A Phase I Trial Evaluate the Safety and Tolerability Profile of HPV Vaccine
Condition: Human Papillomavirus Infection
MeSH terms: Papillomavirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is to evaluate the safety and tolerability profile of Recombinant Nonavalent
      (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli) in
      healthy women ages 18-45
    

Detailed description: 
      This is a single-centre, dose-escalating, randomized, blinded and active controlled trial in
      healthy Chinese women ages 18-45. The positive control is Recombinant nonavalent Human
      Papillomavirus (Types 6,11,16,18,31,33,45,52,58) Vaccine.

      The trial will be conducted in two stages:

      Stage 1: A single-center, open-label trial will be carried out in 40 healthy women ages 27-45
      in the enrolment order of mid-dosage group followed by high-dosage group. Each group of 20
      subjects will be administered the mid-, and high-dosage form, respectively, to preliminarily
      evaluate the safety profile of the investigational vaccine.

      First, the 20 subjects in the mid-dosage group will be sequentially enrolled as two batches
      of 5 and 15 subjects, respectively, at an enrolment interval of no less than 3 days. One week
      after vaccinating all the 20 subjects in the mid-dosage group, upon confirmation of the
      safety profile of the investigational vaccine as acceptable, 20 subjects for the higher
      dosage-group will be enrolled subsequently in the same manner as those in the mid-dosage
      group.

      Subjects in each dosage group will receive a 3-dose regimen at months 0, 2 and 6. Safety of
      the investigational vaccine will be assessed for 30 days following each injection, and SAE
      will be reported for the duration of the study. In total there will be 12 scheduled visits
      for subjects in each dosage group throughout the study.

      One week after vaccinating all the 40 subjects in stage 1, if the safety profile of the
      investigational vaccine is confirmed to be acceptable, the study may proceed to stage 2.

      Stage 2:

      A phase I, single-center, dose-escalating, randomized and blinded (as to intra-dosage group)
      trial, with Gardasil9 as the positive control will be carried out in 120 healthy women ages
      18-26 in the enrolment order of low-, mid-, and high-dosage groups. Each group of 40 subjects
      will be enrolled and randomized at a 3: 1 ratio to receive the investigational vaccine or
      positive control, respectively (that is, 10 of the subjects in each dosage group will receive
      the positive control).

      Firstly, the 40 subjects in the low-dosage group will be sequentially enrolled as four
      batches of 5, 10, 10 and 15 subjects, respectively, at an enrolment interval of no less than
      3 days to get the first dose of the low-dosage investigational vaccine or positive control.
      Then, one week after vaccinating all the 40 subjects in the low-dosage group, upon
      confirmation of the safety profile of the investigational vaccine as acceptable, 40 subjects
      will be enrolled subsequently into the mid-dosage group in the same manner as those in the
      low-dosage group. Again, one week after vaccinating the 40 subjects in the mid-dosage group,
      if the safety profile of the investigational vaccine continues to be acceptable, another
      group of 40 subjects receiving the high-dosage investigational vaccine or positive control
      will be enrolled subsequently in the same manner as those in the low-dosage group.

      In both stage 1 and stage 2 of the phase I study, 5 ml of non-anticoagulative blood will be
      collected from trial subjects prior to dose 1 and at Month 3 and Month 7 post dose 1 to
      determine the levels of neutralizing antibodies and IgG antibodies to the vaccine HPV types.
    

Intervention name(s): Recombinant Nonavalent (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli); Recombinant nonavalent Human Papillomavirus (Types 6,11,16,18,31,33,45,52,58) Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): For Low-dosage group, a 3-dose regimen administered at months 0, 2 and 6. For Mid-dosage group, a 3-dose regimen administered at months 0, 2 and 6. For High-dosage group, a 3-dose regimen administered at months 0, 2 and 6.; A 3-dose regimen administered at months 0, 2 and 6.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The trial will be conducted in two stages:
Stage 1: An open-label trial will be carried out in 40 healthy women ages 27-45 in the enrolment order of mid-dosage group followed by high-dosage group. Each group of 20 subjects will be administered the mid-, and high-dosage form respectively.
Stage 2: A randomized and blinded (as to intra-dosage group) trial, with Gardasil9 as the positive control will be carried out in 120 healthy women ages 18-26 in the enrolment order of low-, mid-, and high-dosage groups. Each group of 40 subjects will be enrolled and randomized at a 3: 1 ratio to receive the investigational vaccine or positive control, respectively.
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: CIN; VIN; VaIN; AIN; Cervical cancer; Vaginal cancer; vulvar cancer; Anal cancer; Genital warts