Phase I Clinical Trial of Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine

NCT06184542 | Recruiting Phase 1 DMC

• 1 other identifier: 20200610
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a randomized, blinded, active-controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of the Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine (DTacP) in subjects (aged 2 months to 6 years). Primary safety endpoints are the occurrence of solicited adverse events within 30 minutes after each dose, the occurrence of solicited adverse events within 7 days after each dose, the occurrence of unsolicited adverse events within 30 days after each dose, and the occurrence of adverse events 30 days after immunization. The secondary safety endpoint is the occurrence of serious adverse events (SAEs) within 12 months after immunization. Secondary immunogenicity endpoints are the geometric mean concentration (GMC), geometric mean fold increase (GMFI), seropositive rates, seroconversion rates, or 4-fold increase rates of anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN antibodies 30 days after immunization. The exploratory endpoints are the GMC, GMFI, seropositive rates, seroconversion rates, or 4-fold increase rates of anti-DT, anti-PT, and anti-FHA neutralizing antibodies 30 days after immunization in all groups, the GMC and seropositive rates of anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN antibodies 12 months after primary immunization in the infant group, the seropositive rates and geometric mean tie (GMT) of anti- type I, type II, type III poliovirus neutralizing antibodies 30 days after immunization in all groups, the seropositive rates and geometric mean tie (GMT) of anti- type I, type II, type III poliovirus neutralizing antibodies 12 months after primary immunization in the infant group.

Conditions

Diphtheria; Tetanus; Pertussis

Outcome Measures

Primary Outcomes (13)

• Safety index-incidence of adverse events

  Incidence of adverse events after the first dose vaccination (Applicable for Infants)

  0-30 minutes after the first dose vaccination

• Safety index-incidence of adverse events

  Incidence of adverse events after the second dose vaccination (Applicable for Infants)

  0-30 minutes after the second dose vaccination

• Safety index-incidence of adverse events

  Incidence of adverse events after the third dose vaccination (Applicable for Infants)

  0-30 minutes after the third dose vaccination

• Safety index-incidence of adverse events

  Incidence of adverse events after the booster dose (Applicable for Toddlers and Children)

  0-30 minutes after the booster dose

• Safety index-incidence of solicited adverse events

  Incidence of solicited adverse events after the first dose vaccination (Applicable for Infants)

  Day 0 to 7 after the first dose vaccination

• Safety index-incidence of solicited adverse events

  Incidence of solicited adverse events after the second dose vaccination (Applicable for Infants)

  Day 0 to 7 after the second dose vaccination

• Safety index-incidence of solicited adverse events

  Incidence of solicited adverse events after the third dose vaccination (Applicable for Infants)

  Day 0 to 7 after the third dose vaccination

• Safety index-incidence of solicited adverse events

  Incidence of solicited adverse events after the booster dose (Applicable for Toddlers and Children)

  Day 0 to 7 after the booster dose

• Safety index-incidence of unsolicited adverse events

  Incidence of unsolicited adverse events after the first dose vaccination (Applicable for Infants)

  Day 0 to 30 after the first dose vaccination

• Safety index-incidence of unsolicited adverse events

  Incidence of unsolicited adverse events after the second dose vaccination (Applicable for Infants)

  Day 0 to 30 after the second dose vaccination

• Safety index-incidence of unsolicited adverse events

  Incidence of unsolicited adverse events after the third dose vaccination (Applicable for Infants)

  Day 0 to 30 after the third dose vaccination

• Safety index-incidence of unsolicited adverse events

  Incidence of unsolicited adverse events after the booster dose (Applicable for Toddlers and Children)

  Day 0 to 30 after the booster dose

• Safety index-incidence of adverse events

  Occurrence of adverse events after vaccination

  From the beginning of the vaccination up to 30 days after the last vaccination completed

Secondary Outcomes (21)

• Safety index-incidence of serious adverse events

  From the beginning of the vaccination up to 12 months after the last vaccination completed

• Immunogenicity index-seroconversion or ≥4-fold increase rates of antibody against DT

  Between baseline and Day 30 after vaccination

• Immunogenicity index-seroconversion or ≥4-fold increase rates of antibody against TT

  Between baseline and Day 30 after vaccination

• Immunogenicity index-seroconversion or ≥4-fold increase rates of antibody against PT

  Between baseline and Day 30 after vaccination

• Immunogenicity index-seroconversion or ≥4-fold increase rates of antibody against FHA

  Between baseline and Day 30 after vaccination

Other Outcomes (34)

• Immunogenicity index-seropositive rates of neutralizing antibody against DT

  Day 30 after vaccination

• Immunogenicity index-seropositive rates of neutralizing antibody against PT

  Day 30 after vaccination

• Immunogenicity index-seropositive rates of neutralizing antibody against FHA

  Day 30 after vaccination

Study Arms (11)

Intervention (Children aged 6 years, one-dose)

EXPERIMENTAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine in Children aged 6 years on Day 0

Biological: DTacP (one-dose booster)

DT Control (Children aged 6 years, one-dose)

ACTIVE COMPARATOR

Diphtheria-Tetanus Combined Vaccine in Children aged 6 years on Day 0

Biological: DT (one-dose booster)

Intervention (Toddlers aged 18-24 months, one-dose)

EXPERIMENTAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine in toddlers aged 18-24 months on Day 0

Biological: DTacP (one-dose booster)

DTaP Control (Toddlers aged 18-24 months, one-dose)

ACTIVE COMPARATOR

Diphtheria-Tetanus-acellular Pertussis Vaccine in toddlers aged 18-24 months on Day 0

Biological: DTaP (one-dose booster)

PENTAXIM Control (Toddlers aged 18-24 months, one-dose)

ACTIVE COMPARATOR

PENTAXIM (DTaP-IPV-Hib) Vaccine in toddlers aged 18-24 months on Day 0

Biological: PENTAXIM (one-dose booster)

Intervention (Infants aged 3 months, three-dose)

EXPERIMENTAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine in infants aged 3 months on an M3-M4-M5 immunization schedule

Biological: DTacP (three-dose primary vaccination)

DTaP Control (Infants aged 3 months, three-dose)

ACTIVE COMPARATOR

Diphtheria-Tetanus-acellular Pertussis Vaccine in infants aged 3 months on an M3-M4-M5 immunization schedule

Biological: DTaP (three-dose primary vaccination)

PENTAXIM Control (Infants aged 3 months, three-dose)

ACTIVE COMPARATOR

PENTAXIM (DTaP-IPV-Hib) Vaccine infants aged 3 months on an M3-M4-M5 immunization schedule

Biological: PENTAXIM (three-dose primary vaccination)

Intervention (Infants aged 2 months, three-dose, 2-3-4)

EXPERIMENTAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine in infants aged 2 months on an M2-M3-M4 immunization schedule

Biological: DTacP (three-dose primary vaccination)

Intervention (Infants aged 2 months, three-dose, 2-4-6)

EXPERIMENTAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine in infants aged 2 months on an M2-M4-M6 immunization schedule

Biological: DTacP (three-dose primary vaccination)

PENTAXIM Control (Infants aged 2 months, three-dose)

ACTIVE COMPARATOR

PENTAXIM (DTaP-IPV-Hib) Vaccine infants aged 2 months on an M2-M3-M4 immunization schedule

Biological: PENTAXIM (three-dose primary vaccination)

Interventions

DTacP (one-dose booster) BIOLOGICAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine of 0.5mL on Day 0

Intervention (Children aged 6 years, one-dose); Intervention (Toddlers aged 18-24 months, one-dose)

DTacP (three-dose primary vaccination) BIOLOGICAL

Diphtheria-Tetanus-acellular Pertussis Component Combined Vaccine of 0.5mL on the M3-M4-M5, M2-M3-M4, or M2-M4-M6 immunization schedule

Intervention (Infants aged 2 months, three-dose, 2-3-4); Intervention (Infants aged 2 months, three-dose, 2-4-6); Intervention (Infants aged 3 months, three-dose)

DT (one-dose booster) BIOLOGICAL

Diphtheria-Tetanus Combined Vaccine of 0.5mL on Day 0

DT Control (Children aged 6 years, one-dose)

DTaP (one-dose booster) BIOLOGICAL

Diphtheria-Tetanus-acellular Pertussis Vaccine of 0.5mL on Day 0

DTaP Control (Toddlers aged 18-24 months, one-dose)

PENTAXIM (one-dose booster) BIOLOGICAL

Diphtheria, Tetanus, acellular Pertussis, inactivated Polio, conjugate Haemophilus influenzae type b Combined Vaccine of 0.5mL on Day 0

PENTAXIM Control (Toddlers aged 18-24 months, one-dose)

DTaP (three-dose primary vaccination) BIOLOGICAL

Diphtheria-Tetanus-acellular Pertussis Vaccine of 0.5mL on an M3-M4-M5immunization schedule

DTaP Control (Infants aged 3 months, three-dose)

PENTAXIM (three-dose primary vaccination) BIOLOGICAL

Diphtheria, Tetanus, acellular Pertussis, inactivated Polio, conjugate Haemophilus influenzae type b Combined Vaccine of 0.5mL on the M3-M4-M5 or M2-M3-M4 immunization schedule

PENTAXIM Control (Infants aged 2 months, three-dose); PENTAXIM Control (Infants aged 3 months, three-dose)

Eligibility Criteria

• Age: 2 Months - 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age Requirement: children aged 6 years, toddlers aged 18-24 months, and infants aged 2-3 months at the time of enrollment
• Previous Vaccination Requirements: (a) Children (aged 6 years) enrolled in the study should have received four doses of the Diphtheria, Tetanus, and Pertussis combined vaccine, and not yet received the Diphtheria, Tetanus combined vaccine; (b) Toddlers (aged 18-24 months) enrolled in the study should have received three doses of Diphtheria, Tetanus, and Pertussis combined vaccine as well as three doses of the Polio vaccine, and not yet received the booster dose of Diphtheria, Tetanus, and Pertussis combined vaccine and the Polio vaccine; (c) Infants (aged 3 months) enrolled in the study should not have received diphtheria-tetanus-pertussis-containing vaccine, polio-containing vaccine, 13-valent pneumococcal polysaccharide conjugate vaccine, Haemophilus influenzae type b conjugate vaccine, or meningococcal group A and C polysaccharide conjugate vaccine; (d) Infants (aged 2 months) enrolled in the study should not received diphtheria-tetanus-pertussis-containing vaccine, polio-containing vaccine, 13-valent pneumococcal polysaccharide conjugate vaccine, or Haemophilus influenzae type b conjugate vaccine.
• Provision of Legal Identification: Volunteers and their legal guardians or appointed representatives must provide valid legal identification documents.
• Informed Consent: Legal guardians or appointed representatives of volunteers must have the capacity to understand the informed consent document and the research process, voluntarily participate, sign the informed consent form, and be able to comply with the requirements in the study as well as complete relevant visits on time.
• Birth Outcome Condition: Toddlers (aged 18-24 months) and Infants (aged 2-3 months) should be born at full term (37-42 weeks of gestation) with birth weight ≥2500g.
• Temperature Requirement: Axillary body temperature is no more than 37.3°C.

You may not qualify if:

• Previous Diagnosis: Subjects diagnosed with pertussis, tetanus, or diphtheria disease.
• Special Conditions for Toddlers (aged 18-24 months) and Infants (aged 2-3 months): Subjects have been with abnormal labor (dystocia, instrumental delivery) or a history of asphyxia, nervous system damage, or clinically confirmed pathological jaundice.
• Allergic History: Subjects have a history of allergies to any component of the vaccine (such as aluminum hydroxide), or previous allergy or suspected allergy to any vaccine, or other serious adverse reactions, such as anaphylactic shock, laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, local anaphylactic necrosis reaction, dyspnea, angioedema, systemic rash and/or urticaria.
• Vaccination History: Subjects received any inactivated vaccines or subunit vaccines within 7 days before vaccination (except COVID-19 vaccines) with the investigational vaccine, or any other live attenuated vaccines or COVID-19 vaccines within 14 days before vaccination
• Acute Illness: Subjects have acute illness (e.g., fever) or acute exacerbation of a chronic illness within 3 days before receipt of the first dose of the investigational vaccine
• Neurological and Mental Health: Subjects have a history or family history of seizures, epilepsy, and other encephalopathy and psychiatric disorders.
• Health Condition: Subjects have a major congenital malformation, developmental disability, or congenital disease (e.g., Down syndrome, sickle cell anemia, congenital neurological disorders), or other clinically diagnosed serious chronic disease, including but not limited to, serious diseases of the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolic system, skeletal system and other system and malignant tumor history.
• Blood Disease: Subjects have genetic bleeding tendency or coagulopathy, or a history of bleeding disorders.
• Infectious Disease: Subjects diagnosed with infectious diseases that may interfere with the study, such as tuberculosis, viral hepatitis, human immunodeficiency virus (HIV) infection, etc.
• Special Condition: Subjects who cannot tolerate venipuncture or have a history of needle and blood sickness.
• Organ Removal History: Subjects with surgical removal of the spleen or other vital organs for any reason.
• Blood Condition: Subjects with blood loss (≥400 ml) and receipt of blood or blood products in the 3 months before receipt of the first dose of the investigational vaccine
• Immune Therapy: Subjects received treatment with an immunosuppressive agent, such as long-term systemic glucocorticoid therapy (treatment with systemic glucocorticoids, such as prednisone or a similar agent, for more than 2 consecutive weeks within 6 months before receipt of the first dose of an investigational vaccine), except topical agents (such as ointments, eye drops, inhalers, or nasal sprays) that do not exceed the recommended dose in the label or have any signs of systemic exposure
• Participation in Other Clinical Studies: Subjects use any investigational or unregistered product (drug, biologic product, or device) within 3 months before receipt of the first dose of the investigational vaccine, plan to use such product during the duration of this study, or were enrolled in another clinical trial before enrollment in this study.
• Physical Examination: (a) Subjects with abnormal vital signs with clinical significance; (b) Subjects abnormal blood routine, blood biochemistry, and urine routine test indicators with clinical significance

Sponsors & Collaborators

• Institute of Medical Biology, Chinese Academy of Medical Sciences: lead
• Sichuan Center for Disease Control and Prevention: collaborator

Study Sites (3)

Dazhu Center for Disease Prevention and Control

Dazhou, Sichuan, China

RECRUITING

Cuiping Center for Disease Prevention and Control

Yibin, Sichuan, China

NOT YET RECRUITING

Xingwen Center for Disease Prevention and Control

Yibin, Sichuan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Diphtheria; Tetanus; Whooping Cough

Interventions

Immunization, Secondary; Pentavac

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

Intervention Hierarchy (Ancestors)

Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Central Study Contacts

Jingsi Yang

CONTACT

0871-68334551; yjs@imbcams.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: In this study, participants are blinded, and part of the investigators are blinded.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three stages (Children, Toddlers, and Infants) will be conducted according to the age-escalating principle. If safety assessed by DSMB meets the criteria, then the enrollment of the next stage could be continued.

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: December 28, 2023
• Study Start: December 23, 2023
• Primary Completion: December 15, 2024
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 3, 2024

Record last verified: 2024-01

Locations

CN (3)