E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune premature ovarian insufficiency |
|
E.1.1.1 | Medical condition in easily understood language |
Premature ovarian insufficiency (POI) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052660 |
E.1.2 | Term | Hypergonadotropic hypogonadism |
E.1.2 | System Organ Class | 100000004860 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study if rituximab therapy can improve ovarian response to gonadotropin stimulation in women with autoimmune POI. |
|
E.2.2 | Secondary objectives of the trial |
• To investigate if rituximab therapy can improve menstrual function and restore ovulation
•To study the immunological response by the treatment and AMH as a marker for the ovarian reserve |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 years of age
3. body mass index 19-30
4. Willingness to comply with effective non-hormonal contraceptive methods upto 12 months after the last infusion
5. Ability to provide informed consent |
|
E.4 | Principal 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, s-HCG/u-HCG
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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events. Of particular relevance are any hospital admissions, infections and allergic reactions. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the study period of one year for each patient. |
|
E.5.2 | Secondary end point(s) |
Mid assessment at month 2 and 8: blood sample, pregnancy test, vital signs and adverse events.
Post treatment assessment at month 4: blood sample, pregnancy test, gynecological assessment with ultrasound, controlled ovarian hyperstimulation, vital signs and adverse events.
End assessment at month 12 : blood sample, pregnancy test, vital signs and adverse events. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Mid assessment at month 2 and 8
Post treatment assessment at month 4
End assessment at month 12 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |