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

NCT04000438 | Completed Phase 2 Results

• 2 other identifiers: PPL172019-000620-17
• Study Type: interventional
• Target: 365
• Locations: 2 countries
• Sites: 7

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.

Conditions

Labor Onset and Length Abnormalities

Keywords

Priming of labor; Unripe cervix; Home treatment; Cervical ripening; Labor induction

Outcome Measures

Primary Outcomes (1)

• Cervical Ripening Rate, Measured by Bishop Score - Slope

  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.

  Daily measures of Bishop Score from start of study drug administration until delivery (up to 7 days).

Study Arms (4)

Experimental DF01 high dose

EXPERIMENTAL

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

Drug: DF01

Experimental: DF01 medium dose

EXPERIMENTAL

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

Drug: DF01

Experimental: DF01 low dose

EXPERIMENTAL

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

Drug: DF01

Placebo comparator: PL1

PLACEBO COMPARATOR

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

Drug: PL1

Interventions

DF01 DRUG

DF01: The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Also known as: tafoxiparin

Experimental DF01 high dose; Experimental: DF01 low dose; Experimental: DF01 medium dose

PL1 DRUG

DF01: The subject receives sc injections of placebo solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Also known as: Placebo

Placebo comparator: PL1

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Subjects who are unable to understand the written and verbal instructions in local language
• Breech presentation and other abnormal fetal presentations
• Previous uterine scar
• 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.)
• Diagnosed with HIV or Acute hepatitis
• Known history of allergy to standard heparin and/or LMWH heparin

Sponsors & Collaborators

• Dilafor AB: lead

Study Sites (7)

Naistenklinikka (HUS)

Helsinki, 00029, Finland

Location

Tampere University Hospital

Tampere, 33521, Finland

Location

Kvinnokliniken Universitetssjukhuset Linköping

Linköping, 581 85, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Kvinnokliniken Skaraborgs Sjukhus

Skövde, 54185, Sweden

Location

Kvinnokliniken Södersjukhuset

Stockholm, 11883, Sweden

Location

Förlossningsavdelningen Akademiska Universitetssjukhuset

Uppsala, 751 85, Sweden

Location

Results Point of Contact

• Title: Gunvor Ekman-Ordeberg
• Organization: Dilafor AB

gunvor.ekman-ordeberg@dilafor.com

+467060833111

Study Officials

• Gunvor Ekman-Ordeberg, MD, PhD, Study Chair, CMO

  CMO

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 27, 2019
• Study Start: June 21, 2019
• Primary Completion: February 14, 2023
• Study Completion: March 30, 2023
• Last Updated: May 6, 2025
• Results First Posted: April 9, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2); SE (5)