DTaP-IPV-HB-PRP-T Combined Vaccine as a Primary Series and a Second Year of Life Booster in HIV-Exposed Infected and Uninfected Infants

NCT02817451 | Completed Phase 3

• 3 other identifiers: A3L44U1111-1161-26102018-004708-21
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess and confirm the adequate immunogenicity and safety profile of the Sanofi Pasteur's DTaP-Hep B-IPV-PRP-T fully liquid combined hexavalent vaccine administered in HIV-exposed uninfected infants and in HIV-exposed infected infants. The primary objectives of the study are:

• To evaluate the immunogenicity of the study vaccine 1 month after the 3-dose primary series in HIV-exposed infected and in HIV-exposed uninfected infants.
• To describe the persistence of all antibodies before receipt of the booster dose in HIV-exposed infected and in HIV-exposed uninfected infants.
• To evaluate the immunogenicity of the study vaccine 1 month after the booster dose in HIV-exposed infected and in HIV-exposed uninfected infants. The secondary objectives of the study are:
• To describe the safety profile after each and all doses of the study vaccine administered as a 3-dose infant primary series in HIV-exposed infected and in HIV-exposed uninfected infants.
• To describe the safety profile of the study vaccine administered as a booster in HIV-exposed infected and in HIV-exposed uninfected infants.

Conditions

Diphtheria; Tetanus; Pertussis; Hepatitis B; Polio; Human Immunodeficiency Virus Infection

Keywords

Diphtheria; Tetanus; Pertussis; Hepatitis B; DTaP IPV HB PRP-T Combined Vaccine; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (9)

• Number of Participants with Anti-Pertussis Toxoid (PT) and Anti-Filamentous Hemagglutinin (FHA) Antibody (Ab) Concentrations >= Lower Limit of Quantification (LLOQ) and >=4*LLOQ at Baseline

  Anti-PT and anti-FHA Ab concentrations are determined in terms of endotoxin units per millilitre (EU/mL).

  Day 0 (baseline)

• Geometric Means of Anti-Pertussis Toxoid and Anti-Filamentous Hemagglutinin Antibody Concentrations at Baseline

  Anti-PT and anti-FHA Ab levels are measured by electrochemiluminescence immunoassay (ECL) and anti-PT and anti-FHA Ab concentrations are determined in terms of EU/mL.

  Day 0 (baseline)

• Geometric Means of Antibody Titers/Concentrations After Primary Series Vaccination

  Anti-diphtheria, anti-tetanus, anti-PT and anti-FHA Ab levels are measured by ECL. Anti-poliovirus types 1, 2, and 3 Ab levels are measured by neutralisation assay. Anti-Hep B Ab levels are measured by VITROS ECi/ECiQ Immunodiagnostic system using chemiluminescence detection technology. Anti-polyribosylribitol phosphate (PRP) Ab levels are measured using a Farr-type radioimmunoassay (RIA). Ab concentrations are determined as: anti-diphtheria \>=0.01 international units (IU)/mL, \>=0.1 IU/mL, 1.0 IU/mL, anti-tetanus \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-PT and anti-FHA EU/mL, anti-PRP \>=0.15 microgram (mcg)/mL, \>=1.0 mcg/mL, anti-Poliovirus types 1, 2, and 3 Ab titers \>=8 (1/dilution \[dil\]), Anti-Hep B \>=10 milli (m) IU/mL, and \>=100 mIU/mL.

  Day 90 (1 month after third dose)

• Number of Participants With Seroprotection After Primary Series Vaccination

  Seroprotection is determined as: anti-diptheria Ab concentrations \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-tetanus Ab concentrations \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-PT and anti-FHA Ab concentrations EU/mL (\>=LLOQ and \>=4\*LLOQ), anti-PRP Ab concentrations \>=0.15 mcg/mL and \>=1.0 mcg/mL, anti-poliovirus 1, 2, and 3 Ab titers \>=8 (1/dil), anti-Hep B Ab concentrations \>=10 mIU/mL and \>=100 mIU/mL.

  Day 90 (1 month after third dose)

• Number of Participants with Vaccine Response or Seroconversion After Primary Series Vaccination

  Vaccine response is defined for anti-PT and anti-FHA as Ab post-Dose 3 concentrations \>=4\*LLOQ, if pre-Dose (Day 0) Ab concentration is \<4\*LLOQ or 1 month after third dose (Day 90) concentrations \>= pre-Dose Ab concentrations if pre-Dose (Day 0) concentrations \>=4\*LLOQ. Seroconversion for anti-PT and anti-FHA is defined as \>=4-fold Ab concentrations increase from pre-Dose (Day 0) to 1 month after third dose (Day 90).

  Day 0 (baseline), Day 90 (1 month after third dose)

• Geometric Means of Antibody Titers/Concentrations After Booster Vaccination

  Anti-diphtheria, anti-tetanus, anti-PT, and anti-FHA Ab levels are measured by ECL. Anti-poliovirus types 1, 2, and 3 Ab levels are measured by neutralisation assay. Anti-Hep B Ab levels are measured by VITROS ECi/ECiQ Immunodiagnostic system using chemiluminescence detection technology. Anti-PRP Ab levels are measured using a Farr-type RIA. Ab concentrations: anti-diphtheria \>=0.01 IU/mL, \>=0.1 IU/mL, \>=1.0 IU/mL, anti-tetanus \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-PT and anti-FHA EU/mL, anti-PRP \>=0.15 mcg/mL, \>=1.0 mcg/mL, anti-poliovirus 1, 2, and 3 Ab titers \>=8 (1/dil), anti-Hep B \>=10 mIU/mL, and \>=100 mIU/mL.

  Day 420 (1 month after booster vaccination)

• Number of Participants With Seroprotection After Booster Vaccination

  Seroprotection: anti-diphtheria Ab concentrations \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-tetanus Ab concentrations \>=0.01 IU/mL, \>=0.1 IU/mL, and \>=1.0 IU/mL, anti-PT and anti-FHA Ab concentrations EU/mL (\>=LLOQ and \>=4\*LLOQ), anti-PRP Ab concentrations \>=0.15 mcg/mL and \>=1.0 mcg/mL, anti-poliovirus 1, 2, and 3 Ab titers \>=8 (1/dil), and anti-Hep B Ab concentrations \>=10 mIU/mL and \>=100 mIU/mL.

  Day 420 (1 month after booster vaccination)

• Number of Participants With Vaccine Response or Seroconversion After Booster Vaccination

  Vaccine response is defined for anti-PT and anti-FHA as \>=4 fold Ab concentrations increase from pre-dose (Day 0) to 1 month after booster dose (Day 420), if pre-Dose (Day 0) Ab concentrations \<4\*LLOQ; or \>=2 fold Ab concentrations increase from pre- dose (Day 0) to 1 month after booster dose (Day 420), if pre-dose (Day 0) Ab concentrations \>=4\*LLOQ. Seroconversion is defined for anti-PT and anti-FHA as \>=4 fold Ab concentrations increase from pre-dose (Day 0) to 1 month after booster dose.

  Day 0 (baseline), Day 420 (1 month after booster vaccination)

• Number of Participants With Booster Response After Booster Vaccination

  Booster response is defined for anti-PT and anti-FHA as \>=4 fold Ab concentrations increase from pre-booster (Day 390) to 1 month after booster dose (Day 420), if pre-booster Ab concentrations \<4\*LLOQ; or \>=2 fold Ab concentrations increase from pre-booster (Day 390) to 1 month after booster dose (Day 390) if pre-Booster Ab concentrations \>=4\*LLOQ.

  Day 390 (pre-booster), Day 420 (1 month after booster dose)

Secondary Outcomes (7)

• Number of Participants With Immediate Unsolicited Adverse Events (AE) After Primary Series Vaccination

  Within 30 minutes after vaccination

• Number of Participants With Solicited Injections Site or Systemic Reactions After Primary Series Vaccination

  Within 7 days after vaccination

• Number of Participants With Unsolicited Adverse Events After Primary Series Vaccination

  Within 30 days after vaccination

• Number of Participants With Serious Adverse Events During the Study

  Day 0 to Day 420

• Number of Participants With Immediate Unsolicited Adverse Events After Booster Vaccination

  Within 30 minutes after booster vaccination

Study Arms (2)

Study Group A

EXPERIMENTAL

HIV exposed and infected infants

Biological: Hexaxim®: DTaP-IPV-HB-PRP-T Combined Vaccine

Study Group B

EXPERIMENTAL

HIV exposed and uninfected infants

Biological: Hexaxim®: DTaP-IPV-HB-PRP-T Combined Vaccine

Interventions

Hexaxim®: DTaP-IPV-HB-PRP-T Combined Vaccine BIOLOGICAL

0.5 mL, Intramuscular at 6, 10, and 14 weeks of age + a booster at age 15 to 18 months

Also known as: Hexaxim®

Study Group A

Eligibility Criteria

• Age: 5 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• (Screening Criteria for the participants mother)
• At least 18 years of age at the time of the Screening blood sample draw
• Self-reported or maternity-reported HIV infection in the mother
• Group A participants must be HIV infected, as documented through the results of a polymerase chain reaction (PCR) test, and following an anti-retroviral therapy according to the national recommendations; and Group B participants must be HIV exposed uninfected infants, as documented through the results of a PCR test.
• Born with a birth weight ≥ 2.0 kg
• Informed consent form signed by the parent(s)/legal guardian(s) and by one independent witness if the parent(s)/legal guardian(s) is illiterate
• Participants and parent(s)/legal guardian(s) are able to attend all scheduled visits and to comply with all trial procedures.

You may not qualify if:

• Group A participants diagnosed with a chronic condition, except HIV infection, or any experience of blood or blood-derived products received or experience of thrombocytopenia or bleeding disorder; and Group B participants diagnosed with chronic illness or any experience of blood or blood-derived products received or experience of thrombocytopenia or bleeding disorder.
• History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infections (confirmed either clinically, serologically or microbiologically)
• History of seizures or history of uncontrolled neurologic disorder or uncontrolled epilepsy until treatment for the condition has been established, the condition has stabilized and the benefit clearly outweighs the risk
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Unknown Facility

Soweto, South Africa

Location

MeSH Terms

Conditions

Diphtheria; Tetanus; Whooping Cough; Hepatitis B; Poliomyelitis; Acquired Immunodeficiency Syndrome

Interventions

DTaP-IPV-HB-PRP-T vaccine

Condition Hierarchy (Ancestors)

Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Clostridium Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: June 29, 2016
• Study Start: July 14, 2016
• Primary Completion: February 22, 2019
• Study Completion: February 22, 2019
• Last Updated: April 5, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

ZA (1)