Immunomodulatory Therapy in Women With Autoimmune Premature Ovarian Insufficiency

NCT05586737 | Completed Phase 2

• 1 other identifier: KarolinskaUniversityHospital
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Title: Effects of immunomodulatory therapy on gonadal function in women with autoimmune premature ovarian insufficiency (POI) Trial objectives and purpose: To study if rituximab therapy can improve ovarian response to gonadotropin stimulation and menstrual function in women with autoimmune POI. Treatment: Controlled ovarian hyperstimulation before and four months after an infusion of 1-gram rituximab (Mabthera®) twice with two weeks interval. Follow-up period 12 months after infusion. Primary outcome: Number of antral follicles and the size of the largest follicle in response to ovarian stimulation. Secondary outcomes:

1. 1.Reestablishment of spontaneous menstrual bleedings during the 12 months' study period
2. 2.Ovulation during the 12 months' study period
3. 3.Change in B-cell count, autoantibody indices and immunoglobulin levels (IgG) after treatment

Conditions

Autoimmune Diseases; Premature Ovarian Insufficiency

Outcome Measures

Primary Outcomes (2)

• Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.

  Vaginal ultrasound measurement

  4 months

• The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion.

  Vaginal ultrasound measurement

  4 months

Secondary Outcomes (3)

• Spontaneous menstrual bleedings during the 12 months' study period

  12 months

• Ovulation during the 12 months' study period

  12 months

• Immunoglobulin levels

  4 and 12 months

Study Arms (1)

rituximab

EXPERIMENTAL

Controlled ovarian hyperstimulation will be performed before and four months after two infusions of 1-gram rituximab (Mabthera®).

Drug: Rituximab

Interventions

Rituximab DRUG

1 gram rituximab twice with two weeks interval

rituximab

Eligibility Criteria

• Age: 18 Years - 35 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Autoimmune premature ovarian insufficiency defined as presence of autoantibodies against 21-OH, SCC, 17-OH and/or NALP5 or other relevant autoantibodies
• yrs of age
• Body mass index 19-30.
• In fertile females, willingness to comply with effective contraceptive methods.
• Ability to provide informed consent

You may not qualify if:

• Documented hypersensitivity or intolerance to rituximab
• Active, severe infection
• Severe immunosuppression
• Severe cardiac disease
• Cancer
• Benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst
• Vaginal bleeding of unknown aetiology
• Hormone replacement therapy (HRT) within four weeks prior study entry.
• Pregnant or lactating women
• Concurrent treatment with other immunosuppressive drugs
• Vaccination within 4 weeks of infusion of study medication
• Severe psychiatric disorder
• Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with Rituximab.

Sponsors & Collaborators

• Angelica Lindén Hirschberg: lead

Study Sites (1)

Angelica Hirshberg

Stockholm, Sweden

Location

MeSH Terms

Conditions

Autoimmune Diseases; Primary Ovarian Insufficiency

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Immune System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Olle Kämpe, MD, PhD

  Karolinska Institutet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 9, 2022
• First Posted: October 19, 2022
• Study Start: April 29, 2019
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)