E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Multiple fluid filled sac in liver |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the treatment effect of CAM2029 compared to placebo on liver volume in patients with polycystic liver disease (PLD)
|
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the treatment effect of CAM2029: o Compared to placebo on patient-reported PLD-related symptoms o On liver volume over time in patients with PLD o On patient-reported PLD-related symptoms over time o Over time on kidney volume in patients with presence of kidney cysts o Over time on renal function in patients with presence of kidney cysts o Over time on patient-reported PLD-related impact on functioning and well-being o Over time on PLD-related symptoms o Over time on functioning and well-being o Over time on PLD-related symptoms • To evaluate the safety and tolerability of CAM2029 • To assess the PK of octreotide after administration of CAM2029 Exploratory Objectives • To evaluate treatment effect of CAM2029 over time on o Total liver cyst volume o Change in liver volume compared to the pre-treatment growth rate o IGF-1 • Assess patients’ satisfaction with CAM2029 T/T & self- administration
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patient, ≥18 years at screening • Diagnosis of PLD (associated with ADPKD or isolated as in ADPLD) with 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
|
|
E.4 | Principal exclusion criteria |
• Surgical intervention for PLD within 3 months before screening. For sclerotherapy patients, at least 6 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 • Symptomatic 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 • Use of oral contraceptives or estrogen supplementation within 3 months before screening • Poorly controlled diabetes (hemoglobin A1c ≥10%) at screening • Patients with a known history of hypothyroidism, unless they have been on adequate and stable replacement thyroid hormone therapy for at least 3 months before the first dose of the IMP. • Uncontrolled hypertension defined by a systolic blood pressure of >160 mmHg and/or diastolic blood pressure of >100 mmHg at screening • History of significant cardiac disease or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the trial, such as uncontrolled or significant cardiac disease, including any of the following: a. History of myocardial infarction, angina pectoris or coronary artery bypass graft within 6 months before screening b. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block or high-grade atrioventricular block (e.g. bifascicular block, Mobitz type II and third-degree atrioventricular block) c. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i. Risk factors for Torsades de Pointes including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure or history of clinically significant/symptomatic bradycardia ii. Treatment with concomitant medication(s) with a "Known risk of Torsades de Pointes" that cannot be discontinued or replaced by safe alternative medication at least 5 half-lives or 7 days (whichever is longer) before the first dose of IMP iii. Patients with a baseline QTc interval corrected by Fridericia's formula >450 msec for males and >470 msec for females at screening • Patients with vascular compromise, including, but not limited to, mesenteric thrombosis, portal hypertension and thrombocytopenia (platelet counts less than 100x109/L) • Pregnant, lactating or planning to be pregnant during the trial • History of solid organ transplantation. Exception for kidney transplant patients • Contraindications to, or interference with, MRI assessments, as dictated by local hospital regulations
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 53 in height-adjusted total liver volume (htTLV) as determined by magnetic resonance imaging (MRI) volumetry
• Change from baseline in total liver cyst volume determined by MRI volumetry • Rate of change in htTLV (calculated from up to the last 5 years prior to trial entry) as compared to htTLV change from baseline • Change from baseline in serum Insulin-like growth factor-1 (IGF-1) levels • Treatment Satisfaction Questionnaire for Medication (TSQM) scores using all 4 domains of TSQM v1.4 (effectiveness, side effects, convenience and satisfaction) • Change from PRE module to the POST module in Self-Injection Assessment Questionnaire (SIAQ) scores • Data collected in the pre-defined Validation Battery to be used for psychometric analyses to confirm measurement properties, reliability, validity and interpretability • Qualitative analysis of patients’ entry and exit interviews • Semi-quantitative analysis of anti-octreotide antibodies
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints: Before trail period 1. During Screening period (Week -12 to -1) During trial phase 2. Week 1 3. Week 13 4. Week 21 5. Week 25 6. Week 39 7. Week 53 8. Week 77
If the MRI of the liver and kidneys performed at screening and Week 77/End-of-Treatment include satisfactory images of the gallbladder, these scans may also be used for the safety assessment by the Investigator. |
|
E.5.2 | Secondary end point(s) |
• Change from baseline to Week 25 in the Polycystic Liver Disease Symptoms (PLD-S) measure score • Change from baseline in htTLV as determined by MRI volumetry • Change from baseline in the PLD-S measure score • Change from baseline in height-adjusted total kidney volume (htTKV) as measured by MRI volumetry • Change from baseline in estimated glomerular filtration rate (eGFR), assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation using serum concentrations of creatinine and cystatin C • Change from baseline in the Polycystic Liver Disease Impact (PLD-I) measure score Change from baseline in the Clinical Global Impression of Severity (CGI-S) score • Change from baseline in the Patient Global Impression of Severity (PGI-S) score • Change from baseline in the Patient Global Impression of Change (PGI-C) score • Change from baseline in the Short Form-36 (SF-36) scores • Change from baseline in the Polycystic Liver Disease Questionnaire (PLD-Q) score • Incidence of adverse events (AEs) • Changes from baseline in laboratory values, vital signs and electrocardiogram (ECG) readings • Octreotide plasma concentrations over time |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before Trial start 1. During the screening period (week -12 to -1) During trial phase 2. Week 1 3. Week 13 4. Week 21 5. Week 25 6. Week 39 7. Week 53 8. Week 77
Adverse events are evaluated through put the trial period |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Belgium |
Germany |
Netherlands |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
A Safety Follow-up Visit will be performed 4 weeks after the Week 77/End-of-Treatment Visit.
This is consider as last patient last visit for the trial, end of trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |