Clinical trial NCT03092791: IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 in Healthy Infants, Toddlers and Adults
Official title: A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated Poliomyelitis Vaccine From Sabin Strains in Healthy Infants, With a Safety and Tolerability Age-Step Down Lead-in in Healthy Adults Followed by Healthy Toddlers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Poliomyelitis
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-03-28
Enrollment: 340
Sex: ALL
Minimum age (years): 6
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to select the optimal antigen dosage of the three Sabin poliovirus strains (types 1, 2, and 3) entering the composition of the stand-alone trivalent Sabin-based inactivated poliomyelitis vaccine (sIPV) to take forward into advanced stage studies. The selection will be carried out comparing the three sIPV study arms based on the safety and tolerability profile after each dose of primary immunization and the immune response to poliovirus types 1, 2, and 3 for both Sabin and Salk strains, after the final dose of a three dose primary immunization series (Day 85).

Detailed description: The vaccine being tested in this study is called sIPV. sIPV is used to prevent poliomyelitis. This study will look at the safety, tolerability of sIPV in healthy adults, toddlers and infants as well as safety and immunogenicity in toddlers and infants. .

The study will enroll approximately 340 participants including 40 adults, 60 toddlers and 240 infants. Adult participants will be randomly assigned to one of the two treatment groups-which will remain undisclosed to study doctor and participants during the study (unless there is an urgent medical need):

* sIPV High Dose
* Placebo (saline control - 0.9% sodium chloride)

Toddler participants will be randomly assigned to one of the following treatment groups:

* sIPV High Dose
* Reference IPV

Infant participants will be randomly assigned to one of following treatment groups:

* sIPV Low Dose
* sIPV Medium Dose
* sIPV High Dose
* Reference IPV Adults and toddlers will receive intramuscular injection on Day 1. Infants will receive intramuscular injection on Days 1, 29, 57 and 365.

This is a multicentre trial. The overall time to participate in this study for adult is 8 days, for toddlers is 183 days and infants is 547 days.

Eligibility criteria: Inclusion Criteria:

Adult Lead-in Cohort

1. Individuals who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
2. Completed primary immunization against poliomyelitis according to local recommendations.

Toddler Lead-in Cohort

1. Toddlers in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
2. Completed primary immunization against poliomyelitis, preferably with IPV, according to local recommendations.

Infant Dose Ranging Cohort 1. Infants are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.

3. Infants must have been born full term (37-42 weeks of gestation).

Exclusion Criteria:

Adult Lead-in Cohort

1. Has body mass index (BMI) greater than or equal to 35 kg/m\^2 (= weight in kg \[height in meters \* height in meters\].

Toddler Lead-in Cohort

1. Last polio vaccination (either inactivated or oral) received within 5 months prior to first trial visit.
2. Household member/sibling who had received or is/are scheduled to receive Oral Poliomyelitis Vaccine (OPV) in the previous 3 months until 5 weeks post participant's inclusion in the study.
3. Prior vaccination with booster dose of diphtheria, tetanus, pertussis (acellular or whole cell), polio (either inactivated or oral), or Haemophilus influenzae type b (Hib) vaccines.

Infant Dose Ranging Cohort

1. Infants with low birth weight according to local standards.
2. Prior vaccination with polio vaccines (either inactivated or oral).
3. Household member/sibling that had received or is/are scheduled to receive OPV in the previous 3 months until 5 weeks after the third dose of the primary immunization series.
4. Prior vaccination with any diphtheria, tetanus, pertussis (acellular or whole cell), Haemophilus influenzae type b (Hib) vaccine or polio vaccine (OPV or IPV). Note, bacillus Calmette Guérin (BCG) at birth and prior vaccination with Hepatitis B vaccine given at least 4 weeks prior to first trial visit are not exclusion criteria.

All Cohorts

1. Any significant chronic infection.
2. Any clinically significant active infection (as assessed by the investigator) or temperature ≥38.0°C (\>100.4°F), within 3 days of intended trial vaccination.
3. Known or suspected impairment/alteration of immune function, including:

   1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone for ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1.
   3. Administration of immunoglobulins and/or any blood or blood products within the 3 months preceding the administration of the trial vaccine or planned administration during the trial
   4. Receipt of immunostimulants within 60 days prior to Day 1.
   5. Genetic immunodeficiency.
4. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

Primary outcomes:
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1
timeFrame: Within 7 days of the First Dose given on Day 1
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 29
timeFrame: Within 7 days of the Second Dose given on Day 29
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 57
timeFrame: Within 7 Days of the Third Dose given on Day 57
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1
timeFrame: Within 7 days of the First Dose given on Day 1
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 29
timeFrame: Within 7 days of the Second Dose given on Day 29
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 57
timeFrame: Within 7 Days of the Third Dose given on Day 57
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV on Day 1
timeFrame: Within 7 days of the First Dose given on Day 1
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV on Day 29
timeFrame: Within 7 days of the Second Dose given on Day 29
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV on Day 57
timeFrame: Within 7 days of the Third Dose given on Day 57
measure: Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort
timeFrame: Within 28 days of primary vaccinations given on Days 1, 29 and 57 (Up to Day 85)
measure: Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV Study Arms in Infant Dose Ranging Cohort
timeFrame: Day 1 up to Day 547
measure: Percentage of Participants With Seroconversion
timeFrame: Day 85
Secondary outcomes:
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV by Severity in Infant Dose Ranging Cohort
timeFrame: Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV by Severity in Infant Dose Ranging Cohort
timeFrame: Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV in Infant Dose Ranging Cohort
timeFrame: Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)
measure: Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV in Infant Dose Ranging Cohort
timeFrame: Within 28 Days of primary vaccinations (Up to 85 days)
measure: Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV or IPV Study Arms in Infant Dose Ranging Cohort
timeFrame: Day 1 up to Day 547
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort
timeFrame: Within 28 days of booster vaccination given on Day 365
measure: Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort
timeFrame: Within 7 days of booster vaccination given on Day 365
measure: Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort
timeFrame: Within 28 Days of booster vaccination given on Day 365
measure: Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in Toddler Lead-in Cohort
timeFrame: Day 1 up to Day 183
measure: Number of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort
timeFrame: Within 7 days of sIPV or placebo vaccination
measure: Number of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort
timeFrame: Within 7 days of sIPV or placebo vaccination
measure: Number of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort
timeFrame: Within 7 days of sIPV or placebo vaccination dose given on Day 1
measure: Number of Participants Experiencing Non-serious Unsolicited AEs Within the 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort
timeFrame: Within 7 days of sIPV or placebo vaccination
measure: Number of Participants Experiencing SAEs Throughout the Entire Trial Duration in Adult Lead-in Cohort
timeFrame: Day 1 up to Day 8
measure: Seropositivity/Seroprotection Rate (SPR) on Days 85, 365 and 393 in Infant Dose Ranging Cohort
timeFrame: Days 85, 365 and 393
measure: Geometric Mean Titers (GMT) on Days 85, 365 and 393 in Infant Dose Ranging Cohort
timeFrame: Days 85, 365 and 393
measure: Vaccine Response Rate (VRR) on Day 393 in Infant Dose Ranging Cohort
timeFrame: Day 393
Other outcomes:
Locations:
city: Chiriqui
country: Panama
facility: CEVAXIN - David
city: Ciudad de Panama
country: Panama
facility: CEVAXIN Plaza Carolina - Ciudad de Panama
city: Panama
country: Panama
facility: CEVAXIN - 24 de Diciembre
city: Panama
country: Panama
facility: CEVAXIN - Chorrera
Study officials:
affiliation: Takeda
name: Senior Medical Director Clinical Science
role: STUDY_DIRECTOR
References: