A STUDY OF A RSV VACCINE WHEN GIVEN TOGETHER WITH TDAP IN HEALTHY NONPREGNANT WOMEN AGED BETWEEN 18 TO 49 YEARS

Respiratory Tract Infection Clinical Trial

Official title:

A PHASE 2b, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE WHEN ADMINISTERED CONCOMITANTLY WITH TETANUS, DIPHTHERIA, AND ACELLULAR PERTUSSIS VACCINE (TDAP) IN HEALTHY NONPREGNANT WOMEN 18 THROUGH 49 YEARS OF AGE

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04071158
• Other study ID #: C3671004
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2019
• Est. completion date: December 11, 2019

Study information

• Verified date: January 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase 2b study will evaluate safety, tolerability, and immunogenicity of an RSV vaccine when given together with Tdap in approximately 710 healthy nonpregnant women 18 through 49 years of age. This study will evaluate non-inferiority of RSV vaccine when given with Tdap and vice-versa.

Description:

This Phase 2b study will evaluate safety, tolerability, and immunogenicity of an RSV vaccine when given together with Tdap in approximately 710 healthy nonpregnant women 18 through 49 years of age. The participants will be equally split into 5 treatment groups: One of a possible two dose levels of RSV vaccine (the higher dose level will be formulated with an aluminum hydroxide adjuvant) with either the Tdap or Placebo, or a Tdap and placebo combination. This study will evaluate non-inferiority of the Tdap when co-administered with RSV vaccine candidate and vice-versa by measuring participants' immune response through appropriate antibody and component levels 1 month after vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 713
• Est. completion date: December 11, 2019
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Healthy women =18 and =49 years of age who are of childbearing potential or not of childbearing potential. (Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.)
• Willing and able to comply with all scheduled visits, treatment plan, lifestyle considerations, and other study procedures.
• Expected to be available for the duration of the study and can be contacted by telephone during study participation.
• Body mass index (BMI) of <40 kg/m2 at the time of the consent.
• Capable of giving signed informed consent as which includes compliance with the requirements and restrictions listed within.

Exclusion Criteria:

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the vaccines being administered in the study.
• History of latex allergy.
• Immunocompromised participants with known or suspected immunodeficiency, as determined by history, laboratory tests, and/or physical examination.
• Any contraindication to Tdap (including encephalopathies).
• History of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin dependent diabetes mellitus (type 1).
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Previous vaccination with any licensed or investigational RSV vaccine, or planned receipt of nonstudy RSV vaccine throughout the study.
• Treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before investigational product administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
• Receipt of blood/plasma products or immunoglobulin within 60 days before investigational product administration or planned receipt throughout the study.
• Current alcohol abuse, marijuana abuse, or illicit drug use.
• Vaccination within 5 years with DTaP or tetanus and diphtheria toxoids adsorbed (Td) vaccine before investigational product administration.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
• Current febrile illness (oral temperature =38.0C [=100.4F]) or other acute illness within 48 hours before investigational product administration.
• Receipt of any inactivated vaccine within 14 days and any live vaccine within 28 days before or anticipated receipt of any vaccine within the 14 days after investigational product administration.
• Receipt of short-term (<14 days) systemic corticosteroids. Investigational product administration should be delayed until systemic corticosteroid use has been discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids do not require temporary delay of investigational product administration.

Related Conditions & MeSH terms

• Respiratory Tract Infection
• Respiratory Tract Infections

Intervention

Biological:
• RSV Vaccine
RSV vaccine
• Tdap
Tetanus, Diphtheria, and Acellular Pertussis Vaccine
• Placebo
Normal saline solution for injection (0.9% sodium chloride injection)

Locations

Country	Name	City	State
United States	Benchmark Research	Austin	Texas
United States	Meridian Clinical Research, LLC	Dakota Dunes	South Dakota
United States	Ventavia Research Group	Fort Worth	Texas
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Texas Center for Drug Development	Houston	Texas
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Meridian Clinical Research	Omaha	Nebraska
United States	Sundance Clinical Research	Saint Louis	Missouri
United States	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	J. Lewis Research, Inc / Jordan River Family Medicine	South Jordan	Utah
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Martin Diagnostic Clinic	Tomball	Texas
United States	Omega Medical Research	Warwick	Rhode Island
United States	Alliance for multispecialty research	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Achieving Anti-TTd Antibody Concentrations of >= 0.1 IU/mL Before Vaccination	Percentage of participants achieving Anti-TTd antibody concentrations of >= 0.1 IU/mL 1 month before vaccination were reported. The LLOQ values for Anti-TTd = 0.05 IU/mL. Assay results below the LLOQ were set to 0.5*LLOQ. Data for this outcome measure was not planned to be collected and analyzed for RSV 120 mcg with placebo arm and RSV 240 mcg with aluminum hydroxide/placebo arm.	Before vaccination on Day 1
Other	Percentage of Participants Achieving Anti- DTd Antibody Concentrations of >= 0.1 IU/mL Before Vaccination	Percentage of participants achieving Anti-DTd antibody concentrations of >= 0.1 IU/mL before vaccination were reported. The LLOQ values for Anti-DTd= 0.037 IU/mL. Assay results below the LLOQ were set to 0.5*LLOQ. Data for this outcome measure was not planned to be collected and analyzed for RSV 120 mcg with placebo arm and RSV 240 mcg with aluminum hydroxide/placebo arm.	Before vaccination on Day 1
Other	Geometric Mean Titer (GMT) of Respiratory Syncytial Virus Subgroup A (RSV A) Neutralizing Antibodies Before Vaccination	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol.	Before vaccination on Day 1
Other	Geometric Mean Titer (GMT) of Respiratory Syncytial Virus Subgroup B (RSV B) Neutralizing Antibodies Before Vaccination	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol.	Before vaccination on Day 1
Primary	Percentage of Participants Achieving Anti-Tetanus Toxoid (TTd) Antibody Concentrations of Greater Than or Equal to (>=) 0.1 International Units Per Milliliter (IU/mL) at 1 Month After Vaccination	Percentage of participants achieving Anti-TTd antibody concentrations of >= 0.1 IU/mL at 1 month after vaccination were reported. The lower limit of quantitation (LLOQ) values for Anti-TTd was 0.05 IU/mL. Assay results below the LLOQ were set to 0.5*LLOQ. Data for this outcome measure was planned to be collected and analyzed only for combined population of participants reported under two RSV vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) along with placebo/Tdap arm and not planned to be collected and analyzed for two RSV vaccine arms: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo), as pre-specified in protocol.	1 month after vaccination
Primary	Percentage of Participants Achieving Anti-Diphtheria Toxoid (DTd) Antibody Concentrations of >= 0.1 IU/mL at 1 Month After Vaccination	Percentage of participants achieving Anti-DTd antibody concentrations of >= 0.1 IU/mL at 1 month after vaccination were reported. The LLOQ values for Anti- DTd= 0.037 IU/mL. Assay results below the LLOQ were set to 0.5*LLOQ. Data for this outcome measure was planned to be collected and analyzed only for combined population of participants reported under two RSV vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) along with placebo/Tdap arm and not planned to be collected and analyzed for two RSV vaccine arms: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo), as pre-specified in protocol.	1 month after vaccination
Primary	Geometric Mean Concentration (GMC) and Geometric Mean Ratio (GMR) of Anti-Pertussis Antibodies 1 Month After Vaccination	GMCs of anti-pertussis components: anti pertussis (anti-PT) toxin, anti filamentous hemagglutinin (FHA) and anti- pertactin (PRN) was measured and reported in descriptive section. LLOQ values for each component was: Anti-PT=0.9 endotoxin units per milliliter (EU/mL), Anti-FHA=2.9 EU/mL, and Anti-PRN=3.0 EU/mL. Assay results below LLOQ were set to 0.5*LLOQ. Descriptive data for this outcome measure was planned to be collected and analyzed only for combined population of participants reported under two RSV vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) along with placebo/Tdap arm and not planned to be collected and analyzed for two RSV vaccine arms: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo), as pre-specified in protocol. GMRs were reported in statistical analysis section and calculated by dividing GMC of RSV vaccine with aluminum hydroxide with Tdap arm by GMC of placebo/Tdap arm.	1 month after vaccination
Primary	Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Respiratory Syncytial Virus Subgroup A (RSV A) Neutralizing Antibodies 1 Month After Vaccination Using 2.0 Fold Margin	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Descriptive data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol. GMRs were reported in statistical analysis section and calculated by dividing GMT of RSV vaccine with aluminum hydroxide with Tdap arm by GMT of RSV vaccine with aluminum hydroxide with placebo arm.	1 month after vaccination
Primary	Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Respiratory Syncytial Virus Subgroup B (RSV B) Neutralizing Antibodies 1 Month After Vaccination Using 2.0 Fold Margin	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Descriptive data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol. GMRs were reported in statistical analysis section and calculated by dividing GMT of RSV vaccine with aluminum hydroxide with Tdap arm by GMT of RSV vaccine with aluminum hydroxide with placebo arm.	1 month after vaccination
Primary	Percentage of Participants With Prespecified Local Reactions Within 7 Days After Vaccination	Local reactions included pain at injection site, redness and swelling recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm and severe: >10.0 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity and severe: prevented daily activity.	Within 7 days after vaccination
Primary	Percentage of Participants With Prespecified Systemic Reactions Within 7 Days After Vaccination	Systemic reactions included fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever was categorized as: >=38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.	Within 7 days after vaccination
Primary	Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Within 1 month after vaccination (up to 35 days)
Primary	Percentage of Participants With Medically Attended Adverse Events (MAE) and Serious Adverse Events (SAE)	An medically attended adverse events (MAE) was defined as a non-serious AE that results in an evaluation at a medical facility. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Within 1 month after vaccination (up to 35 days)
Secondary	Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Respiratory Syncytial Virus Subgroup A (RSV A) Neutralizing Antibodies 1 Month After Vaccination Using 1.5 Fold Margin	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Descriptive data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol. GMRs were reported in statistical analysis section and calculated by dividing GMT of RSV vaccine with aluminum hydroxide with Tdap arm by GMT of RSV vaccine with aluminum hydroxide with placebo arm.	1 month after vaccination
Secondary	Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Respiratory Syncytial Virus Subgroup B (RSV B) Neutralizing Antibodies 1 Month After Vaccination Using 1.5 Fold Margin	Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. Descriptive data for this outcome measure was planned to be collected and analyzed for combined population of participants reported under two RSV and Tdap vaccine arms: (RSV vaccine 120 mcg with Tdap and RSV vaccine 240 mcg with aluminum hydroxide/Tdap) and two RSV and placebo arm: (RSV vaccine 120 mcg with placebo and RSV vaccine 240 mcg with aluminum hydroxide with placebo) and not planned to be collected and analyzed for Placebo/Tdap arm, as pre-specified in protocol. GMRs were reported in statistical analysis section and calculated by dividing GMT of RSV vaccine with aluminum hydroxide with Tdap arm by GMT of RSV vaccine with aluminum hydroxide with placebo arm.	1 month after vaccination

External Links

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