Treatment With the Anti-IgE Monoclonal Antibody Omalizumab in Women With Asthma Undergoing Fertility Treatment. - A Proof of Concept Study.

NCT03727971 | Completed Phase 2 DMC

• 2 other identifiers: 2018-001137-41H-18016605
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators have previously confirmed a clinical hunch that women with asthma have difficulties in becoming pregnant. The investigators found increased time to pregnancy (TTP) in women with asthma compared to non-asthmatic women (55 vs 33 months, p\<0.001), furthermore, women with asthma had less successful pregnancies following fertility treatment (39.6 vs 60.4%, p=0.002). Treatment with omalizumab stabilizes the eosinophilic disease, through the systemic and most likely the anti-inflammatory pathways, which indicate a promising possibility to increase pregnancy rate. In a small real-life study in 2017, 5 patients with eosinophilic asthma who underwent in vitro fertilization (IVF), were treated with omalizumab prior to embryo transplantation; three out of the five women became pregnant. Lastly, the two remaining patients had several treatments with omalizumab, but did not become pregnant. This real-life study calls for further investigation. By targeting systemic inflammation with omalizumab treatment the aim is to increase asthma control before and during pregnancy. A treatment strategy aiming at improving overall inflammatory control may increase fertility, but also reduce well known maternal and perinatal adverse pregnancy outcomes such as pregnancy loss, preeclampsia, gestational diabetes, low-birth weight, small for gestational age (SGA), preterm delivery. Study design: A randomized control trial with omalizumab and placebo, stratified for blood eosinophil count, is therefore needed. A randomized, double blinded, parallel group, study to evaluate the difference between omalizumab (O) and placebo (P) on pregnancy rate in patients with atopic asthma.Treatment schedule: After collection of material (blood samples, sputum) 6th day (±1 day) of the menstrual cycle, the patients will be randomized in either the omalizumab group or the placebo group. No collection of material will be done at the time of enrollment, as this will be on different time of the female cycles. The treatment is initiated with one injection with weight and serum-immunglobulin E balanced omalizumab or one injection placebo. After omalizumab treatment at ovulation it will again be collected material (blood samples, sputum). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred. Outcome: The primary out-come is efficacy of omalizumab, compared to placebo, in increasing pregnancy rate in females with asthma. Secondary out-comes are changes in the inflammation in lungs/systemic, pregnancy loss, asthma control and biomarkers in the blood/lungs.

Conditions

Asthma; Infertility, Female

Outcome Measures

Primary Outcomes (1)

• Pregnancy rate

  To explore differences in pregnancy rate between asthmatic women receiving biological treatment vs. asthmatic women receiving normal asthma treatment and placebo. Pregnancy rate is defined as positive serum- Choriogonadotropin (in week 2) and ongoing pregnancy confirmed with ultra sound in week 7, after 3 consecutive IVF cycles. End of study measured as birth of life born infant or unsuccessful pregnancy

  7 weeks

Secondary Outcomes (11)

• Inflammation - degree of inflammation in sputum and blod before and after intervention

  12 months

• Rate of miscarriages in both groups.

  9 months

• Differens in time to pregnancy between the two groups

  12 months

• Change in C-reactive-protein concentration before and after intervention

  6 months

• Change in Immunoglobulin E concentration before and after intervention

  6 months

Study Arms (2)

omalizumab arm

ACTIVE COMPARATOR

The treatment is initiated with one injection with weight and serum-Immunoglobulin E balanced omalizumab one time per cyclus

Drug: Omalizumab Injection

placebo arm

PLACEBO COMPARATOR

Participants will be administered placebo (NaCl), one time per cyclus

Drug: NaCl

Interventions

Omalizumab Injection DRUG

The treatment is initiated with one injection with weight and serum-immunoglobulin E balanced omalizumab. After omalizumab treatment at ovulation it will again be collected material (blood samples, sputum, secretion of the vagina, secretion of the rectum, secretion of the uterus, microbiota). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred.

omalizumab arm

NaCl DRUG

The treatment is initiated with one injection with placebo. After placebo injection treatment at ovulation it will again be collected material (blood samples, sputum, secretion of the vagina, secretion of the rectum, secretion of the uterus, microbiota). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred.

placebo arm

Eligibility Criteria

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

You may qualify if:

• \* Informed consent
• Diagnosis of asthma
• Infertility due to male factor infertility, tubal factor infertility or unexplained infertility.
• Referred to IVF treatment with or without ICSI
• Willingness to receive treatment with biologic drugs during menstruation period
• Controlled disease with an ACQ ≤ 1.5

You may not qualify if:

• Other respiratory diseases than asthma
• Other inflammatory disease or a disease that affects fertility.
• Allergy to the investigational drugs
• Respiratory infections requiring antibiotics or anti-viral treatment within 30 days
• TESA / TESE, endometriosis
• Infertility due to other reasons than male factor, tubal factor or unexplained infertility

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Novartis: collaborator
• Hvidovre University Hospital: collaborator
• Herlev Hospital: collaborator
• Zealand University Hospital: collaborator

Study Sites (1)

Charlotte Suppli Ulrik

Copenhagen, DK-2100, Denmark

Location

Related Publications (1)

• Tidemandsen C, Juul Gade E, Ulrik CS, Nielsen HS, Oxlund-Mariegaard BS, Kristiansen K, Freiesleben NC, Nohr B, Udengaard H, Backer V. Treatment with the anti-IgE monoclonal antibody omalizumab in women with asthma undergoing fertility treatment: a proof-of-concept study-The PRO-ART study protocol. BMJ Open. 2020 Nov 12;10(11):e037041. doi: 10.1136/bmjopen-2020-037041.

  PMID: 33184076 DERIVED

MeSH Terms

Conditions

Asthma; Infertility, Female

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All packaging and labeling of the biological drugs and placebo will be done in a way that ensures blinding for the investigator site staff. Glostrup pharmacy, the hospital pharmacy at the Capital region, will manage randomization and blinding. Participants will be randomized in two equally big groups, one receiving omalizumab and one receiving placebo, by a computer based program, blinded to investigator. It will be randomized to blocks of 10, in total 16 blocks. It will be automated random assignment of subject numbers to randomization numbers. These randomization numbers are linked to the different treatment arms, which in turn are linked to medication numbers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A randomized, double blinded, parallel group, study

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: November 1, 2018
• Study Start: January 1, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Juni 2030 - for 10 years

Locations

DK (1)