To demonstrate that Nanocort is safe and effectively reduces the inflammatory signs and symptoms of active GO.
ID
Source
Brief title
Condition
- Eye disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Number of patients with a predefined response to treatment.
Secondary outcome
See protocol.
Background summary
The mainstay of treatment for patients with moderate to severe Graves*
Orbitopathy (GO) currently consists of various dose schemes of intravenous (IV)
methylprednisolone or high doses oral prednisone. To avoid the frequent and
potentially serious adverse effects of such treatment, new immunomodulating
therapies are required. In a small study, IV administration of long-circulating
liposomal prednisolone (Nanocort, LCLP) has been shown effective in rheumatoid
arthritis without causing the typical glucocorticoid-related adverse events
(AEs). It is hypothesized that GO can also be effectively treated with LCLP and
that the number of AEs will be reduced.
Study objective
To demonstrate that Nanocort is safe and effectively reduces the inflammatory
signs and symptoms of active GO.
Study design
Open label, multicentre, dose-escalating study (phase I/II).
Intervention
The first 10 subjects in this trial will be treated with 150 mg/infusion of
Nanocort administered IV at week 0 and 2. Infusion will take approximately 2.5
hours. If three or more of these patients respond to treatment, another cohort
of 10 subjects will be treated with 150 mg/infusion of Nanocort administered IV
at week 0, 2 and (if applicable) 4.
Study burden and risks
The incidence of infusion reactions to liposomes (empty placebo as well as
drug-loaded) is not unlike that for other colloidal formulations and biologics:
5-10%. AEs (possibly) associated with Nanocort appear to be manageable.
Compared to conventional therapy, the study regimen (i.e. treatment and control
visits together) involves reduced burden (12 hospital visits versus 8) and
reduced steroid dose (total 4500/7500 mg methylprednisolone versus 300/450 mg
Nanocort). In consequence of the lower steroid dose, it has to be expected that
the incidence of AEs which are associated with sytemic steroid exposure will be
less.
Schiedamse Vest 180
Rotterdam 3011 BH
NL
Schiedamse Vest 180
Rotterdam 3011 BH
NL
Listed location countries
Age
Inclusion criteria
1. Male or female * 18 years old.
2. Informed consent.
3. Patients are able and willing to complete the study (12 months follow-up).
4. Active GO, defined as Clinical Activity Score (CAS) * 3.
5. Moderate to severe GO (Bartalena et al. 2016):
6. Euthyroidism for at least 3 months with antithyroid drugs or following thyroidectomy, or 6 months following radioiodine administration.
Exclusion criteria
1. Sight threatening GO due to optic neuropathy (decrease of (pinhole) vision, visual field loss, prolonged VEP, diminished colour vision) or severe keratopathy.
2. Any concurrent illness, disability or clinically significant abnormality that may, as judged by the investigator, affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol.
3. Current participation in another interventional clinical trial (with subjects having
received an investigational drug within 30 days prior to the baseline visit).
4. Treatment with oral, rectal or injectable (including intra-articular) glucocorticoids within 6 weeks prior to baseline visit. Inhaled glucocorticoids are allowed. Topical steroids are allowed, however subjects should not have received more than 100 gram of a mild to moderate topical corticosteroid cream per week, 50 gram of a potent corticosteroid cream per week or 30 gram of a very potent topical corticosteroid cream per week in the 4 weeks prior to the baseline visit.
5. Patients who are unlikely to adequately comply with the trial*s procedures (due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or noncompliance).
6. Women who are lactating, pregnant (positive pregnancy test at screening) or planning to become pregnant during the course of the study.
7. Unwillingness to use reliable and acceptable contraceptive methods untill 3 months after last study medication except for female patients who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or at least 1 year postmenopausal
8. Uncontrolled Diabetes Mellitus.
9. History of a psychiatric disease (psychosis, depression, mania).
10. History of or active hepatitis or Human immunodeficiency virus.
11. Abnormal hepatic function (ALT/AST or bilirubin > 2 x upper limit of normal) at screening.
12. Abnormal renal function (Blood Urea Nitrogen or creatinine >1.25 x upper limit of normal) at screening.
13. Signs of active infection, requiring systemic treatment.
14. Major surgery within the 60 Days prior to screening or planned surgery during study period.
15. Malignant disease, unless cured.
16. Clinically significant out-of-range values on hematology panel, at discretion of the PI.
17. Poor peripheral venous access (as per Investigator or site personnel opinion).
18. Current substance abuse or alcohol abuse.
19. Contraindications for MRI.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001158-33-NL |
| CCMO | NL61298.078.17 |
| OMON | NL-OMON24926 |