Effect of Tafoxiparin on Cervical Ripening and Induction of Labor in Term Pregnant Women With an Unripe Cervix

Dilafor

Status and phase: Completed; Phase 2

Conditions: Labor Onset and Length Abnormalities

Treatments: Drug: PL1; Drug: DF01

Study type: Interventional

Funder types: Industry

Identifiers

NCT04000438

PPL17

2019-000620-17 (EudraCT Number)

Details and patient eligibility

About

The study is designed as a randomized, Double-Blind, Placebo-Controlled, Parallel-Group Proof of Concept Study (section A) with a conditional dose finding follow up (Section B) to Evaluate the Efficacy on Cervical ripening, Safety, Tolerability and dose response of Subcutaneously Administered Tafoxiparin in Term Pregnant, Nulliparous Women with an unripe cervix undergoing Labor Induction. If the efficacy and safety profiles of Section A are conclusive in favor of tafoxiparin, the study will continue by adding two additional tafoxiparin dose groups in Section B.

Full description

Primary objective:

To assess the efficacy of tafoxiparin on cervical ripening.

Secondary objective:

To assess the maternal and neonatal safety, tolerability and dose response of tafoxiparin as a supplement therapy in term pregnant, nulliparous women with an unripe cervix undergoing labor induction

Methodology:

Term pregnant, nulliparous women with unripe cervix and planned for labor induction are potential study patients unless enrolled in another study. Subjects may be preinformed about the study through the use of advertisement or information at the physician/midwife visits during pregnancy and at the hospital admission.

The whole study includes the following steps:

Screening and Baseline including informed consent and randomization Study treatment and Induction of Labor Labor Discharge

Enrollment: 365 patients

Sex: Female

Ages: 18 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Pregnant women of ≥18 and ≤ 64 years of age

• Nulliparous

• Unripe cervix with ≤ 4points according to Bishop/Westin score (0-10 points scale)

• Planned for labor induction after 4-7 days of IMP treatment

• Examples of diagnosis as a basis for induction:

  • Post term pregnancy (40-41 weeks of gestation)
  • Gestational diabetes
  • Diabetes type 1 - well controlled
  • Pre-eclampsia (BP diastolic <100, systolic <140)
  • Hypertension - well controlled
  • Hepatosis (without clinically significantly elevated serum bile acids)
  • Maternal age ≥ 40 years
  • Humanitarian-psycho social reasons
  • Oligohydramnios

• Gestational age > 37 weeks confirmed by ultrasound before 21 weeks of gestation

• Singleton pregnancy

• Subject is, as per the discretion of the Investigator, able to comply with the requirements of the protocol including an ability to be present at all required controls

• Subject can understand and sign an informed form

• Provision of written informed consent

Exclusion criteria

• Subjects who are unable to understand the written and verbal instructions in local language
• Breech presentation and other abnormal fetal presentations
• Previous uterine scar
• Spontaneous rupture of membranes at inclusion
• Pathologic CTG at inclusion
• Fetal estimated weight > 2SD of normal fetal estimated weight earlier diagnosed by ultrasound and documented in patient record
• Mother's BMI > 35 at early pregnancy
• Known IUGR defined as ≤ 2SD of normal
• Presence of eclampsia
• Severe Pre-eclampsia
• HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)
• Clinically significant vaginal bleeding in need of hospitalization in the third trimester
• Placenta previa
• Previously known coagulation disorders (Leiden, heterozygote - OK)
• Current use of any drugs that interfere with hemostasis (including heparin /LMWH, direct oral anti-coagulant medication, non-steroidal anti-inflammatory drugs (NSAID) compounds and vitamin K antagonists.)
• Current use of acetylsalicylic acid (ASA) compounds or use within the week preceding inclusion
• Diagnosed with HIV or Acute hepatitis
• Known history of allergy to standard heparin and/or LMWH heparin
• History of heparin-induced thrombocytopenia
• Current drug or alcohol abuse which in the opinion of the Investigator should preclude participation in the study.
• Current participation in other interventional medicinal treatment studies
• Subject has a fear of needles which is believed by the Investigator to affect study medication compliance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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365 participants in 4 patient groups, including a placebo group

Experimental DF01 high dose

Experimental group

Description:

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Treatment:

Drug: DF01

Experimental: DF01 medium dose

Experimental group

Description:

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Treatment:

Drug: DF01

Experimental: DF01 low dose

Experimental group

Description:

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Treatment:

Drug: DF01

Placebo comparator: PL1

Placebo Comparator group

Description:

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Treatment:

Drug: PL1