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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Camurus AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

30 Sep 2022 → ongoing

Decision date (initial)

2023-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Camurus AB

External identifiers

EU CT number

2023-505313-24-00

EudraCT number

2021-003764-27

ClinicalTrials.gov

NCT05281328

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the treatment effect of CAM2029 compared to placebo on liver volume in patients with polycystic liver disease (PLD).

Secondary objectives 12

1. To evaluate the treatment effect of CAM2029 compared to placebo on patient-reported PLD-related symptoms.
2. To evaluate the treatment effect of CAM2029 on liver volume over time in patients with PLD.
3. To evaluate the treatment effect of CAM2029 on patient-reported PLD-related symptoms over time
4. To evaluate the treatment effect of CAM2029 over time on kidney volume in patients with presence of kidney cysts
5. To evaluate the treatment effect of CAM2029 over time on renal function in patients with presence of kidney cysts
6. To evaluate the treatment effect of CAM2029 over time on patient-reported PLD-related impact on functioning and well-being
7. To evaluate the treatment effect of CAM2029 over time on PLD-related symptoms
8. To evaluate the treatment effect of CAM2029 over time on functioning and well-being
9. To evaluate the safety and tolerability of CAM2029
10. To assess the pharmacokinetics (PK) of octreotide after administration of CAM2029
11. To evaluate treatment effect of CAM2029 over time on total liver cyst volume
12. To evaluate the treatment effect of CAM2029 over time on PLD-related symptoms

Conditions and MedDRA coding

Polycystic liver disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Voluntary and valid written informed consent to participate in the trial provided by the patient before any trial related procedures are performed
2. Male or female patient, ≥18 years at screening
3. Diagnosis of PLD (associated with ADPKD or isolated as in ADPLD) with htTLV ≥1800 mL/m at screening
4. 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
5. Not a candidate for, or not willing to undergo, surgical intervention for hepatic cysts during the trial
6. Female patients of childbearing potential must be willing to use an acceptable method of contraception from screening and during the entire trial
7. 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 24

1. Surgical intervention for PLD within 3 months before screening. For sclerotherapy patients, at least 6 months before screening
2. Treatment with an Somatostatin analogue (SSA) within 3 months before screening
3. Non-responsive to previous treatment of PLD with an SSA as per the Investigator’s assessment
4. Symptomatic cholelithiasis within 3 months before screening or previous medical history of cholelithiasis induced by SSAs unless treated with cholecystectomy
5. Presence of extrahepatic cysts that, in the Investigator’s opinion, may prevent the patient from safely participating in the trial
6. Severe kidney disease, as defined by estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2
7. Severe liver disease defined as liver cirrhosis of Child-Pugh class C
8. Use of oral estrogen contraceptives or supplementation within 3 months before screening
9. Poorly controlled diabetes (hemoglobin A1c ≥10%) at screening
10. 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.
11. Uncontrolled hypertension defined by a systolic blood pressure of >160 mmHg and/or diastolic blood pressure of >100 mmHg at screening
12. 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" per www.crediblemeds.org 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 (QTcF) >450 msec for males and >470 msec for females at screening
13. Patients with vascular compromise, including, but not limited to, mesenteric thrombosis, portal hypertension and thrombocytopenia (platelet counts less than 100x109/L)
14. Pregnant, lactating or planning to be pregnant during the trial
15. Clinically significant laboratory abnormalities, which in the opinion of the Investigator may prevent the patient from safely participating in the trial
16. History of solid organ transplantation. Exception for kidney transplant patients
17. Any known allergy, hypersensitivity or intolerance to octreotide or any related drug, or other components of CAM2029, or history of any drug hypersensitivity or intolerance that, in the opinion of the Investigator, would compromise the safety of the patient
18. Contraindications to, or interference with, MRI assessments, as dictated by local hospital regulations
19. Previously treated/randomized in the current clinical trial
20. Participation in any other clinical trial to test an investigational drug or device within the last 30 days before screening or during the trial
21. Any other contraindicated serious medical condition that, in the Investigator’s opinion, may prevent the patient from safely participating in the trial
22. 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
23. Unwilling or unable to comply with the requirements of the protocol or in a situation or condition that, in the opinion of the Investigator, may interfere with participation in the trial
24. On the staff, affiliated with, or a family member of the personnel directly involved with this trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Week 53 in height-adjusted total liver volume (htTLV) as determined by magnetic resonance imaging (MRI) volumetry

Secondary endpoints 15

1. Change from baseline to Week 53 in the Polycystic Liver Disease Symptoms (PLD-S) measure score
2. Change from baseline in htTLV as determined by MRI volumetry
3. Change from baseline in the PLD-S measure score
4. Change from baseline in height-adjusted total kidney volume (htTKV) as measured by MRI volumetry
5. 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
6. Change from baseline in the Polycystic Liver Disease Impact (PLD-I) measure score
7. Change from baseline in the Clinical Global Impression of Severity (CGI-S) score
8. Change from baseline in the Patient Global Impression of Severity (PGI-S) score
9. Change from baseline in the Patient Global Impression of Change (PGI-C) score
10. Change from baseline in the Short Form-36 (SF-36) scores
11. Change from baseline in the Polycystic Liver Disease Questionnaire (PLD-Q) score
12. Incidence of adverse events (AEs)
13. Changes from baseline in laboratory values, vital signs and electrocardiogram (ECG) readings
14. Octreotide plasma concentrations over time
15. Change from baseline in total liver cyst volume determined by MRI volumetry

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Camurus AB

Sponsor organisation

Camurus AB

Address

Rydbergs Torg 4

City

Lund

Postcode

224 84

Country

Sweden

Scientific contact point

Organisation

Camurus AB

Contact name

Senior VP Research & Development

Public contact point

Organisation

Camurus AB

Contact name

Senior VP Research & Development

Third parties 8

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications