A randomised, controlled clinical trial assessing the efficacy of;Lanreotide to halt disease progression in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by
progressive cyst formation in both kidneys, leading to end stage renal disease.
It is the most common hereditary disease, with a prevalence rate of 1 in 400 to
1 in 1,000 persons. The majority of patients also have progressive cyst
formation in the liver, leading to pain and discomfort. At present there is no
proven therapeutic intervention to slow down or halt disease progression in
human ADPKD. The development of renoprotective treatments that are well
tolerated, is therefore of major importance.

In this respect, somatostatin analogues are promising for especially polycystic
liver disease, but also for the renal phenotype. However, the studies that have
been performed thus far, were underpowered and of too short duration to reach a
definitive conclusion on the potential reno- and hepatoprotective efficacy of
somatostatin analogues. Therefore, the present study is designed as a
relatively large scale randomised clinical trial with sufficient duration of
follow-up to investigate whether the somatostatin analogue lanreotide slows
progression of polycystic kidney and liver disease in ADPKD-patients.

First, to demonstrate whether Lanreotide attenuates progression of the renal
phenotype in ADPKD patients as measured by change in rate of renal function
decline and change in renal volume. Second, to demonstrate whether Lanreotide
modifies progression of the liver phenotype in the subset of ADPKD patients
with moderate to severe polycystic liver disease as measured by change in liver
volume.

Multi-center, randomised, controlled, parallel arm investigator-driven trial to
investigate the effect of the long acting somatostatine analogue Lanreotide
versus standard care in subjects diagnosed with ADPKD based on the Ravine
criteria (with number of cysts known from a previous ultrasound or magnetic
resonance imaging [MRI]) The total study duration will be 34 months.

The patients will be divided into two groups. One group of patients will
receive in addition to standard care a dose of lanreotide 120 mg sc every 28
days for 30 months. When eGFR falls below 30 mL/min/1.73m2 or in case of dose
related side effects, down titration will take place. The other group of
patients will receive standard care, for 30 months.

When compared to routine clinical care the burden and risk associated with
participation are:
• In general ADPKD patients with more advanced renal disease visit an
out-patient department once every 3 months routinely. Therefore this study
imposes 4 extra visits to an outpatient department when compared to routine
care (screening, baseline, month 1 and 2)
• In general ADPKD patients with more advanced renal disease when visiting an
out-patient department collect 24hr urine and blood is drawn for routine
clinical chemistry. During the baseline visit and yearly teherafter extra blood
will be drawn for biobanking and at each visit to the out-patient department 1
extra EDTA plasma tube and 1 extra serum tube will collected and for post-study
central assessment of creatinine and cystatin C concentration.
• 3 times a MRI of liver and kidneys (without contrast)
• 7 times a questionnaire
• half of the patients will be exposed to the somatostatin analogue lanreotide.

The potential benefit for participating subjects are that lanreotide may slow
down the progression of ADPKD, thus ameliorating the rate of renal function
decline in these patients, thereby potentially postponing the need for renal
replacement therapy, and inducing less cyst growth, thereby potentially leading
to less complaints that are related to cyst size and abdominal distension (e.g.
abdominal pain, early satiety and dyspnoea).