Immunomodulatory Therapy in Women With Autoimmune Premature Ovarian Insufficiency

• Sponsor: Angelica Lindén Hirschberg (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05586737
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 67.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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. 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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases; Premature Ovarian Insufficiency	Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Immunomodulatory Therapy on Gonadal Function in Women With Autoimmune Premature Ovarian Insufficiency
• Actual Study Start Date: Apr 29, 2019
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rituximab Controlled ovarian hyperstimulation will be performed before and four months after two infusions of 1-gram rituximab (Mabthera®).	Drug: Rituximab; 1 gram rituximab twice with two weeks interval

Outcome Measures

Primary Outcome Measures

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

   Vaginal ultrasound measurement

2. The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion. [4 months]

   Vaginal ultrasound measurement

Secondary Outcome Measures

1. Spontaneous menstrual bleedings during the 12 months' study period [12 months]

   Number of spontaneous menstrual bleedings

2. Ovulation during the 12 months' study period [12 months]

   Confirmed ovulation (y/n)

3. Immunoglobulin levels [4 and 12 months]

   Change in immunoglobulin levels (g/L) from baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Angelica Hirshberg	Stockholm		Sweden

Sponsors and Collaborators

• Angelica Lindén Hirschberg

Investigators

• Study Chair: Olle Kämpe, MD, PhD, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Angelica Lindén Hirschberg, Professor, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT05586737
• Other Study ID Numbers: KarolinskaUniversityHospital
• First Posted: Oct 19, 2022
• Last Update Posted: Oct 24, 2022
• Last Verified: Oct 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Premature Birth; Menopause, Premature; Primary Ovarian Insufficiency; Autoimmune Diseases; Rituximab

Study Results

No Results Posted as of Oct 24, 2022