Efficacy and safety of Silycus® in Cushing’s disease: a multicenter, single arm, open label, dose titration, proof of concept study (Silycus®-21)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

17 Nov 2025 → ongoing

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-518869-99-00

EudraCT number

2020-005605-93

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluate the efficacy of Silycus® to decrease and/or normalize excess cortisol secretion in patients with active Cushing’s disease, assessed by either 24 hour urinary free cortisol, midnight salivary cortisol or suppression by low dose dexamethasone.

Secondary objectives 3

1. Evaluate the effect of Silycus® on signs and symptoms of hypercortisolism
2. Assess the safety and tolerability of Silycus® in patients with Cushing’s disease
3. Evaluate the PK profile of silibinin in patients with Cushing’s disease

Conditions and MedDRA coding

Cushing's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Adult, i.e., age >= 18 years, female and male patients with active Cushing’s disease. Cushing’s disease will be diagnosed according to established guidelines. Patients will be either de novo diagnoses or persistent/recurrent disease Medical records will be collected and used to support the diagnosis.
2. Mean value of 24-hour urinary free cortisol (UFC) in at least three collections 1.5 times above the upper limit of normal range (ULN) and elevated late night salivary cortisol (at least 2 measurements > ULN) or unsuppressed cortisol after 1 mg dexamethasone (i.e., serum cortisol at 8 AM >1.8 micrograms/deciliter)
3. Patients on inadequate or not tolerated medical treatments for Cushing’s disease amenable to minimum drug wash-out period
4. Patients with de novo Cushing’s disease if not surgical candidates or if surgery is delayed beyond the projected duration of the present study
5. Patients willing to provide written informed consent to participate in the study and adhere to protocol requirements

Exclusion criteria 11

1. Patients who do not fulfil criteria for active Cushing’s disease
2. Patients submitted to pituitary radiosurgery/radiotherapy within the past 3 years
3. Patients with de novo Cushing’s disease who are amenable to surgery which is available within the projected duration of the present study
4. Patients for whom the managing physician considers interruption of ongoing medical treatment for Cushing’s disease to be inappropriate
5. Pregnant and/or lactating women or women unwilling to use contraceptive medication and contraceptive devices starting from one month before Silycus® administration and for up to two months after silibinin withdrawal
6. Patients with active, severe kidney or liver disease
7. Patients with history of alcohol or drug abuse in the last 6 months
8. Patients with known hypersensitivity to components of Silycus®
9. Patients on mitotane will not be enrolled as a drug washout of at least 6 months is deemed unethical
10. Patients who are unwilling to perform study-related procedures
11. Any other criteria that may preclude patient participation according to investigator judgement.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Efficacy of silibinin will be assessed on UFC, late night salivary cortisol levels and suppression with low dose dexamethasone.
2. The composite endpoint comprises: the percentage of patients in whom UFC normalized or decreased by at least 50% compared to pretreatment values, the percentage of patients with elevated late night salivary cortisol at baseline in whom salivary cortisol normalized and percentage of patients who failed to suppress after low dose dexamethasone at baseline in whom normal suppression was restored. Efficacy will be assessed after 12 weeks of administration.

Secondary endpoints 3

1. Establish the effect of Silycus® on clinical signs and symptoms of Cushing’s disease. These effects, i.e. changes in body weight, blood pressure, glucose control, electrolyte derangements, leukocytosis, will be assessed after 12 weeks administration
2. Analysis of safety of Silycus® administration based on frequency and severity of adverse events
3. Evaluation of the PK profile of silibinin in patients with Cushing’s disease (after the first dose, uptitration and at steady state)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Sponsor organisation

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Address

Via Fossignano 2

City

Aprilia

Postcode

04011

Country

Italy

Scientific contact point

Organisation

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Contact name

Paola Accossato

Public contact point

Organisation

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Contact name

Paola Accossato

Third parties 4

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 27 files

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

Application history

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