Polycystic Liver Disease
Conditions
Keywords
Polycystic liver, PLD, ADPLD, ADPKD, PCLD, height-adjusted total liver volume, htTLV, CAM2029, POSITANO
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 120-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.
Interventions
DRUGCAM2029
SC injection using a pre-filled pen
DRUGPlacebo
SC injection using a pre-filled pen
Sponsors
Camurus AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height-adjusted Total Liver Volume (htTLV) | From screening until treatment week 53 | Magnetic resonance imaging (MRI) was used to measure the total liver volume (TLV) at baseline and at Week 53 and was adjusted to the participant's height. The change from baseline to Week 53 was calculated as the difference between htTLV values at Week 53 and baseline. The difference in treatment effect between the groups was presented as a ratio expressed in percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PLD Symptom (PLD-S) Score | From screening to Week 53 | Change from baseline to Week 53 in the PLD-S measure score. |
| htTLV | From screening until treatment weeks 13, 25, 77, 125 and 173 | Change from baseline in htTLV as determined by MRI volumetry |
| PLD-S | From screening to weeks 13, 21, 25, 39, 77, 101, 125, 149 and 173 | Change from baseline in the PLD-S measure score |
| Height-adjusted Total Kidney Volume (htTKV) | From screening until treatment weeks 13, 25, 53, 77, 125 and 173 | Change from baseline in htTKV as determined by MRI volumetry |
| Total Liver Cyst Volume | From screening to treatment weeks 13, 25, 53, 77, 125 and 173 | Change from baseline in total liver cyst volume determined by MRI volumetry |
| Estimated Glomerular Filtration Rate (eGFR) | From treatment week 1 to weeks 13, 25, 53, 65, 77, 101, 125, 149 and 173 | 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 |
| PLD Impact (PLD-I) Score | From screening to weeks 13, 21, 25, 39, 53, 77, 101, 125, 149 and 173 | Change from baseline in the PLD-I measure score |
| Clinical Global Impression of Severity (CGI-S) Score | From treatment week 1 to weeks 13, 21, 25, 53, 77, 101, 125, 149 and 173 | Change from baseline in the CGI-S score |
| Patient Global Impression of Severity (PGI-S) Score | From screening to weeks 13, 21, 25, 39, 53, 77, 101, 125, 149 and 173 | Change from baseline in the PGI-S score |
| Patient Global Impression of Change (PGI-C) Score | At treatment weeks 13, 21, 25, 39, 53, 77, 101, 125, 149 and 173 | Change from baseline in the PGI-C score |
| Short Form-36 (SF-36) Score | From treatment week 1 to weeks 25, 53, 77, 101, 125, 149 and 173 | Change from baseline in the SF-36 score |
| Polycystic Liver Disease Questionnaire (PLD-Q) | From treatment week 1 to weeks 25, 53, 77, 101, 125, 149 and 173 | Change from baseline in the PLD-Q score |
| Adverse Events (AEs) | From screening to the safety follow-up, assessed up to approximately 47 months. | Incidence of AEs |
Countries
Belgium, Germany, Netherlands, United States
Contacts
PRINCIPAL_INVESTIGATORJoost Drenth, MD
Department of Gastroenterology and Hepatology, Radboud UMC Nijmegen, The Netherlands
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 7.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Height-adjusted total liver volume (htTLV) | 3751.61 mL/m STANDARD_DEVIATION 2157.086 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 1 / 23 | 0 / 23 |
| other Total, other adverse events | 24 / 24 | 21 / 23 | 22 / 23 |
| serious Total, serious adverse events | 2 / 24 | 3 / 23 | 5 / 23 |
Outcome results
None listed