Estetrol Therapy in Sjogren's Syndrome: An Open Proof of Concept Study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-003537-16-NL
• Date of registration: 09/08/2007
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC
• Public title: Estetrol Therapy in Sjogren's Syndrome: An Open Proof of Concept Study
• Scientific title: Estetrol Therapy in Sjogren's Syndrome: An Open Proof of Concept Study
• Date of first enrolment: 04/09/2008
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003537-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
- Fulfill American -European consensus criteria for primary Sjogren's syndrome
- Post-menopausal women older than 18 and younger than 70
- Body mass index =18 and =32 kg/m2
- Complaints consistent with oral and ocular dryness
- SSA and/or SSB positive
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
2) Have a history of malignancy
3) Have a history of trombo-embolic events or a positive lupus anticoagulant
4) Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
5) Clinically significant abnormal results of routine hematology, serum biochemistry, urinanalysis, in the opinion of the Investigator at screening, and/or known ECG abnormalities .
6) Known clinically significant abnormal mammogram (presence of any non-cystic mass) within one year before study start.
7) Known clinically significant abnormalities of the uterus and/or ovaries detected earlier by examination and/or ultrasound (non-physiological ovarian mass or significant uterine pathology or an endometrium greater than 6 mm or the presence of cysts).
8) A cervical smear with clinically relevant abnormal cytology within one year before study start.
9) Previous use of estrogen/progestogen within:
- 6 months for depot preparations.
- 8 weeks for oral preparations or progestogen containing IUD.
- 4 weeks for transdermal preparations.
10) Use of hormone containing implant at any time.
11) Contraindications for using steroids:
- A history of, or existing thromboembolic, cardiovascular or cerebrovascular disorder.
- A history of, or existing conditions predisposing to, or being prodromi of, a thrombosis.
- A known defect in the blood coagulation system (e.g. deficiencies in AT-III, protein C, S, and APC resistance).
- A medical history positive for the presence of more than one risk factor for vascular disease (e.g. dyslipoproteinemia; diabetes mellitus; hyperhomocysteinemia; systemic lupus erythematosus; chronic inflammatory bowel disease; smoking; venous thromboembolism in sibling or parent below the age of 50, or arterial disease in sibling or parent below the age of 30-35).
- Hypertension, i.e. systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg.
- Disturbance of liver function: cholestatic jaundice, a history of jaundice of pregnancy or jaundice due to previous estrogen use. Known Rotor syndrome and Dubin-Johnson syndrome.
- Known or suspected estrogen-dependent tumors or endometrial hyperplasia.
- Undiagnosed vaginal bleeding.
- Known Porphyria.
- A history during pregnancy or previous estrogen use of severe pruritus, herpes gestationis or deterioration of otosclerosis.
12) Any enzyme affecting drugs from 30 days prior to Day 1 (see Appendix I) and the use of griseofulvin, phenytoin, barbiturates, carbamazepine, rimfampicin, nelfinavir, ritonavir, ketonazole, primidone, oxcarbazepine, topiramate, felbamate, herbal remedies containing hypericum perforatum (St. John’s wort).
15) Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
16) Use of any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Primary Sjogren's Syndrome
MedDRA version: 9.1 Level: LLT Classification code 10040767 Term: Sjogren's syndrome

Intervention(s)

Product Name: estetrol
Product Code: E4
Pharmaceutical Form: Oral solution

Primary Outcome(s)

Main Objective: To explore overall response to treatment with estetrol in patients with primary Sjögren’s syndrome.

Primary end point(s): Primary endpoint consists of a composite endpoint concerning meaningful improvement across 2 of 3 Sjögren’s syndrome disease domains: oral, ocular, and laboratory tests. Oral improvement will be defined as =20% in the patient’s assessment of dry eyes (on a 100 mm VAS) or =20% improvement in total unstimulated salivary flow. Ocular improvement will be difined as =20% improvement in either the patient’s assessment of dry eyes by VAS or the results of the Schirmer test without anaesthetic. Laboratory improvement will be defined as =20% improvement in the serum IgG or the ESR.

Secondary Objective: To assess:
• improvement in quantitative levels of SSA and/ or SSB
• decrease in pilocarpine use during treatment.
• improvement in results of the SF36
• safety of estetrol treatment

Secondary ID(s)

PR3084