The AGAINST-PLD Study; An investigator-driven, randomized, open label clinical trial assessing efficacy of leuprorelin to halt disease progression in PLD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

completed 30 Apr 2025

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AbbVie

External identifiers

EU CT number

2023-506637-30-00

EudraCT number

2020-005949-16

WHO UTN

U1111-1278-8976

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine whether lowering estrogen and progesterone levels with the GnRH agonist leuprorelin decreases liver growth rates (in percent per year) in pre-menopausal women with severe polycystic liver disease during 18 months of treatment, comparing the direct start group (treated) and delayed start group (untreated).

Secondary objectives 4

1. Polycystic liver disease related complaints, as assessed by the change in scores on the validated polycystic liver disease questionnaire (PLD-Q) during the first 18 months of the trial, compared between the direct and delayed treatment arm
2. Change in liver growth rates within individuals before and during treatment; a paired analysis of liver growth rates within patients before start of treatment and during 18 months of treatment
3. Assess the tolerability and safety of leuprorelin in this specific patient group
4. Assess the quality of life, symptoms of depression and menopause related complaints

Conditions and MedDRA coding

polycystic liver disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Female patients
2. Age between 18 to 45 (inclusive) years
3. Very large liver for age, defined as the upper 10% of liver volumes in specific age categories (based on a retrospective polycystic liver disease registry, n=1.600 patients) o 18-30 yr; height adjusted TLV > 2.0 L/m o 30-35 yr; height adjusted TLV > 2.2 L/m o 35-40 yr; height adjusted TLV > 2.5 L/m o 40-45 years; height adjusted TLV > 3.0 L/m OR Age independent hTLV > 2.0 L/m and PLD-Q score >30.
4. With regard to the use of somatostatin analogues: o patients use a somatostatin analogue and still have confirmed liver growth; OR o patient have a reason not to use this medication, .e.g. patient used a somatostatin analogue in the past but had to stop due to inefficacy or because he/she did not tolerate it, patient has a contra-indication for using somatostatin analogues, patient or treating physician chose not to try somatostatin analogues, no availability of somatostatin analogues
5. Voluntary written informed consent before performance of any study-related procedures not part of standard medical care, and able to read, comprehend, and respond to study questionnaires.
6. Diagnosis of polycystic liver disease defined as the presence of more than 10 liver cysts

Exclusion criteria 11

1. Post-menopausal status or (vasomotor) symptoms indicating upcoming menopause
2. Anti Mullerian Hormone (AMH) measurement at screening visit <0.03 ng/ml.
3. Active desire to have children, pregnancy or breast-feeding
4. Contra-indications for leuprorelin, such as history of cardiovascular disease, history of osteoporosis or osteoporosis determined by DEXA-scan at screening (T score ≤ -2.5), unexplained vaginal bleeding, or a known intolerance for leuprorelin
5. Liver transplantation or liver surgery expected within 1.5 years, to the discretion of the study doctor
6. Use of hormonal oral contra-conception containing estrogen and/or progesterone. In contrast, a hormone containing uterine device is not an exclusion criteria.
7. Contra-indications for both MRI and CT assessments (such as implants) or not able or willing to undergo MRI and CT scan for other reasons (e.g. claustrophobia, profound obesity)
8. Kidney transplantation or chronic use of immunosuppressive agents (such as cyclosporine, mycophenolic acid, tacrolimus but not prednisolone) for other indications
9. Therapy resistant severe hypertension, defined as a systolic blood pressure >160 mmHg and/or diastolic blood pressure > 100 mm Hg.
10. Clinically significant, uncontrolled medical condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which would affect the efficacy of safety analysis if the condition exacerbated during the study, or that may significantly interfere with study compliance, such as, but not restricted to, recurrent cholangitis, recurrent ascites or hepato-venous outflow obstruction, (history of) depression
11. Participation in other interventional studies at the same time.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome variable is liver growth rate (in % per year), calculated over the first 18 months of the trial (screening-18 months) based on liver volumes measured on MRI, comparing the direct start group and delayed start group.

Secondary endpoints 3

1. Polycystic liver disease related complaints, using the validated PLD Questionnaire. The change in the score on the PLD Questionnaire will be compared between patients in the direct start group and the delayed start group after 18 months of treatment.
2. Liver growth rate (in % per year) compared within individuals before start of treatment and during treatment.
3. (Severe) Adverse events

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

R.T. Gansevoort

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

R.T. Gansevoort

Locations

1 EU/EEA country · 2 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 10 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