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

Phase 2

Completed

Brief Summary: 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.

Detailed 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

Recruitment & Eligibility

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

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Cervical Ripening Rate, Measured by Bishop Score - Slope	Daily measures of Bishop Score from start of study drug administration until delivery (up to 7 days).	Cervical ripening rate during up to the first seven days of treatment, measured by Bishop Score - Slope. Bishop score is an Assessment of the cervical stage by its: dilatation, position, effacement and consistency. The score was calculated as the sum of the following 5 categories where each category is scored between 0-2: * Fetal station (0-2) * Cervical diameter at inner meatus (0-2) * Cervical effacement (0-2) * Consistency at inner meatus (0-2) * Cervical position (0-2) Graded from 0-10, Bishop score of ≤ 4 is unripe and ≥ 6 is ripe. Bishop score was measured daily from start of treatment up until 7 days. The cervical ripening rate was calculated from the slope of the curve (score/day) when plotting Bishop score against days of treatment.

Secondary Outcome Measures

Name	Time	Method

Locations (7): Förlossningsavdelningen Akademiska Universitetssjukhuset
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Uppsala, Sweden
Naistenklinikka (HUS)
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Helsinki, Finland
Lund University Hospital
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Lund, Sweden
Kvinnokliniken Södersjukhuset
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Stockholm, Sweden
Kvinnokliniken Universitetssjukhuset Linköping
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Linköping, Sweden
Tampere University Hospital
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Tampere, Finland
Kvinnokliniken Skaraborgs Sjukhus
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Skövde, Sweden