Immunomodulatory Therapy to Restore Ovarian Function and Improve Fertility in Women With Autoimmune Premature Ovarian Insufficiency

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexFemale
Age18-38
SponsorAngelica Lindén Hirschberg

About this trial

Several autoimmune diseases such as Addison's disease are associated with failing ovarian function, known as premature ovarian insufficiency (POI), which can lead to early menopause and reduced fertility.The underlying cause of POI in these women is considered to be an immunological attack on the ovaries that causes them to not respond to hormonal stimulation from the brain. Hormone replacement effectively counteracts menopausal symptoms, but today there is no treatment to normalize or even improve fertility. As a patient with POI and an autoimmune diagnosis and the desire to become pregnant, you are asked to participate in the study. The aim of this study is to investigate whether immunomodulatory therapy can improve and ideally normalize ovarian function in women of childbearing age with autoimmune disease and proven POI. Patients with a male partner and a desire for children and who respond positively to the first ovarian stimulation will be offered in vitro fertilization (IVF) and will thus be allowed to complete the study. Other participating patients will undergo a total of three ovarian stimulations and treatment with first two infusions of the registered drug rituximab or placebo (inactive agent) and later two additional infusions where all patients receive rituximab. The first two infusions with rituximab or placebo are double-blind, which means that neither you nor the study staff know what you have received. Follow-up takes place up to 12 months after the last infusion.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

The subject has given their written consent to participate in the trial

Autoimmune POI (FSH > 25 IU/L) including the presence of oligo/amenorrhea lasting at least 4 months, and elevated FSH levels (FSH > 25 IU/L) confirmed on two separate occasions, with measurements taken at least 4 weeks apart and Addison's disease or ab positivity for 21-hydroxylase or other relevant autoantibodies (SCC, 17-OH, NALP5)

18-38 years of age

Body mass index between 19-30

Disqualifiers

Hypersensitivity to rituximab, any of the AxMPs, or any of the excipients (as detailed in the SmPC for the various IMPs)

Active, severe infection or JCV positivity

Active hepatitis B infection

Severe immunosuppression

Trial design

Design model

Crossover

Treatments tested in this trial

  • Rituximab (Arm A)

    Drug

    Total 4 infusions (4 g) of Rituximab

  • Rituximab (Arm B)

    Drug

    2 infusions (2 g) of Rituximab

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Group A 2 infusions with placebo or Rituximab, and then 2 infusions of RituximabActive comparator 1 intervention
Group B: Group B , 2 infusions (2 g) RituximabActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Egg retrieval in response to controlled ovarian hyperstimulation

Egg retrieval (yes/no) in response to controlled ovarian hyperstimulation at 4 to 6 months after rituximab treatment compared to placebo.

Time frame
4 to 6 months after rituximab/placebo treatment.

Secondary outcomes

1

Occurrence of spontaneous menstrual bleeding

Occurrence of spontaneous menstrual bleeding (yes/no) at any point during the 19-month study period.

Time frame
19-month study period from baseline to end of study.
2

Proportion of participants who achieve ovulation

Proportion of participants who achieve ovulation (defined as serum progesterone \>10 nmol/L) at any time during the study period.

Time frame
During 19 months from baseline to end of study.
3

Changes in serum follicle-stimulating hormone

Changes in serum follicle-stimulating hormone (FSH) IE/L levels from baseline to the end of the study period.

Time frame
From baseline to the end of the study period (19 months).
4

Change in serum anti-Mullerian hormone

Changes in serum anti-Mullerian hormone (AMH) microgram/L levels from baseline to the end of the study period.

Time frame
From baseline to the end of the study period (19 months).

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Angelica Lindén Hirschberg

Lead sponsor

Karolinska University Hospital

Sponsor institution