Homozygous Familial HypercholesterolemiaPhase 2MODENCT01412034
Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects
A Phase 2 study testing CER-001 in people with Homozygous Familial Hypercholesterolemia, run by Cerenis Therapeutics, SA at 9 sites in 5 countries.
Trial summary
The available medications used to treat HoFH are targeted at reducing circulating levels of total and LDL-cholesterol. These measures can retard the progression of cardiovascular disease, however, they are unlikely to regress existing disease due to years of cholesterol accumulation in the vessel walls and therefore… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- CER-001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Nov 2011to Aug 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female subject 12 years or older
- Subject presents with Homozygous FH
Who cannot join
- Weight >100 kg
- Subjects with significant health problems in the recent past including blood disorders, cancer, or digestive problems
- Female subjects of child-bearing potential
- Known major hematologic, renal , hepatic, metabolic, gastrointestinal or endocrine dysfunction
- Contraindication to MRI scanning that would preclude the use of contrast-enhanced 3TMRI
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Netherlands3 sites
Clinical Research Facility
Amsterdam, 1105AZ
Clinical Research Facility
Maastricht, 6229 HX
Clinical Research Facility
Nijmegen, 6500 HB
United States2 sites
Clinical Research Facility
Hartford, Connecticut, 06102
Clinical Research Facility
North Massapequa, New York, 11758
Canada2 sites
Clinical Research Facility
Chicoutimi, Quebec, G7H 7P2
Clinical Research Facility
Québec, Quebec, G1V4M6
About this study
Official title: Modifying Orphan Disease Evaluation (MODE) Study: A Multicenter, Open-label Study of the Effects of CER-001 on Plaque Volume in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
The available medications used to treat HoFH are targeted at reducing circulating levels of total and LDL-cholesterol. These measures can retard the progression of cardiovascular disease, however, they are unlikely to regress existing disease due to years of cholesterol accumulation in the vessel walls and therefore cannot adequately reduce the existing risk for an ischemic event. HDL has multiple actions that could lead to plaque stabilization and regression, such as rapid removal of large quantities of cholesterol from the vasculature, improvement in endothelial function, protection against oxidative damage and reduction in inflammation. This study will assess the effects of CER-001, a recombinant human Apo-A-1 based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by 3Tesla MRI measurements in patients with HoFH.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- CER-001
- Keywords
- Homozygous Familial Hypercholesterolemia, Familial Hypercholesterolemia, HDL mimetic, ApoA-1
- Medical subject headings
- Homozygous Familial Hypercholesterolemia, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CER-001Drug
Biweekly infusion
| Study group | Role | What they receive |
|---|---|---|
| CER-001 | Experimental | Open label single arm study of CER-001 Receives: Drug: CER-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from baseline to follow-up in carotid mean vessel wall area
Percent change from baseline to follow-up in carotid mean vessel wall area
Measured: Baseline then 6 months and/or ~2 weeks post final dose
Secondary outcomes (1)
Change in carotid vessel wall volume
Percent change in carotid vessel wall volume , as assessed by 3TMRI, from the baseline measurement to the follow up taken ~2 weeks following the final dose of study medication.
Measured: Baseline then 6 months and/or ~2 weeks post final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2011 (estimated)
- Study startNov 2011
- Primary completionOct 2013
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerenis Therapeutics, SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John J. Kastelein, MD PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01412034
- Sponsor's protocol ID
- CER-001-CLIN-003
- Acronym
- MODE
- Status last verified
- Jul 2015
- First submitted
- 5 Aug 2011
- Last updated
- 18 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Eriksson M, Carlson LA, Miettinen TA, Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation. 1999 Aug 10;100(6):594-8. doi: 10.1161/01.cir.100.6.594.
PubMed 10441095Nanjee MN, Doran JE, Lerch PG, Miller NE. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):979-89. doi: 10.1161/01.atv.19.4.979.
PubMed 10195926Nieuwdorp M, Vergeer M, Bisoendial RJ, op 't Roodt J, Levels H, Birjmohun RS, Kuivenhoven JA, Basser R, Rabelink TJ, Kastelein JJ, Stroes ES. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia. 2008 Jun;51(6):1081-4. doi: 10.1007/s00125-008-0975-2. Epub 2008 Apr 4. No abstract available.
PubMed 18389214Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S, Sviridov D, Dart AM. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008 Nov 7;103(10):1084-91. doi: 10.1161/CIRCRESAHA.108.182063. Epub 2008 Oct 2.
PubMed 18832751Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5;290(17):2292-300. doi: 10.1001/jama.290.17.2292.
PubMed 14600188Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007 Apr 18;297(15):1675-82. doi: 10.1001/jama.297.15.jpc70004. Epub 2007 Mar 26.
PubMed 17387133Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, Martin BD, Perlman TJ, Maltais JA, Weissman NJ, Fitzgerald PJ, Brewer HB Jr. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010 Jun 15;55(24):2727-35. doi: 10.1016/j.jacc.2009.12.067.
PubMed 20538165Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002 Mar 26;105(12):1399-402. doi: 10.1161/01.cir.0000013424.28206.8f.
PubMed 11914243
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modifying Orphan Disease Evaluation (MODE) Study: A Multicenter, Open-label Study of the Effects of CER-001 on Plaque Volume in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
- ClinicalTrials.gov ID
- NCT01412034
- Acronym / sponsor ID
- MODE / CER-001-CLIN-003
- Conditions
- Homozygous Familial Hypercholesterolemia
- Keywords
- Homozygous Familial Hypercholesterolemia, Familial Hypercholesterolemia, HDL mimetic, ApoA-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Cerenis Therapeutics, SAIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 8 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The available medications used to treat HoFH are targeted at reducing circulating levels of total and LDL-cholesterol. These measures can retard the progression of cardiovascular disease, however, they are unlikely to regress existing disease due to years of cholesterol accumulation in the vessel walls and therefore cannot adequately reduce the existing risk for an ischemic event. HDL has multiple actions that could lead to plaque stabilization and regression, such as rapid removal of large quantities of cholesterol from the vasculature, improvement in endothelial function, protection against oxidative damage and reduction in inflammation. This study will assess the effects of CER-001, a recombinant human Apo-A-1 based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by 3Tesla MRI measurements in patients with HoFH.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CER-001 | Experimental | Drug: CER-001Open label single arm study of CER-001 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female subject 12 years or older
- Subject presents with Homozygous FH
Key exclusion criteria (5 listed)
- Weight >100 kg
- Subjects with significant health problems in the recent past including blood disorders, cancer, or digestive problems
- Female subjects of child-bearing potential
- Known major hematologic, renal , hepatic, metabolic, gastrointestinal or endocrine dysfunction
- Contraindication to MRI scanning that would preclude the use of contrast-enhanced 3TMRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CER-001Biweekly infusion | Drug | CER-001 |
Primary outcome
Percent change from baseline to follow-up in carotid mean vessel wall area
Time frame: Baseline then 6 months and/or ~2 weeks post final dose
Percent change from baseline to follow-up in carotid mean vessel wall area
1 secondary outcome
Change in carotid vessel wall volume
Time frame: Baseline then 6 months and/or ~2 weeks post final dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2015.
- Background: PubMed 10441095Eriksson M, Carlson LA, Miettinen TA, Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation. 1999 Aug 10;100(6):594-8. doi: 10.1161/01.cir.100.6.594.
- Background: PubMed 10195926Nanjee MN, Doran JE, Lerch PG, Miller NE. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):979-89. doi: 10.1161/01.atv.19.4.979.
- Background: PubMed 18389214Nieuwdorp M, Vergeer M, Bisoendial RJ, op 't Roodt J, Levels H, Birjmohun RS, Kuivenhoven JA, Basser R, Rabelink TJ, Kastelein JJ, Stroes ES. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia. 2008 Jun;51(6):1081-4. doi: 10.1007/s00125-008-0975-2. Epub 2008 Apr 4. No abstract available.
- Background: PubMed 18832751Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S, Sviridov D, Dart AM. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008 Nov 7;103(10):1084-91. doi: 10.1161/CIRCRESAHA.108.182063. Epub 2008 Oct 2.
- Background: PubMed 14600188Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5;290(17):2292-300. doi: 10.1001/jama.290.17.2292.
- Background: PubMed 17387133Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007 Apr 18;297(15):1675-82. doi: 10.1001/jama.297.15.jpc70004. Epub 2007 Mar 26.
- Background: PubMed 20538165Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, Martin BD, Perlman TJ, Maltais JA, Weissman NJ, Fitzgerald PJ, Brewer HB Jr. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010 Jun 15;55(24):2727-35. doi: 10.1016/j.jacc.2009.12.067.
- Results publication: PubMed 11914243Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002 Mar 26;105(12):1399-402. doi: 10.1161/01.cir.0000013424.28206.8f.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John J. Kastelein, MD PhD principal investigator
Amsterdam UMC, location VUmc
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CER-001 in people with Homozygous Familial Hypercholesterolemia, run by Cerenis Therapeutics, SA at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Netherlands, United States, Canada, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change from baseline to follow-up in carotid mean vessel wall area (time frame: Baseline then 6 months and/or ~2 weeks post final dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01412034, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2015.