E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uterine myomas are benign, monoclonal, hormone sensitive, smooth muscle tumors of the uterus. It is the most common tumor of the female reproductive tract in pre-menopausal women and mostly asymptomatic. When symptomatic, its cardinal symptoms are heavy uterine bleeding, anaemia, abdominal pressure, abdominal pain, urinary frequency and infertility. Myomas affect approximately 40% of women between 35 and 55 years. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046801 |
E.1.2 | Term | Uterine myoma |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy: Primary objective of this study is to demonstrate non inferior efficacy of PGL4001 versus GnRH-agonist to reduce, prior to surgery, excessive uterine bleeding caused by uterine myomas. Safety: Primary safety objective is to demonstrate superior safety and tolerance of PGL4001 versus Gonadotropin Releasing Hormone agonist (GnRH-agonist) regarding castration-related symptoms and their consequences which principal parameters are serum oestradiol levels and hot flushes. |
|
E.2.2 | Secondary objectives of the trial |
Efficacy: Secondary objectives are to demonstrate improvement in myoma-related symptoms such as pain and to assess PGL4001 capacity to decrease uterine volume as well as volume of the three largest myomas. Safety: Secondary safety objective is to assess overall safety of PGL4001 in subjects with uterine myomas. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for inclusion into this study, the subjects must fulfil all of the following criteria: 1. The subject must provide written informed consent prior to any study related procedures. 2. The subject must be a pre-menopausal woman between 18 and 50 years inclusive. 3. The subject must have a PBAC score >100 during day 1 to day 8 of menstruation preceding the baseline visit. 4. The subject must have a myomatous uterus ≤ 16 weeks. 5. The subject must have at least one uterine myoma of ≥ 3 cm diameter in size and no myoma larger than 10 cm diameter in size diagnosed by ultrasound. 6. The subject must be eligible for one of these surgical procedures: i.e. hysterectomy, myomectomy, uterine artery embolization or endometrial ablation within 13 weeks and up to 14 weeks from baseline study visit. 7. The subject must have a clinical breast examination without significant findings at the screening visit. 8. The subject must have no clinically significant findings at PAP smear, performed within the past 12 months or at the screening visit. 9. If of childbearing potential the subject must be practicing a non-hormonal method of contraception as listed below: - Sexual abstinence - Diaphragms - Condom or partner with a vasectomy performed at least 6 months prior to the study and confirmed azoospermia. 10. If of non childbearing potential, the subject must have had a tubal ligation sterilisation at least two months before study start. 11. The subject must have a BMI ≥ 18 and ≤ 40.
|
|
E.4 | Principal exclusion criteria |
To be eligible for inclusion in this study the subjects must not meet any of the following criteria: 1.The subject has a history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization. 2.The subject has a history of or current uterine, cervical, ovarian or breast cancer. 3. The subject has: - a history of atypical hyperplasia - or a current endometrium hyperplasia (atypical or non atypical) in the screening biopsy or in a biopsy performed within the past 6 months. 4.The subject has a condition requiring immediate blood transfusion or a level of Hb ≤ 6 g/dL. 5.The subject has a known hemoglobinopathy (i.e. Sickel Cell anaemia and Thalassamia). 6.The subject has a known severe coagulation disorder. 7.The subject has a large uterine polyp (> 2cm). 8.The subject has one or more ovarian cysts ≥ 4cm in diameter diagnosed by US. 9.The subject has a history of or current treatment for myoma with a SPRM or a GnRH-agonist. 10.The subject has been taking: a.Treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive: within the month before the screening visit. b.Acetylsalicylic acid , mefenamic acid, anticoagulants such as cumarins and/or antifibrinolytic drugs such as tranexamic acid: within one week before the screening visit, c.Systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months before the screening visit, respectively. 11.The subject is likely to require treatment during the study with drugs that are not permitted by the study protocol: progestins (systemic or progestin releasing intra-uterine system), oral contraceptives, systemic glucocorticoids (oral and injectable), acetylsalicylic acid, mefenamic acid, anticoagulants such as cumarins and/or antifibrynolytic drugs such as tranexamic acid. 12.The subject has a history of or known current osteoporosis. 13.The subject has abnormal hepatic function at study entry (defined as AST, ALT, γGT, alkaline phosphatase or total bilirubin above 2 ULN). 14.The subject has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study. 15.The subject has a current (within twelve months) problem with alcohol or drug abuse. 16.The subject has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. 17.The subject has abnormal baseline findings, any other medical condition(s) or psychiatric condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject’s safety or interfere with study evaluations. This does include the use of agents known to induce or inhibit the hepatic cytochrome CYP3A4. 18.The subject has an allergy to GnRH agonist, SPRMs or progestins or any of the ingredients of the study drug tablet (see list of ingredients in the investigator’s brochure), 19.The subject is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: Percentage of subjects with reduction of uterine bleeding at Week 13 visit defined as PBAC score < 75 at end-of-treatment visit (Week 13 visit). PBAC is one of the current standard methods used to objectively estimate menstrual blood loss and diagnose menorrhagia. The method which was developed and validated by Higham and Janssen defines excessive bleeding as a PBAC score >100. Primary safety endpoint: - Mean serum E2 levels at end of treatment visit (Week 13 visit) for PGL4001 compared with GnRH-agonist. - Percentage of subjects reporting moderate or severe hot flushes as adverse events throughout the treatment period for PGL4001 compared with GnRH-agonist.
|
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |