• Time to start of treatment in relation to cervical ripening ≥ 2 points [ Time Frame: From start of study drug administration to cervical ripening (up to 7 days) ]
  Time from start of treatment to increase in Bishop score of ≥ 2 points or spontaneous onset of labor, whichever comes first
• Time to start of treatment in relation to cervical ripening ≥ 3 points [ Time Frame: From start of study drug administration to cervical ripening (up to 7 days) ]
  Time from start of treatment to increase in Bishop score of ≥ 3 points or spontaneous onset of labor, whichever comes first
• Time to start of treatment in relation to cervical ripening ≥ 4 points [ Time Frame: From start of study drug administration to cervical ripening (up to 7 days) ]
  Time from start of treatment to increase in Bishop score of ≥ 4 points or spontaneous onset of labor, whichever comes first
• Time to partus from labor onset [ Time Frame: Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours) ]
  Time from onset of labor to partus. Onset of labor is defined as last record of 4 cm cervical dilatation visualized in the partogram and progress of labor or last record of 4 cm of cervical dilatation in combination with amniotomy and intravenous administration oxytocin
• Time of labor ≤ 6 hours [ Time Frame: Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours) ]
  Proportion of women with established labor ≤ 6 hours
• Time of labor ≥ 12 hours [ Time Frame: Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours) ]
  Proportion of women with established labor ≥ 12 hours
• Dosages of study drug [ Time Frame: From start of study drug administration to cervical ripening (up to 7 days) ]
  Total dosages of study drug (IMP)
• Secondary Safety and tolerability endpoint - adverse event and serious adverse event [ Time Frame: Through study completion (up to 3 days after delivery) ]
  Safety and tolerability will be evaluated through rate and frequency of adverse events and serious adverse events. The AE and SAE will be coded using MedDRA version 19.1.
• Secondary Safety and tolerability endpoint- caesarean sections [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Proportion of patients undergoing caesarean sections (CS)
• Secondary Safety and tolerability endpoint- indications for caesarean sections [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Indications for CS
• Secondary Safety and tolerability endpoint -instrumental deliveries [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Proportion of patients undergoing instrumental deliveries (vacuum extraction (VE)/forceps delivery)
• Secondary Safety and tolerability endpoint- VE and forceps deliveries [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Indications for VE and forceps deliveries
• Secondary Safety and tolerability endpoint- fetal outcome- Birth weight [ Time Frame: From start of study drug administration until delivery ( up to 7 days) ]
  Fetal outcome measured as Birth weight (kg)
• Secondary Safety and tolerability endpoint- fetal outcome -Apgar score [ Time Frame: From start of study drug administration until delivery ( up to 7 days) ]
  Fetal outcome measured as Apgar score (1-10 points). A score > 7 is good health.
• Secondary Safety and tolerability endpoint- fetal outcome - Acidosis and/or Base excess [ Time Frame: From start of study drug administration until delivery ( up to 7 days) ]
  Fetal outcome measured as number of neonatal with Acidosis (pH<7.10) and/or Base Excess < -12 mmol/L arterial or venous in umbilical cord blood
• Secondary Safety and tolerability endpoint - NICU [ Time Frame: From start of study drug administration until delivery (days) ]
  Indication for referral to neonatal intensive care unit (NICU)
• Secondary Safety and tolerability endpoint - NICU [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Proportion of infants staying in the NICU for > 48 hours
• Secondary Safety and tolerability endpoint - tocolytica [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Uterine hyper stimulation in demand of tocolytic treatment
• Secondary Safety and tolerability endpoint - PPH [ Time Frame: From start of study drug administration until delivery (up to 7 days) ]
  Proportion of patients with Postpartum Hemorrhage (PPH) > 2000 ml

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 stuyd 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

• Drug: DF01
  The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until labor induction or spontaneous onset of labor. Induction is done according to clinical practice; 1st balloon, 2nd PGE1
  Other Name: tafoxiparin
• Drug: PL1
  The subject receives sc injections once daily of placebo solution for up to 7 days until labor induction or spontaneous onset of labor. Induction is done according to clinical practice; 1st balloon, 2nd PGE1
  Other Name: Placebo

• Experimental: Experimental DF01 high dose
  The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
  Intervention: Drug: DF01
• Experimental: Experimental: DF01 medium dose
  The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
  Intervention: Drug: DF01
• Experimental: Experimental: DF01 low dose
  The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
  Intervention: Drug: DF01
• Placebo Comparator: Placebo comparator: PL1
  The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
  Intervention: Drug: PL1

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