Certolizumab in Recurrent Implantation Failure (RIF)

NCT05930613 | Recruiting Phase 3

• 2 other identifiers: APHP2000312021-005309-28
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent implantation failure (RIF), defined as the absence of clinical pregnancy after the transfer of three good-quality embryos, concerns up to 40% of IVF couples and is associated with a low success rate. The causes remain unexplained in over 50% of cases. Various dysimmune changes (related to immune T cells profiles, pro-inflammatory cytokines levels) have been described in unexplained RIF as compared to fertile controls, and it has been estimated that such dysimmunity may occur in 50% of unexplained RIFs. Previous data on a benefit of general immune modulation by steroids or immunoglobulins are heterogenous and failed to demonstrate clinically significant benefit. The proinflammatory cytokine Tumor Necrosis Factor (TNF) α participates in the regulation of the immune balance of the endometrium, its peripheral blood and endometrial concentrations are increased in RIF patients as compared to fertile controls. In 2009, a pilot placebo controlled study showed that TNF-α antagonist treatment allowed a 56% live birth rate (versus 13% in controls) in 13 women with unexplained RIF. Due to the lack of maternal and fetal tolerance data, TNF-α antagonists were not further evaluated. Today, safety data issued from 1200 pregnancies are reassuring allowing the use of TNF-α antagonists during pregnancy (www.lecrat.org). In addition the TNF-α antagonist certolizumab does not cross the placental barrier. We hypothesize that certolizumab may improve clinical pregnancy rates in women with unexplained RIF with a good safety profile.

Conditions

Recurrent Unexplained Implantation Failure

Keywords

Recurrent Implantation Failure; Immunomodulation; Anti-TNF-α; Certolizumab; Pregnancy

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy defined as the presence of cardiac activity on ultrasound scan

  Presence of cardiac activity on ultrasound scan at 5 weeks +/- 6 days of gestation

  5 weeks +/- 6 days of gestation

Secondary Outcomes (3)

• Live birth

  22 to 40 weeks of gestation

• Miscarriage

  Before 12 weeks of gestation

• All adverse events distinguishing serious adverse events

  Through study completion, a maximum of 64 months and 3 weeks

Study Arms (2)

1

EXPERIMENTAL

Certolizumab (CIMZIA® ; TNF-α antagonist )

Drug: Certolizumab (CIMZIA® ; TNF-α antagonist)

2

PLACEBO COMPARATOR

Placebo (NaCl 0.9 % solution)

Drug: Placebo (NaCl 0.9 % solution)

Interventions

Certolizumab (CIMZIA® ; TNF-α antagonist) DRUG

400mg of certolizumab injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.

1

Placebo (NaCl 0.9 % solution) DRUG

NaCl 0,9% injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.

2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-40 years
• Idiopathic, male or tubal factor infertility
• Unexplained recurrent implantation failure defined as consecutive failure to obtain clinical pregnancy after at least transfers of 3 good-quality embryos (Istanbul criteria)
• Affiliation to a French social security system (beneficiary or legal)
• Informed and signed consent

You may not qualify if:

• Known cause of RIF among the following:
• Genetic parental anomalies
• Non-gestational diabetes mellitus of type I and II,
• Infectious disease
• Antiphospholipid syndrome
• Sickle cell disease
• Diffuse adenomyosis
• No contraindication to Freeze-thaw embryo transfer (FET) treatment
• Linked to certolizumab:
• Hypersensitivity to the active substances or to any of the excipients
• Primary or secondary immunodeficiency (history of or currently active)
• Active uncontrolled infection
• Active tuberculosis
• Cardiac insufficiency (moderate to severe, New York Heart Association (NYHA) III/IV classes)
• Any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Saint-Antoine Hospital - APHP

Paris, 75012, France

RECRUITING

MeSH Terms

Interventions

Certolizumab Pegol; Solutions

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Study Officials

• Arsene MEKINIAN, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathalie CHABBERT-BUFFET, Pr

CONTACT

01 56 01 55 10; nathalie.chabbert-buffet@aphp.fr

KOLANSKA Kamila, Dr

CONTACT

01 56 01 68 69; kamila.kolanska@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: July 5, 2023
• Study Start: November 30, 2023
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)