IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 in Healthy Infants, Toddlers and Adults

NCT03092791 | Terminated Phase 1 Results DMC

• 2 other identifiers: IPV-102U1111-1191-6847
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 4

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).

Conditions

Poliomyelitis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (12)

• 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

  Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.

  Within 7 days of the First Dose given on Day 1

• 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

  Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.

  Within 7 days of the Second Dose given on Day 29

• 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

  Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.

  Within 7 Days of the Third Dose given on Day 57

• 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

  Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.

  Within 7 days of the First Dose given on Day 1

• 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

  Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.

  Within 7 days of the Second Dose given on Day 29

• 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

  Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.

  Within 7 Days of the Third Dose given on Day 57

• 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

  A systemic adverse event (AE) of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.

  Within 7 days of the First Dose given on Day 1

• 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

  A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.

  Within 7 days of the Second Dose given on Day 29

• 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

  A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.

  Within 7 days of the Third Dose given on Day 57

• 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

  An AE is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. Non-serious unsolicited AEs indicates any and all AEs (other than serious adverse events \[SAEs\]) that occurred other than those that are solicited.

  Within 28 days of primary vaccinations given on Days 1, 29 and 57 (Up to Day 85)

• Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV Study Arms in Infant Dose Ranging Cohort

  An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.

  Day 1 up to Day 547

• Percentage of Participants With Seroconversion

  Seroconversion is defined as i) initially seronegative infants (titer \<8 at Day 1) having a titer ≥8 at Day 85, or ii) initially seropositive infants (titer ≥8 at Day 1) with a 4-fold rise in antibody titers over the expected level of maternal antibodies at Day 85, calculated using a decline from the Day 1 titer with a half-life of 28 days.

  Day 85

Secondary Outcomes (22)

• 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

  Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)

• 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

  Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)

• 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

  Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57)

• 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

  Within 28 Days of primary vaccinations (Up to 85 days)

• Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV or IPV Study Arms in Infant Dose Ranging Cohort

  Day 1 up to Day 547

Study Arms (8)

Adult Lead-in Cohort: sIPV High Dose

EXPERIMENTAL

Sabin-based inactivated poliomyelitis vaccine (sIPV) containing 3, 100, and 100 D-Ag units (DU) of poliovirus types 1, 2, and 3, intramuscular injection on Day 1.

Biological: Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV)

Adult Lead-in Cohort: Placebo

PLACEBO COMPARATOR

Placebo, intramuscular injection on Day 1.

Biological: sIPV Placebo

Toddler Lead-in Cohort: sIPV High Dose

EXPERIMENTAL

sIPV containing 3, 100, and 100 DU of poliovirus types 1, 2, and 3, intramuscular injection on Day 1.

Biological: Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV)

Toddler Lead-in Cohort: Reference IPV

ACTIVE COMPARATOR

Reference IPV, intramuscular injection on Day 1.

Biological: Reference IPV

Infant Dose Ranging Cohort: sIPV Low Dose

EXPERIMENTAL

sIPV containing 0.75, 25, 25 DU of poliovirus types 1, 2, and 3, intramuscular injection on Days 1, 29, 57 and 365.

Biological: Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV)

Infant Dose Ranging Cohort: sIPV Medium Dose

EXPERIMENTAL

sIPV containing 1.5, 50, 50 DU of poliovirus types 1, 2, and 3, intramuscular injection on Days 1, 29 57 and 365.

Biological: Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV)

Infant Dose Ranging Cohort: sIPV High Dose

EXPERIMENTAL

sIPV containing 3, 100, 100 DU of poliovirus types 1, 2, and 3, intramuscular injection on Days 1, 29 57 and 365.

Biological: Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV)

Infant Dose Ranging Cohort: Reference IPV

ACTIVE COMPARATOR

Reference IPV, intramuscular injection on Days 1, 29 57 and 365.

Biological: Reference IPV

Interventions

Sabin-Based Inactivated Poliomyelitis Vaccine (sIPV) BIOLOGICAL

sIPV intramuscular injection

Adult Lead-in Cohort: sIPV High Dose; Infant Dose Ranging Cohort: sIPV High Dose; Infant Dose Ranging Cohort: sIPV Low Dose; Infant Dose Ranging Cohort: sIPV Medium Dose; Toddler Lead-in Cohort: sIPV High Dose

Reference IPV BIOLOGICAL

Reference IPV intramuscular injection

Infant Dose Ranging Cohort: Reference IPV; Toddler Lead-in Cohort: Reference IPV

sIPV Placebo BIOLOGICAL

sIPV placebo-matching intramuscular injection

Adult Lead-in Cohort: Placebo

Eligibility Criteria

• Age: 6 Weeks - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adult Lead-in Cohort
• 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.
• Completed primary immunization against poliomyelitis according to local recommendations.
• Toddler Lead-in Cohort
• 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.
• 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.
• \. Infants must have been born full term (37-42 weeks of gestation).

You may not qualify if:

• Adult Lead-in Cohort
• \. 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
• Last polio vaccination (either inactivated or oral) received within 5 months prior to first trial visit.
• 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
• Infants with low birth weight according to local standards.
• Prior vaccination with polio vaccines (either inactivated or oral).
• 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.
• All Cohorts
• Any significant chronic infection.
• 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.
• Known or suspected impairment/alteration of immune function, including:
• 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).
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (4)

CEVAXIN - David

Chiriquí, Panama

Location

CEVAXIN - 24 de Diciembre

Panama City, Panama

Location

CEVAXIN - Chorrera

Panama City, Panama

Location

CEVAXIN Plaza Carolina - Ciudad de Panama

Panama City, Panama

Location

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Senior Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

877-825-3327

Study Officials

• Senior Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: March 28, 2017
• Study Start: June 7, 2017
• Primary Completion: April 3, 2018
• Study Completion: October 18, 2018
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share

Locations

PA (4)