A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD

Study Overview
=================
Brief Summary
-----------------
The purpose of the trial is to compare the effectiveness and safety of 2 treatment regimens of CAM2029 (given weekly or every 2 weeks) to placebo in participants with symptomatic PLD, either isolated as in autosomal dominant PLD (ADPLD) or associated with autosomal dominant polycystic kidney disease (ADPKD). In the Treatment Period of the trial, participants will be allocated at random to 1 of the 3 treatment arms in a 1:1:1 ratio. After completing the Treatment Period (53 weeks) participants may proceed to a 24-week open-label extension part of the trial and then only receive the same CAM2029 treatment. The active ingredient in CAM2029, octreotide, is administered as a subcutaneous depot using Camurus' FluidCrystal® technology.

Official Title
-----------------
A Randomized, Placebo-controlled, Double-blind, Multi-center Trial to Assess Efficacy and Safety of Octreotide Subcutaneous Depot (CAM2029) in Patients With Symptomatic Polycystic Liver Disease

Conditions
-----------------
Polycystic Liver Disease

Intervention / Treatment
-----------------
* Drug: CAM2029
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patient, ≥18 years at screening Diagnosis of PLD (associated with ADPKD or isolated as in ADPLD) as defined by htTLV ≥1800 mL/m at screening Presence of at least 1 of the following PLD-related symptoms within 2 weeks before screening: bloating, fullness in abdomen, lack of appetite, feeling full quickly after beginning to eat, acid reflux, nausea, rib cage pain or pressure, pain in side, abdominal pain, back pain, shortness of breath after physical exertion, limited in mobility, concern about abdomen getting larger, dissatisfied by the size of abdomen Not a candidate for, or not willing to undergo, surgical intervention for hepatic cysts during the trial Exclusion Criteria: Surgical intervention for PLD within 3 months before screening Treatment with a somatostatin analogue (SSA) within 3 months before screening Non-responsive to previous treatment of PLD with an SSA as per the Investigator's assessment Systematic cholelithiasis within 3 months before screening or previous medical history of cholelithiasis induced by SSAs unless treated with cholecystectomy Presence of extrahepatic cysts that, in the Investigator's opinion, may prevent the patient from safely participating in the trial Severe kidney disease, as defined by eGFR <30 mL/min/1.73^m2 Severe liver disease defined as liver cirrhosis of Child-Pugh class C Any other current or prior medical condition that may interfere with the conduct of the trial or the evaluation of its results in the opinion of the Investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAM2029 once weekly<br>0.5 mL CAM2029 10 mg, subcutaneous (SC) injection, once weekly | Drug: CAM2029<br>* SC injection using a pre-filled pen<br>* Other names: octreotide subcutaneous depot;|
| Experimental: CAM2029 once every 2 weeks<br>0.5 mL CAM2029 10 mg, SC injection, every 2 weeks and 0.5 mL placebo, SC injection, once every 2 weeks (alternating with CAM2029 dosing) | Drug: CAM2029<br>* SC injection using a pre-filled pen<br>* Other names: octreotide subcutaneous depot;Drug: Placebo<br>* SC injection using a pre-filled pen<br>|
| Placebo Comparator: Placebo<br>0.5 mL placebo, SC injection, once weekly | Drug: Placebo<br>* SC injection using a pre-filled pen<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height-adjusted total liver volume (htTLV) | Change from baseline to Week 53 in htTLV as determined by MRI volumetry | From screening until treatment week 53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PLD symptom (PLD-S) score | Key secondary endpoint. Change from baseline to Week 53 in the PLD-S measure score | From screening to week 53 | 
| htTLV | Change from baseline in htTLV as determined by MRI volumetry | From screening until treatment weeks 13, 25 and 77 | 
| PLD-S | Change from baseline in the PLD-S measure score | From screening to weeks 13, 21, 25, 39 and 77 | 
| Height-adjusted total kidney volume (htTKV) | Change from baseline in htTKV as determined by MRI volumetry | From screening until treatment weeks 13, 25, 53 and 77 | 
| Estimated glomerular filtration rate (eGFR) | Change from baseline in eGFR, assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation using serum concentrations of creatinine and cystatin C | From treatment week 1 to weeks 13, 25, 53, 65 and 77 | 
| PLD impact (PLD-I) score | Change from baseline in the PLD-I measure score | From screening to weeks 13, 21, 25, 39, 53 and 77 | 
| Clinical Global Impression of Severity (CGI-S) score | Change from baseline in the CGI-S score | From treatment week 1 to weeks 13, 21, 25, 53 and 77 | 
| Patient Global Impression of Severity (PGI-S) score | Change from baseline in the PGI-S score | From screening to weeks 13, 21, 25, 39, 53 and 77 | 
| Patient Global Impression of Change (PGI-C) score | Change from baseline in the PGI-C score | At treatment weeks 13, 21, 25, 39, 53 and 77 | 
| Short Form-36 (SF-36) score | Change from baseline in the SF-36 score | From treatment week 1 to weeks 25, 53 and 77 | 
| Polycystic Liver Disease Questionnaire (PLD-Q) | Change from baseline in the PLD-Q score | From treatment week 1 to weeks 25, 53 and 77 | 
| Adverse events (AEs) | Incidence of AEs | From screening to the safety follow-up, assessed up to approximately 21 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polycystic liver, PLD, ADPLD, ADPKD, PCLD, height-adjusted total liver volume, htTLV, CAM2029, POSITANO