This study has been transitioned to CTIS with ID 2023-505313-24-00 check the CTIS register for the current data. To evaluate the treatment effect of CAM2029 compared to placebo on liver volume in patients with polycystic liver disease (PLD)
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline to Week 53 in height-adjusted total liver volume (htTLV)
as determined by magnetic resonance imaging (MRI) volumetry
Secondary outcome
Change from baseline to Week 53 in the Polycystic Liver Disease Symptoms
(PLD-S) measure score
Background summary
Polycystic liver disease (PLD) is a rare genetic disorder defined by the
formation of multiple fluid-filled cysts in the liver. In adults, PLD can occur
independently in the liver as in autosomal dominant PLD (ADPLD) (also commonly
referred to as PCLD), but it is also a common accompanying condition to
autosomal dominant polycystic kidney disease (ADPKD).
Liver transplantation is currently the only cure for PLD but only a minority of
patients with the most severe symptoms qualify for this intervention. Other
surgical treatments such as percutaneous sclerotherapy, transarterial
embolization, cyst fenestration and hepatic resection are indicated to
specific groups of patients with PLD. Although surgical therapies may be
successful in reducing liver volume in selected patients, they can also cause
signi*cant morbidity and mortality. Most surgical interventions are also only
partially effective and associated with a high rate of
reoccurrence, and most importantly, are unable to change the natural course of
the disease.
There is currently no approved pharmacological treatment for PLD, but different
drugs have been tested. Somatostatin analogues (SSAs), including lanreotide and
octreotide, have been shown to inhibit the growth of hepatic cysts by reducing
cAMP in experimental animal studies.
CAM2029 (*octreotide subcutaneous depot*) is a novel and long-acting
subcutaneous (SC) injection depot based on the active substance octreotide and
formulated with Camurus* proprietary FluidCrystal® injection depot technology.
It is provided as a pre-filled pen with no need for reconstitution and offers
the option of self- or partner-administration at home.
Therefore, compared to the currently available long-acting octreotide product
Sandostatin LAR, which is administered as an intramuscular injection with a
syringe and which needs reconstitution before injection, CAM2029 may be easier
to handle and to administer, thereby potentially improving patient convenience
and care. In addition, the bioavailability of octreotide has been shown to be
higher for CAM2029 than for Sandostatin LAR (31).
Study objective
This study has been transitioned to CTIS with ID 2023-505313-24-00 check the CTIS register for the current data.
To evaluate the treatment effect of CAM2029 compared to placebo on liver volume
in patients with polycystic liver disease (PLD)
Study design
This is a Phase 2/3, randomized, placebo-controlled, double-blind, multi-center
trial designed to evaluate the efficacy and safety of 2 treatment regimens of
CAM2029 versus placebo in patients with PLD.
The trial consists of a 4-week Screening Period followed by a 52-week
(12-month) Treatment Period for which approximately 69 patients will be
randomized in a 1:1:1 ratio to 1 of the 3 treatment arms:
• Arm 1: CAM2029 10 mg once weekly
• Arm 2: CAM2029 10 mg once every 2 weeks (weekly alternation with placebo)
• Arm 3: Placebo once weekly
Following completion of the Treatment Period, all patients will continue to a
24-week, open-label, single-arm, Extension Period with CAM2029 10 mg once
weekly, followed by a 4-week Safety Follow-Up Period.
Intervention
CAM2029
During the Treatment Period, CAM2029 10 mg (0.5 mL) will be administered as an
SC injection using a pre-filled pen once weekly in treatment arm 1 and every 2
weeks in treatment arm 2 (weekly alternation with placebo). During the
Extension Period, CAM2029 10 mg (0.5 mL) will be administered as an SC
injection using a pre-filled pen once weekly. Injections will be administered
in the abdomen, thigh or buttock. Self- or partner-administration of CAM2029
will be encouraged after appropriate training, including at least 1 self- or
partner-administration under the supervision of trial personnel who has been
adequately trained.
Comparator Product (Placebo)
During the Treatment Period, placebo (0.5 mL) will be administered as an SC
injection using a pre-filled pen every 2 weeks in treatment arm 2 (weekly
alternation with CAM2029) and once weekly in treatment arm 3. Injections will
be administered in the abdomen, thigh or buttock. Self- or
partner-administration of CAM2029 will be encouraged after appropriate
training, including at least 1 self- or partner-administration under the
supervision of trial personnel who has been adequately trained.
Study burden and risks
The side effects reported during the clinical studies with CAM2029 in healthy
volunteers and patients were similar to those listed for octreotide hereunder:
• Diarrhea
• Abdominal pain
• Nausea (feeling sick)
• Constipation
• Flatulence (the presence of excessive gas)
• Headache
• Gall bladder stones
• Increased blood sugar levels
• Injection site reactions
Some of the tests and procedures performed during this study may cause side
effects that are not related to the study treatment:
Blood drawing; ECG; Discomfort due to completion of study questionnaires and
assessments; MRI scans;
Ideon Science Park Ideongatan 1A-D
Lund SE 223-70
SE
Ideon Science Park Ideongatan 1A-D
Lund SE 223-70
SE
Listed location countries
Age
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 >=2500 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
- Female patients of childbearing potential must be willing to use an
acceptable method of contraception from screening and during the entire trial
- Male patients must be willing to use condom as method of contraception from
screening and throughout the trial unless they have been sterilized by
vasectomy (with an appropriate post-vasectomy documentation of the absence of
sperm in the ejaculate)
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
• 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
• Contraindications to, or interference with, MRI assessments, as dictated by
local hospital regulations
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-505313-24-00 |
| EudraCT | EUCTR2021-003764-27-NL |
| CCMO | NL79984.091.22 |