Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery
Condition: Preterm Birth
MeSH terms: Premature Birth
Intervention: Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL; Vehicle
Intervention description: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.; Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Intervention MeSH terms: 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1740.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 17P; 17-HPC; 17-OHPC; 17-hydroxyprogesterone caproate; progestogens; preterm birth; recurrent preterm birth; spontaneous preterm birth

Summary:

      As part of the continuing effort to study the benefit and risks of 17P and preterm delivery,
      this study is designed as a multi-center, randomized, double-blind, vehicle-controlled
      clinical trial of 17P for the prevention of preterm birth prior to 35 weeks, 0 days of
      gestation in women with a singleton pregnancy, aged 18 years or older, with a previous
      singleton spontaneous preterm delivery. The study also includes a population pharmacokinetic
      (PK) substudy to assess the hydroxyprogesterone caproate (HPC) exposure-response relationship
      and the effect of body mass index (BMI) on the PK of 17P.
    

Eligibility criteria:

        Inclusion Criteria:

        Each subject must meet the following criteria to be enrolled in this study:

          1. Age ≥ 18 years.

          2. Singleton gestation.

          3. Project gestational age 16 weeks 0 days of gestation or more and less than or equal to
             20 weeks 6 days of gestation at the time of randomization, based on clinical
             information and evaluation of the first ultrasound.

          4. Documented history of a previous singleton spontaneous preterm delivery. Spontaneous
             preterm birth is defined as delivery from 20 weeks 0 days to 36 weeks 6 days of
             gestation following spontaneous preterm labor or pPROM. Where possible, the
             gestational age of the previous preterm birth (referred to as the qualifying delivery)
             should be determined as described in "Gestational Age Determination". If the
             gestational age at delivery is obtained directly from the medical record and more than
             one gestational age appears, the latest will be used. As a validation of the
             gestational age of the previous delivery, if the infant weighed more than 3300 grams
             (the birth weight 90th percentile for 36 weeks gestational age), this will not qualify
             as preterm. The previous preterm delivery cannot be an antepartum stillbirth.

        Exclusion Criteria:

          1. Multifetal gestation.

          2. Known major fetal anomaly or fetal demise. An ultrasound examination between 14 weeks
             0 days through 20 weeks 3 days of gestation must be performed to rule out fetal
             anomalies.

          3. Progesterone treatment in any form (i.e., vaginal, oral, intramuscular) during current
             pregnancy, other than micronized progesterone delivered orally or vaginally provided
             it is stopped at least 4 weeks prior to the first dose of study medication.

          4. Heparin therapy during current pregnancy or history of thromboembolic disease.

          5. Maternal medical/obstetrical complications including:

               -  Current or planned cerclage

               -  Hypertension requiring medication

               -  Seizure disorder

          6. Subjects with a uterine anomaly (uterine didelphys or bicornate uterus). However,
             subjects with uterine fibroids are eligible for the study.

          7. Unwillingness to comply with and complete the study.

          8. A 14 weeks 0 days through 20 weeks 3 days of gestation ultrasound cannot be arranged
             before randomization.

          9. Participation in an antenatal study in which the clinical status or intervention may
             influence gestational age at delivery.

         10. Participation in this trial in a previous pregnancy. Women who were screened in a
             previous pregnancy, but not randomized, do not have to be excluded.

         11. Known hypersensitivity to hydroxyprogesterone caproate or its components.

         12. Have any significant medical disorder that, in the opinion of the investigator, would
             be a contraindication to the use of the drug including those listed in section 5.3.2
             of the investigational brochure. Other examples to consider include uncontrolled
             diabetes, known HIV infection or renal dysfunction.

         13. Have any significant medical disorder that, in the opinion of the investigator, would
             preclude accurate evaluation of the subject's condition or outcome in the study.