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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Polycystic Liver Disease
• Intervention / Treatment: Drug: CAM2029; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Camurus AB; Phone Number: +46 46 286 57 30; Email: medicalinfo@camurus.com

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • University Hospitals KU Leuven
• Germany
  • Hannover, Germany, 30625
    • Hannover Medical School
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboud UMC, Department of Gastroenterology and Hepatology
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10065
      • The New York Presbyterian Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75380
      • University of Texas Southwestern Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23602
      • Bon Secours Richmond Community Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAM2029 once weekly; 0.5 mL CAM2029 10 mg, subcutaneous (SC) injection, once weekly	Drug: CAM2029; SC injection using a pre-filled pen; Other Names: octreotide subcutaneous depot
Experimental: CAM2029 once every 2 weeks; 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; SC injection using a pre-filled pen; Other Names: octreotide subcutaneous depot; Drug: Placebo; SC injection using a pre-filled pen
Placebo Comparator: Placebo; 0.5 mL placebo, SC injection, once weekly	Drug: Placebo; SC injection using a pre-filled pen

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

Collaborators and Investigators

• Sponsor: Camurus AB
• Investigators: Principal Investigator: Joost Drenth, MD, Department of Gastroenterology and Hepatology, Radboud UMC Nijmegen, The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ADPKD; CAM2029; PLD; Polycystic liver; ADPLD; PCLD; height-adjusted total liver volume; htTLV; POSITANO
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Pathological Conditions, Anatomical; Liver Diseases; Cysts; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: HS-20-677; 2021-003764-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No