This study has been transitioned to CTIS with ID 2023-509029-29-00 check the CTIS register for the current data. In this study, we look at how safe the new medicinal product ISIS 678354 is for the treatment of FCS. And how well it works.
ID
Source
Brief title
OLE
Condition
- Metabolic and nutritional disorders congenital
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety endpoints include a proportion of patients who show the following
changes from Baseline to Week 53, week 105 and week 157:*
• Decrease in platelet count by >= 30%
• Decrease in platelet count by >= 50%
• Platelet count value < 50,000 mm3
• Major bleeding events
• Clinically relevant non-major bleeding events
• Decrease in estimated glomerular filtration rate (eGFR) by >= 30%
• Decrease in eGFR by >= 50%
• Urine protein-Creatine ratio (UPCR) >= 1000 mg/g
• Urine albumin-creatine ratio (UACR) >= 500 mg/g
• alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 5 ×
upper limit of normal (ULN)
• Total bilirubin >= 2.0 mg/dL
• ALT or AST >= 3 × ULN and total bilirubin >= 2 × ULN
* Lab values based on confirmed results
In addition, rate of major adverse cardiovascular event (MACE) will be
summarized.
Secondary outcome
The efficacy endpoints are the following:
• Percent change in fasting triglcycerides (TG) from Baseline at month 6
(average of Weeks 23, 25 and 27)
• Percent change in fasting TG from Baseline at month 12 (average of Week 51
and 53), month 24 (average of week 103 and 105) , and month 26 (average of week
155 and 157)
• Proportion of patients who achieve >= 40% reduction in fasting TG from
Baseline at month 6
• Proportion of patients who achieve >= 40% reduction in fasting TG from
Baseline at month 12, 24, 36
• Percent change in fasting apoC-III from Baseline at Month 6
• Percent change in fasting apoC-III from Month 12, 24, 36
• Percent change in fasting apoprotein B48 (apoB48) from Baseline at month 6
• Percent change in fasting apoB48 from Baseline at month 12, 24, 36
• Percent change in fasting non-HDL-C from Baseline at Month 6
• Percent change in fasting non-HDL-C from Months 12, 24, 36
• Proportion of patients who achieve fasting TG <= 880 mg/dL at month 6
• Proportion of patients who achieve fasting TG <= 880 mg/dL at month 12, 24, 36
• Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1
through Week 53, 105 or 157), in patients with >= 2 events of adjudicated acute
pancreatitis in 5 years prior to treatment with Study Drug in the index study
• Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1
through Week 53, 105 or 157)
• Adjudicated acute pancreatitis event rate during the Treatment Period
(Week 1 through Weeks 53, 105, or 157) in patients with a prior history of
pancreatitis within 10 years prior to Screening in the index study
• Proportion of patients who achieve >= 70% reduction in fasting TG from
Baseline at month 6
• Proportion of patients who achieve >= 70% reduction in fasting TG from
Baseline at month 12, 24, 36
• Proportion of patients who achieve fasting TG <= 500 mg/dL at month 6
• Proportion of patients who achieve fasting TG <= 500 mg/dL at month 12, 24, 36
Exploratory endpoint:
Health care utilization: Emergency room (ER) visits, hospitalizations, and
total in-patient days
Patient perceived meaningful change in FCS-SIS
Pharmacokinetics endpoint
Pharmacokinetic exposure over time and potential exposure-response analysis
using relevant exposure parameters and biomarkers
Background summary
Familial Chylomicronemia Syndrome (FCS) is a disease passed on through
families. People with FCS have high amounts of fats in their blood. People
with FCS may get fat deposits on their skin. They often experience frequent and
severe abdominal pain (stomach area), repetitive cramps and are at a higher
risk of developing inflammation of the pancreas. The pancreas is an organ
required for a good digestion and blood sugar level. Inflammation of the
pancreas can cause severe pain in the stomach area and often requires long
stays in the hospital.
Apoliprotein C-III (ApoC-III) is found in blood and increases the fat levels in
the blood. The study drug, ISIS 678354, reduces the amount of apoC-III in the
blood. This may help people lower the fat in the blood. The study drug could be
a treatment for FCS. Health authorities have not approved the study drug for
the treatment of FCS. The study drug has previously been tested in healthy
volunteers and patients with heart disease and elevated fat levels.
Study objective
This study has been transitioned to CTIS with ID 2023-509029-29-00 check the CTIS register for the current data.
In this study, we look at how safe the new medicinal product ISIS 678354 is for
the treatment of FCS. And how well it works.
Study design
This study is an open label extension study of the Balance study (ISIS
678354-CS3). This study will provide the participant with extended treatment of
Familial Chylomicronemia Syndrome (FCS) with the study drug. An *open-label*
study means that both the participant and the investigator are aware that the
participant will be treated with the study drug, ISIS 678354.
During this study, there will be 50 visits during 174 weeks. There are 3
periods to this study:
1. Screening (2 visits): up to 31 days (4 weeks)
Some tests will be performed to see whether the participant is eligible
to participate.
2. Study Treatment (45 visits): 157 weeks
If the participant is eligible, the participant will move to the
treatment. The participant will be treated for 157 weeks with the study drug
(ISIS
678354).
The study drug will be given at the dose of 80 mg once every 4 weeks
(39 times). The study drug will be administered by using either a syringe
containing the study drug that was drawn up from a vial, or an autoinjector
that already contains the study drug.
The 80 mg dose of the study drug may be adjusted to 50 mg every 4 weeks
(temporarily or permanently) for tolerability or safety reasons.
The participant will receive the study drug as under the skin
injections in your abdomen (stomach area), thigh, or upper arm.
3. Post-treatment Follow-up (3 visits): 13 weeks
Intervention
The study drug (IISIS 678354) is expected to effectively lower triglyceride
levels in patients with Familial Chylomicronemia Syndrome and may have the
potential to reduce events of pancreatitis in patients with Familial
Chylomicronemia Syndrome.
The study drug will be given at the dose of 80 mg once every 4 weeks (39
times). The 80 mg dose of the study drug may be adjusted to 50 mg every 4 weeks
(temporarily or permanently) for tolerability or safety reasons. The study drug
will be administered as under the skin injections in your abdomen (stomach
area), thigh, or upper arm. The study drug will be administered by using either
a syringe containing the study drug that was drawn up from a vial, or an
autoinjector that already contains the study drug.
Study burden and risks
Burden: During the study, there will be 50 visits. Subjects will be treated
with the study drugs once every 4 weeks for a total of 39 times. Physical and
vital signs examinations, ECG (assessment electrical activity of the heart),
blood and urine test will be performed. These assessments can be associated
with some discomforts (e.g. taking blood can be painful, skin irritation can
arise due to the electrodes of the ECG, fasting can cause
faintness).Information about adverse events will be collected during the
study. Participants will be asked to not consume alcohol and are encouraged to
follow a low-fat diet (<20 gram fat per day) during the study. Diet and alcohol
counseling will be provided.
Risk: The study drug may cause side effects. Common side effects are redness,
bruising and itching at the site of injection. Those effects normally disappear
within a week.
Less common side effects are:
• Mild flu-like symptoms (fever, chills, muscle aches, nausea or vomiting)
could also occur during the first or second treatment. These symptoms typically
resolve on its own on the same day or the day after.
• The study drug could affect the kidney. Blood and urine will be collected
during the study to check these organs.
Benefit: The study drug may treat FCS but that is not certain. FCS may come
back or get worse at any time during this study
Gazelle Court 2855
Carlsbad CA 92010
US
Gazelle Court 2855
Carlsbad CA 92010
US
Listed location countries
Age
Inclusion criteria
1. Must have given written informed consent (signed and dated) and any
authorizations
required by local law and be able to comply with all study requirements
2. Satisfactory completion of the ISIS 678354-CS3 index study (last dose as
scheduled at Week 49) with an acceptable safety profile, per Investigator
judgement
3. Willing to follow a diet comprising <= 20 g fat per day during the study
4. Satisfy the following:
a. Females: must be non-pregnant and non-lactating and either:
i. surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral
salpingectomy,
bilateral oophorectomy)
ii. postmenopausal (defined as 12 months of spontaneous amenorrhea in females
> 55 years of age or, in females <= 55 years, 12 months of spontaneous amenorrhea
without an alternative medical cause and follicle-stimulating hormone (FSH)
levels in the postmenopausal range for the laboratory involved)
iii. abstinent* or
iv. if engaged in sexual relations of child-bearing potential, agree to use a
highly
effective contraceptive method from the time of signing the informed consent
form until at least 30 weeks after the last dose of ISIS 678354
b. Males: Surgically sterile, abstinent* or if engaged in sexual relations with
a female of
child-bearing potential, agree to use a highly effective contraceptive method
from the
time of signing the informed consent form until at least 30 weeks after the
last dose of
ISIS 678354
* Abstinence is only acceptable as true abstinence, i.e., when this is in line
with the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar,
ovulation, symptothermal, post-ovulation methods), declaration of abstinence for
the duration of a trial, and withdrawal are not acceptable methods of
contraception
5. The following concomitant medications will be allowed if dosing regimen is
expected to
remain constant through the end of the study (occasional or intermittent use of
over-the-counter (OTC) medications will be allowed at Investigator*s
discretion):
a. Statins, omega-3 fatty acids (prescription and OTC), fibrates, or other
lipid-lowering
medications. Patients taking OTC omega-3 fatty acids should make every effort to
remain on the same brand through the end of the study
b. Antidiabetic medications except glucagon-like peptide 1(GLP-1) agonist that
is disallowed
c. Antihypertensive medications
d. Oral anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, and apixaban)
and
regular clinical monitoring is performed
e. Tamoxifen, estrogens or progestins
f. Atypical antipsychotic medications (e.g., olanzapine and clozapine)
Exclusion criteria
1. Have any new condition or worsening of existing condition which in the
opinion of the
Investigator would make the patient unsuitable for enrollment, or could
interfere with the
patient participating in or completing the study, including need for treatment
with
medications disallowed in the index study (ISIS 678354-CS3).
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 | CTIS2023-509029-29-00 |
| EudraCT | EUCTR2021-003280-95-NL |
| ClinicalTrials.gov | NCT05130450 |
| CCMO | NL80238.000.22 |