Treatment of adenomyosis in women of reproductive age.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCDRD Cooperative Clinical Drug Research and Development AG, Nadezhda Reproductive Science OOD

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Decision date (initial)

2026-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nadezhda Reproductive Science OOD

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Others, Pharmacokinetic

To evaluate the effect of valproic acid after a single intralesional administration of valproic acid followed by oral dosing of valproic acid as compared to placebo or a single intralesional administration of valproic acid followed by placebo oral dosing, for the treatment of adenomyosis in reproductive-age women, as measured by the overall effect on pelvic pain documented on a Visual Analog Scale (VAS) and considering the intake of rescue medication.

Secondary objectives 7

1. To assess the effect of each treatment in terms of the reduction of each type of pain type associated with adenomyosis (non-menstrual pelvic pain, dysmenorrhea and/or dyspareunia) as measured by a Visual Analog Scale (VAS).
2. To assess the effect of each treatment on the global assessments of efficacy by patients and investigators using the Patient Global Impression of Change (PGIC) scale, the Clinical Global Impressions (CGI) scale, respectively.
3. To assess the effect of each treatment on the size of the target adenomyosis lesion(s).
4. To assess the effect of each treatment on the menstrual bleeding pattern.
5. To assess the pharmacokinetics of valproic acid after intralesional administration.
6. To assess the pregnancy rate after the first cycle of in vitro fertilization (IVF) performed at least one month after the end of treatment.
7. To assess the safety of each treatment

Conditions and MedDRA coding

Adenomyosis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. [1] Premenopausal female, between 18 and 45 years of age inclusive, at the time of signing consent
2. [2] Patients with Adenomyosis - Associated Pelvic Pain (AAPP: i.e., any type of pelvic pain associated with adenomyosis: non-menstrual pelvic pain, dysmenorrhea and/or dyspareunia) as measured by Visual Analogue Scale (VAS) ≥ 40 units (as defined in chapter 9.3.1) at least once during screening period
3. [3] Patients with a history of AAPP for at least the past 6 months prior to the initial screening period
4. [4] Adenomyosis diagnosed by MRI or transvaginal ultrasound, or by means of hysteroscopy in the past 5 years
5. [5] Patients with one or more distinctive adenomyotic lesions, confirmed by transvaginal ultrasonography (TVUS) at screening
6. [6] Presence of one or more lesions suitable for treatment with Convulex, with the total dose not exceeding 40 mg (equivalent to 8 mL of the final solution at 5 mg/mL concentration), as identified under ultrasound guidance
7. [7] Patients with history of infertility and/or more than one spontaneous abortion
8. [8] Patients seeking to achieve pregnancy either through in-vitro fertilization (IVF) (optional) or spontaneous conception after the end of treatment with study medication and the wash-out period
9. [9] Patients with a history of regular menstrual cycles (21-35 days) while not being on any pharmacological treatment that could alter the menstrual cycle (e.g. oral contraceptive pills)
10. [10] Patients who agree to use only ibuprofen 400 mg as rescue medication up to a total daily dose of not more than 2400 mg
11. [11] Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study as evidenced by providing signed written informed consent according to chapter 5.3 of clinical trial protocol
12. [12] Patient agrees to sexual abstinence during the entire duration of the screening, treatment and for the wash-out period of the study. Does not apply if the patient can confirm either of the following: • surgical sterilization or bilateral tubal occlusion.

Exclusion criteria 29

1. [1] History of hypersensitivity or intolerance to the active substance or any of the excipients of the study and rescue medication
2. [2] Presence of an intrauterine device (IUD); participants with IUDs must have them removed prior to enrollment
3. [3] Positive suicidal ideation at screening or Day 0
4. [4] Known contraindications to the use of valproic acid (VPA), as specified in the SmPC, including epilepsy, systemic lupus erythematosus (SLE), hereditary enzyme deficiencies affecting the urea cycle, impaired kidney function, uncorrected systemic primary carnitine deficiency, or mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase γ (POLG), such as Alpers-Huttenlocher Syndrome
5. [5] Subject is pregnant or breast-feeding or is planning a pregnancy within the duration of the screening, treatment, and wash-out periods of the study or is less than 6 months postpartum or post-lactation or less than 1-month post-abortion, at the time of entry into the screening period
6. [6] Previous or concomitant use of hormonal agents before the screening period: ≤ 24 weeks for GnRH agonists and hormonal implants (or longer, depending on the specific implant type); ≤ 12 weeks for depot progestogens and danazol; ≤ 6 weeks for oral and vaginal contraceptives
7. [7] Patients with history of any type of cancer (including breast cancer)
8. [8] Other clinically significant gynaecological condition already known or identified during the screening period such as symptomatic uterine fibroids requiring treatment
9. [9] Presence of ovarian cyst of unknown etiology
10. [10] Visible myomas > 3 cm on ultrasound/MRI
11. [11] Cervical smear with pathological findings: class III or higher according to Papanicolaou, class IIp or higher according to the Munich III nomenclature or ASC-US or higher according to the Bethesda system
12. [12] Surgical treatment of adenomyosis within 3 months prior to the screening period
13. [13] Presence of chronic pelvic pain other than pain due to adenomyosis
14. [14] Acute or chronic hepatitis
15. [15] Hepatic insufficiency
16. [16] Family history of severe hepatitis, especially drug related
17. [17] Known hepatic porphyria
18. [18] Abnormal clinical and/or laboratory findings considered by the investigator as clinically relevant
19. [19] Positive results for HBs-Ag, anti-HCV and HIV-1/HIV-2-antibodies
20. [20] The use of antipsychotics or analgesics other than ibuprofen—including opioids, NSAIDs, paracetamol, or metamizole—is prohibited during the screening period. Short-term use (up to 3 days) of NSAIDs (other than ibuprofen) or metamizole is allowed for acute conditions (e.g., flu-like symptoms, emergency dental procedures or other acute conditions). The use of Fentanyl, Propofol, and Metoclopramide is also permitted only as short-term venous anaesthesia for the intralesional application of the study drug
21. [21] History of illicit drug or alcohol abuse within 6 months prior to screening visit
22. [22] Participation in another trial within 3 months before the screening period
23. [23] Previous enrolment in this study
24. [24] Any condition that, in the judgment of the investigator, may interfere with adherence to study procedures or study assessments
25. [25] Unreliability or lack of cooperation during the screening period
26. [26] Unwillingness or inability to complete the (paper) DIARY properly during the screening period
27. [27] Relatives and dependents of the PI/Sponsor; study site employees directly subordinate to the PI or sub-investigators
28. [28] Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study
29. [29] Patients who are known or suspected to be in custody or submitted to an institution due to a judicial order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Pre−post absolute change between baseline and final value after 29 days treatment in AAPP
2. Final value at the end of 29 days of treatment in the amount of analgesic rescue medication taken (ibuprofen 400 mg tablets)

Secondary endpoints 5

1. Pre−post absolute change of each pain type associated with adenomyosis (non-menstrual pelvic pain, dysmenorrhea, dyspareunia) as documented on a VAS (in units) at each visit
2. Clinical Global Impressions (CGI) scale after EoT on Day 30 (+4 days) visit)
3. Patient Global Impression of Change (PGIC) scale after EoT on Day 30 (+4 days) visit)
4. Pre−post absolute change in the lesion(s) size after EoT on Day 30 (+4 days) visit)
5. Pregnancy rate after the first in vitro fertilization cycle performed after a wash-out period of at least 30 days after the end of treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCDRD Cooperative Clinical Drug Research and Development AG

Sponsor organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Address

Dahlwitz, Lindenallee 70, Dahlwitz-Hoppegarten Lindenallee 70 Dahlwitz-Hoppegarten

City

Hoppegarten

Postcode

15366

Country

Germany

Scientific contact point

Organisation

Nadezhda Reproductive Science OOD

Contact name

Dr. Georgi Stamenov, Principal lnvestigator, Managing Director

Public contact point

Organisation

Nadezhda Reproductive Science OOD

Contact name

Spas Petkov, Managing Director

Third parties 2

Nadezhda Reproductive Science OOD

Sponsor organisation

Nadezhda Reproductive Science OOD

Address

Blaga Vest Str. 3

City

Sofia

Postcode

1330

Country

Bulgaria

Scientific contact point

Organisation

Nadezhda Reproductive Science OOD

Contact name

Dr. Georgi Stamenov, Managing Director, Principal Investigator

Public contact point

Organisation

Nadezhda Reproductive Science OOD

Contact name

Spas Petkov, Managing Director

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications