Evaluate the effects of CER-001 - adminstered as iv infusion - on plaque size/burden in arteries, plaque inflammation in the artery wall and the rate of cholesterol transport in the body
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Single dose pharmacokinetics of ApoA-I following the first and final doses
* Peak free cholesterol levels (as a surrogate marker for ApoA-I Cmax values)
* Changes in pharmacodynamic parameters over time
Secondary outcome
* Change in cholesterol flux (TICE and TCE) from baseline to Week 26
* Incidence and severity of AEs from routine monitoring
* Incidence of abnormalities and changes from baseline in clinical laboratory
parameters from testing of blood and urine, including antibody development
Background summary
Patients with genetically determined low HDLc have a strongly increased
cardiovascular risk.
To date, no efficient options are available to increase HDLc and thereby
increase the reverse cholesterol transport.
CER-001 has in early studies shown to effectively increase cholesterol
mobilization.
Study objective
Evaluate the effects of CER-001 - adminstered as iv infusion - on plaque
size/burden in arteries, plaque inflammation in the artery wall and the rate of
cholesterol transport in the body
Study design
Prior to the CER-001 infusions, patients will be evaluated for atherosclerotic
plaques (MRI), vessel wall inflammation (PET-CT) and reverse cholesterol
transport rates (cholesterol flux studies).
After a period of CER-001 infusions we will evaluate whether and to what extent
the vessel wall plaques (MRI), vessel wall inflammation (PET-CT) and reverse
cholesterol transport have been improved following CER-001 infusion.
This will be evaluated in an open, non-comaparative investigation in which the
patients will receive infusions of CER-001 (8mg/kg) up to 20 times during a
6-months time phrame.
Intervention
20 times an infusion of CER-001 (8mg/kg), at an interval of 3 days (first four
weeks) followed by weekly administration.
Study burden and risks
To date, no significant side effect following CER-001 infusions have been
observed in the 150 patients who have received these infusions.
During the project, patients will be subjected to the following research:
a. 2x MRI (no radiation)
b. 2x PET-CT: 4.6 mSv ; in total 2x in 4 weeks (resulting in a radiation
exposure well below the legally alowed exposure)
c. cholesterol flux: burden because of the infusions, and frequent collection
of faeces samples, urinary samples and blood withdrawals. No serious side
effects to be expected.
d. 1x 24 u urine (cortisol)
e. 1x synacthen test
The total duration of the research project for a patient will last 6-7 months.
Total volume of blood draws in this period approx. 470 ml.
BP 87519, Rue de la Decouverte 265
LABEGE cedex 31675
FR
BP 87519, Rue de la Decouverte 265
LABEGE cedex 31675
FR
Listed location countries
Age
Inclusion criteria
Eligible subjects must meet the following criteria before they are enrolled into the study:;1. Subject must read and sign the informed consent, as approved by the EC/IRB prior to performance of any screening procedures.
2. Male or female subjects age 18 or above.
3. Females of childbearing potential that agree and commit to use an acceptable form of birth control for the entire study. Acceptable forms of birth control for this study are defined as a barrier method plus hormonal therapy (implants, injections, oral contraceptives and IUDs), double barrier method or abstinence.
4. Subject diagnosis of genetically confirmed homozygous familial ApoA-I deficiency.
5. Subject is on stable dosages of lipid lowering therapies for at least 6 weeks prior to baseline procedures.
6. Subject must be willing to participate in the study and comply with all protocol requirements.
Exclusion criteria
Subjects meeting the following criteria are not eligible for the study:;1. Females who are pregnant, breastfeeding, or plan to become pregnant during the study and males wishing to beget a child during the study..
2. Subject has known major hematologic, renal [serum creatinine > 2.0 mg/dL (180 *mol/L)], hepatic (liver enzymes greater than twice the upper limits of normal for the performing laboratory), metabolic, gastrointestinal or endocrine dysfunction in the judgment of the Investigator.
3. Subject is likely to be unreliable as a study participant based on the Investigator's (or designee*s) knowledge of the subject (e.g., alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
4. Subject has a contraindication to MRI scanning such as imbedded metal (e.g., schrapnel), implanted metal objects (e.g., pacemaker), claustrophobia, allergy to gadolinium chelate contrast or severe renal insufficiency (e.g., GFR < 30 mL/min/1.73m2) that would preclude the use of contrast-enhanced 3TMRI.
5. Subject has received an investigational agent within 30 days prior to baseline procedures.
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 |
|---|---|
| EudraCT | EUCTR2011-006188-23-NL |
| CCMO | NL39219.018.11 |