5)
Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3
30 Days after Vaccination 3 (Month 5)
GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3
30 Days after Vaccination 3 (Month 5)
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposePREVENTION
Treatment Arms
ArmTypeDescription
Group 1: Prevnar 13™-Prevnar 13™-Prevnar 13™-Prevnar 13™ACTIVE_COMPARATORParticipants will receive a single 0.5 mL intramuscular (IM) injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants will concomitantly receive other licensed background pediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.
Group 2: Prevnar 13™-Prevnar 13™-Prevnar 13™-V114EXPERIMENTALParticipants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and a single 0.5 mL IM injection of V114 on Months 10-13 (Vaccination 4). Participants will concomitantly receive other licensed background pediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.
Group 3: Prevnar 13™-Prevnar 13™-V114-V114EXPERIMENTALParticipants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2) and a single 0.5 mL IM injection of V114 on Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants will concomitantly receive other licensed background pediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.
Group 4: Prevnar 13™-V114-V114-V114EXPERIMENTALParticipants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of V114 on Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants will concomitantly receive other licensed background pediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.
Group 5: V114-V114-V114-V114EXPERIMENTALParticipants will receive a single 0.5 mL IM injection of V114 on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants will concomitantly receive other licensed background pediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.
Group 1: Prevnar 13™ → Pneumovax™ 23 → PlaceboEXPERIMENTALPrevnar 13™ 0.5 mL intramuscular injection on Day 1, Pneumovax™ 23 0.5 mL intramuscular injection at Week 8, and Placebo 0.5 mL intramuscular injection at Week 26. Injections are to be administered in alternating limbs, if possible.
Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23PLACEBO_COMPARATORPrevnar 13™ 0.5 mL intramuscular injection on Day 1, Placebo 0.5 mL intramuscular injection at Week 8, and Pneumovax™ 23 0.5 mL intramuscular injection at Week 26. Injections are to be administered in alternating limbs, if possible.
Prevnar™ - Adult CohortACTIVE_COMPARATORHealthy adult participants received a single 0.5 mL intramuscular injection of Prevnar™ on Day 1.
V114 Adjuvanted -Toddler CohortEXPERIMENTALHealthy toddler (12-15 months of age) participants who had completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of aluminum adjuvanted V114 on Day 1.
V114 Nonadjuvanted-Toddler CohortEXPERIMENTALHealthy toddlers (12-15 months of age) participants who completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of non-adjuvanted V114 on Day 1.
Prevnar™- Toddler CohortACTIVE_COMPARATORHealthy toddlers (12-15 months of age) participants who had previously completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of Prevnar™ on Day 1.
V114 Adjuvanted -Adult CohortEXPERIMENTALHealthy adult participants received a single 0.5 mL intramuscular injection of aluminum adjuvanted V114 on Day 1.
Interventions
NameTypeDescription
Prevnar 13™BIOLOGICALPrevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.
V114BIOLOGICALV114 contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose given via IM injection.
RotaTeq™BIOLOGICALRotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.
Pentacel™BIOLOGICALPentacel™ Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine, given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
RECOMBIVAX HB™BIOLOGICALRECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
HIBERIX™BIOLOGICALHIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
M-M-R™ IIBIOLOGICALM-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.
VARIVAX™BIOLOGICALVARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.
Pneumovax™ 23BIOLOGICALPneumococcal vaccine containing serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. Injections are to be administered into the deltoid muscle of the upper arm.
PlaceboBIOLOGICALInjections are to be administered into the deltoid muscle of the upper arm.
Prevnar™BIOLOGICAL13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), serotype 6B (4.4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.
V114, Aluminum AdjuvantedBIOLOGICAL15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.0 mcg each), serotype 6B (4.0 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.
V114, Aluminum NonadjuvantedBIOLOGICAL15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.0 mcg each), serotype 6B (4.0 mcg) in each 0.5 mL dose.
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Eligibility Criteria
Age Range42 Days — 90 Days
SexALL
Healthy VolunteersYes
Study Sites34

Inclusion Criteria: * Is Healthy, based on clinical judgment of the investigator * Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent...

Countries:United StatesPuerto RicoThailandTurkey (Türkiye)
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