Immunomodulatory Therapy in Women With Autoimmune Premature Ovarian Insufficiency

Autoimmune Diseases Clinical Trial

Official title:

Effects of Immunomodulatory Therapy on Gonadal Function in Women With Autoimmune Premature Ovarian Insufficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05586737
• Other study ID #: KarolinskaUniversityHospital
• Status: Recruiting
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: December 2024

Study information

• Verified date: October 2022
• Source: Karolinska University Hospital
• Contact: Angelica L Hirschberg, MD, PhD
• Phone: +46 70 255 99 24
• Email: angelica.linden-hirschberg[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. Reestablishment of spontaneous menstrual bleedings during the 12 months' study period

2. Ovulation during the 12 months' study period

3. Change in B-cell count, autoantibody indices and immunoglobulin levels (IgG) after treatment

Safety outcomes: All adverse events. Of particular relevance are any hospital admissions, infections and allergic reactions.

Study population: Fifteen women with autoimmune POI defined as absence of menstruation > 6 months and elevated serum level of follicle stimulation hormone > 40 International units (IU)/L.

Inclusion criteria: Autoimmune POI defined as presence of autoantibodies against 21-hydroxylase (OH), side chain cleavage enzyme (SCC), 17-OH and/or neuronal apoptosis inhibitory protein (NACHT) leucine-rich-repeat protein 5 (NALP5) or other relevant autoantibodies; 18-35 yrs of age; body mass index 19-30.

Exclusion criteria: Hypersensitivity to rituximab; severe infection; severe immunosuppression; cardiac disease; cancer; benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst; vaginal bleeding of unknown aetiology.

Time plan: The study is expected to start the spring 2017. It is expected to be closed spring 2023.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Autoimmune premature ovarian insufficiency defined as presence of autoantibodies against 21-OH, SCC, 17-OH and/or NALP5 or other relevant autoantibodies

2. 18-35 yrs of age

3. Body mass index 19-30.

4. In fertile females, willingness to comply with effective contraceptive methods.

5. Ability to provide informed consent

Exclusion Criteria:

1. Documented hypersensitivity or intolerance to rituximab

2. Active, severe infection

3. Severe immunosuppression

4. Severe cardiac disease

5. Cancer

6. Benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst

7. Vaginal bleeding of unknown aetiology

8. Hormone replacement therapy (HRT) within four weeks prior study entry.

9. Pregnant or lactating women

10. Concurrent treatment with other immunosuppressive drugs

11. Vaccination within 4 weeks of infusion of study medication

12. Severe psychiatric disorder

13. Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with Rituximab.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Menopause, Premature
• Premature Birth
• Premature Ovarian Insufficiency
• Primary Ovarian Insufficiency

Intervention

Drug:
• Rituximab
1 gram rituximab twice with two weeks interval

Locations

Country	Name	City	State
Sweden	Angelica Hirshberg	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Angelica Lindén Hirschberg

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.	Vaginal ultrasound measurement	4 months
Primary	The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion.	Vaginal ultrasound measurement	4 months
Secondary	Spontaneous menstrual bleedings during the 12 months' study period	Number of spontaneous menstrual bleedings	12 months
Secondary	Ovulation during the 12 months' study period	Confirmed ovulation (y/n)	12 months
Secondary	Immunoglobulin levels	Change in immunoglobulin levels (g/L) from baseline	4 and 12 months