PHASE III, MULTI-CENTER, RANDOMIZED, 48 WEEKS, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY TO EVALUATE EFFICACY AND SAFETY OF CER-001 ON VESSEL WALL AREA IN PATIENTS WITH GENETICALLY DEFINED FAMILIAL PRIMARY HYPOALPHALIPOPROTEINEMIA AND RECEIVING BACKGROUND OPTIMIZED LIPID THERAPY - TANGO

Start Date30 May 2016

Sponsor / Collaborator-

NCT02697136

/ TerminatedPhase 3

Phase 3, Multicenter, Randomized, 48 Week, Double Blind, Parallel Group, Placebo Controlled Study to Evaluate Efficacy and Safety of CER-001 on Vessel Wall Area in Patients With Genetically Defined Familial Primary Hypoalphalipoproteinemia

The purpose of this study is to assess the impact of 29 intravenous infusions of CER-001 vs. placebo, given at weekly (9 infusions) and biweekly (20 infusions) intervals on carotid vessel wall area as measured by 3TMRI, when administered to patients with familial primary hypoalphalipoproteinemia with proven CVD and appropriate background lipid-lowering therapy.

Start Date01 Dec 2015

Sponsor / Collaborator

Cerenis Therapeutics, Inc.

100 Clinical Results associated with CER-001

100 Translational Medicine associated with CER-001

100 Patents (Medical) associated with CER-001

Literatures (Medical) associated with CER-001

01 Aug 2024·Current Problems in Cardiology

Can CSL-112 revolutionize atherosclerosis treatment? A critical look at the evidence

Review

Author: Olatunji, Gbolahan ; Yusuf, Ismaila Ajayi ; Ogieuhi, Ikponmwosa Jude ; Odo, Chinenye Cynthia ; Ajibola, Folake ; Obi, Emeka Stanley ; Abraham, Israel Charles ; Aderinto, Nicholas ; Nzeako, Tochukwu ; Kokori, Emmanuel ; Akinmoju, Olumide ; Ajimotokan, Oluwafemi Isaiah ; Olanisa, Olawale

CSL-112, a recombinant human apolipoprotein A-I, holds promise for treating atherosclerotic disease by promoting reverse cholesterol transport. This review evaluates the current evidence on CSL-112's impact on atherosclerotic disease. A search identified studies investigating the effect of CSL-112 on apolipoprotein A-I levels, cholesterol efflux capacity, clinical outcomes, safety profile, pharmacokinetics, pharmacodynamics, and subgroup analysis in patients with atherosclerotic disease. All nine studies consistently demonstrated a dose-dependent increase in apolipoprotein A-I levels following CSL-112 administration. Most studies also reported a corresponding rise in cholesterol efflux capacity. However, the AEGIS-II trial, the largest study to date, did not show a statistically significant reduction in major adverse cardiovascular events in patients with acute myocardial infarction treated with CSL-112 compared to placebo. While some smaller studies suggested potential benefits, particularly in stable atherosclerotic disease, their limitations in size and duration necessitate further investigation. CSL-112 appeared to be generally well-tolerated, with mostly mild or moderate adverse events reported. However, the AEGIS-II trial identified a higher incidence of hypersensitivity reactions in the CSL-112 group, requiring further exploration. CSL-112 demonstrates promise in raising apolipoprotein A-I levels and enhancing cholesterol efflux capacity, potentially promoting reverse cholesterol transport. However, its clinical efficacy for atherosclerotic disease remains unclear. Larger, well-designed trials with longer follow-up periods are necessary to definitively establish its clinical benefit and safety profile before widespread clinical use can be considered. Future research should also explore deeper into the pharmacokinetic and pharmacodynamic profile of CSL-112 and explore its efficacy and safety in different patient subgroups.

01 Dec 2022·Journal of Nuclear Medicine

⁸⁹Zr-Labeled High-Density Lipoprotein Nanoparticle PET Imaging Reveals Tumor Uptake in Patients with Esophageal Cancer

Article

Author: Gisbertz, Suzanne S ; Stroes, Erik S G ; Coolen, Bram F ; van Laarhoven, Hanneke W M ; Gurney-Champion, Oliver ; Nederveen, Aart J ; Vugts, Danielle J ; van Dongen, Guus A M S ; Zheng, Kang H ; Kroon, Jeffrey ; Hulshof, Maarten C C M ; Meijer, Sybren L ; Schoormans, Jasper ; Verberne, Hein J

Nanomedicine holds promise for the delivery of therapeutic and imaging agents to improve cancer treatment outcomes. Preclinical studies have demonstrated that high-density lipoprotein (HDL) nanoparticles accumulate in tumor tissue on intravenous administration. Whether this HDL-based nanomedicine concept is feasible in patients is unexplored. Using a multimodal imaging approach, we aimed to assess tumor uptake of exogenously administered HDL nanoparticles in patients with esophageal cancer. Methods: The HDL mimetic CER-001 was radiolabeled using ⁸⁹Zr to allow for PET/CT imaging. Patients with primary esophageal cancer staged T2 and above were recruited for serial ⁸⁹Zr-HDL PET/CT imaging before starting chemoradiation therapy. In addition, patients underwent routine ¹⁸F-FDG PET/CT and 3-T MRI scanning (diffusion-weighted imaging/intravoxel incoherent motion imaging and dynamic contrast-enhanced MRI) to assess tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability. Tumor biopsies were analyzed for the expression of HDL scavenger receptor class B1 and macrophage marker CD68 using immunofluorescence staining. Results: Nine patients with adenocarcinoma or squamous cell carcinoma underwent all study procedures. After injection of ⁸⁹Zr-HDL (39.2 ± 1.2 [mean ± SD] MBq), blood-pool SUV_mean decreased over time (11.0 ± 1.7, 6.5 ± 0.6, and 3.3 ± 0.5 at 1, 24, and 72 h, respectively), whereas liver and spleen SUV_mean remained relatively constant (4.1 ± 0.6, 4.0 ± 0.8, and 4.3 ± 0.8 at 1, 24, and 72 h, respectively, for the liver; 4.1 ± 0.3, 3.4 ± 0.3, and 3.1 ± 0.4 at 1, 24, and 72 h, respectively, for the spleen) and kidney SUV_mean markedly increased over time (4.1 ± 0.9, 9.3 ± 1.4, and 9.6 ± 2.0 at 1, 24, and 72 h, respectively). Tumor uptake (SUV_peak) increased over time (3.5 ± 1.1 and 5.5 ± 2.1 at 1 and 24 h, respectively [P = 0.016]; 5.7 ± 1.4 at 72 h [P = 0.001]). The effective dose of ⁸⁹Zr-HDL was 0.523 ± 0.040 mSv/MBq. No adverse events were observed after the administration of ⁸⁹Zr-HDL. PET/CT and 3-T MRI measures of tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability did not correlate with tumor uptake of ⁸⁹Zr-HDL, suggesting that a specific mechanism mediated the accumulation of ⁸⁹Zr-HDL. Immunofluorescence staining of clinical biopsies demonstrated scavenger receptor class B1 and CD68 positivity in tumor tissue, establishing a potential cellular mechanism of action. Conclusion: To our knowledge, this was the first ⁸⁹Zr-HDL study in human oncology. ⁸⁹Zr-HDL PET/CT imaging demonstrated that intravenously administered HDL nanoparticles accumulated in tumors of patients with esophageal cancer. The administration of ⁸⁹Zr-HDL was safe. These findings may support the development of HDL nanoparticles as a clinical delivery platform for drug agents. ⁸⁹Zr-HDL imaging may guide drug development and serve as a biomarker for individualized therapy.

01 Jul 2022·Current Atherosclerosis ReportsQ2 · MEDICINE

ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future

Q2 · MEDICINE

Review

Author: Lee, Jane J ; Gibson, C Michael ; Shaunik, Alka ; Ridker, Paul M ; Fitzgerald, Clara ; Duffy, Danielle ; Libby, Peter ; Wright, Samuel D ; Korjian, Serge ; Tricoci, Pierluigi ; Kingwell, Bronwyn A ; Chi, Gerald ; Berman, Gail ; Kazmi, S Hassan ; Kalayci, Arzu

Abstract Purpose of ReviewThe elevated adverse cardiovascular event rate among patients with low high-density lipoprotein cholesterol (HDL-C) formed the basis for the hypothesis that elevating HDL-C would reduce those events. Attempts to raise endogenous HDL-C levels, however, have consistently failed to show improvements in cardiovascular outcomes. However, steady-state HDL-C concentration does not reflect the function of this complex family of particles. Indeed, HDL functions correlate only weakly with serum HDL-C concentration. Thus, the field has pivoted from simply raising the quantity of HDL-C to a focus on improving the putative anti-atherosclerotic functions of HDL particles. Such functions include the ability of HDL to promote the efflux of cholesterol from cholesterol-laden macrophages. Apolipoprotein A-I (apoA-I), the signature apoprotein of HDL, may facilitate the removal of cholesterol from atherosclerotic plaque, reduce the lesional lipid content and might thus stabilize vulnerable plaques, thereby reducing the risk of cardiac events. Infusion of preparations of apoA-I may improve cholesterol efflux capacity (CEC). This review summarizes the development of apoA-I therapies, compares their structural and functional properties and discusses the findings of previous studies including their limitations, and how CSL112, currently being tested in a phase III trial, may overcome these challenges.Recent FindingsThree major ApoA-I-based approaches (MDCO-216, CER-001, and CSL111/CSL112) have aimed to enhance reverse cholesterol transport. These three therapies differ considerably in both lipid and protein composition. MDCO-216 contains recombinant ApoA-I Milano, CER-001 contains recombinant wild-type human ApoA-I, and CSL111/CSL112 contains native ApoA-I isolated from human plasma. Two of the three agents studied to date (apoA-1 Milano and CER-001) have undergone evaluation by intravascular ultrasound imaging, a technique that gauges lesion volume well but does not assess other important variables that may relate to clinical outcomes. ApoA-1 Milano and CER-001 reduce lecithin-cholesterol acyltransferase (LCAT) activity, potentially impairing the function of HDL in reverse cholesterol transport. Furthermore, apoA-I Milano can compete with and alter the function of the recipient’s endogenous apoA-I. In contrast to these agents, CSL112, a particle formulated using human plasma apoA-I and phosphatidylcholine, increases LCAT activity and does not lead to the malfunction of endogenous apoA-I. CSL112 robustly increases cholesterol efflux, promotes reverse cholesterol transport, and now is being tested in a phase III clinical trial.SummaryPhase II-b studies of MDCO-216 and CER-001 failed to produce a significant reduction in coronary plaque volume as assessed by IVUS. However, the investigation to determine whether the direct infusion of a reconstituted apoA-I reduces post-myocardial infarction coronary events is being tested using CSL112, which is dosed at a higher level than MDCO-216 and CER-001 and has more favorable pharmacodynamics.

News (Medical) associated with CER-001

13 Jun 2024

·www.biospace.com

ABIONYX Pharma has completed a successful pre-IND meeting with the FDA for CER-001 Phase 2b/3 Clinical Trial for Patients with Sepsis

Based on encouraging Phase 2a data and a productive pre-IND Type B meeting with U.S. Food and Drug Administration (FDA), ABIONYX Pharma intends to Investigational New Drug application (IND) in the coming months which will include a Phase 2b/3 clinical trial for CER-001 in Sepsis Access here the full press release TOULOUSE, France & LAKELAND, Mich.--(BUSINESS WIRE)-- ABIONYX Pharma, (FR0012616852 - ABNX - eligible for PEA PME), a new generation biotech company dedicated to the discovery and development of innovative therapies based on the world’s only natural recombinant apoA-I, today announced that the company has completed a pre-IND (Investigational New Drug Application, IND) meeting with the US Food and Drug Administration and has received feedback to support an IND filing for its candidate drug. This is an important validation of the quality of the project and a significant step towards an application to include American study centers in future clinical trials. ABIONYX Pharma intends to IND application to the US authority in the coming months. About ABIONYX Pharma ABIONYX Pharma is a next-generation biotech company focused on developing innovative medicines for diseases where there is no effective or existing treatment, even the rarest ones. The company expedites the development of novel therapeutics through an extensive expertise in lipid science and a differentiated apoA-I-based technology platform. ABIONYX Pharma is committed to radically improving treatment outcomes in Sepsis and critical care. View source version on businesswire.com: Contacts Contacts: NewCap Investor relations Nicolas Fossiez Louis-Victor Delouvrier abionyx@newcap.eu +33 (0)1 44 71 98 53 NewCap Media relations Arthur Rouillé abionyx@newcap.eu +33 (0)1 44 71 00 15 Source: ABIONYX Pharma View this news release online at:

INDPhase 2

15 Feb 2024

·www.biospace.com

ABIONYX Pharma Acknowledges the Clinical Results of the Phase 3 AEGIS-II Study Evaluating the Efficacy and Safety of CSL Behring’s Human-plasma-derived apoA-I, CSL112

TOULOUSE, France & LAKELAND, Mich.--(BUSINESS WIRE)-- Access here the full press release ABIONYX Pharma, (FR0012616852 – ABNX – PEA PME eligible), a new generation biotech company dedicated to the discovery and development of innovative therapies based on the world’s only natural recombinant apoA-I, today acknowledges that the Phase 3 AEGIS-II study evaluating the efficacy and safety of CSL Behring’s human-plasma-derived apoA-I, CSL112, compared to placebo in reducing the risk of major adverse cardiovascular events (MACE) in patients following an acute myocardial infarction (AMI), did not meet its primary efficacy endpoint of MACE reduction at 90 days. About CER-001 CER-001 is a novel engineered recombinant human apoA-I that was designed to mimic the structural and functional biological properties of natural, nascent HDL, also known as pre-β HDL, and has been shown to perform all steps of the Reverse Lipid Transport pathway (RLT), the only natural pathway responsible for lipid elimination. Administered CER-001 particles increase transient apoA-I and the number of HDL particles and promote the elimination of trapped cholesterol and lipids in tissues in the absence of LCAT enzyme for example, but also the elimination of bacterial lipid endotoxin (LPS) in the case of sepsis. HDL particles are then recognized by the liver, leading to the elimination of these transported lipids via a process called Reverse Lipid Transport (RLT). About ABIONYX Pharma ABIONYX Pharma is a next-generation biotech company focused on developing innovative medicines in diseases where there is no effective or existing treatment, even the rarest ones. The company expedites the development of novel therapeutics through an extensive expertise in lipid science and a differentiated apoA-I -based technology platform. ABIONYX Pharma is committed to radically improving treatment outcomes in sepsis and critical care. View source version on businesswire.com: Contacts NewCap Investor relations Nicolas Fossiez Louis-Victor Delouvrier abionyx@newcap.eu +33 (0)1 44 71 98 53 NewCap Media relations Arthur Rouillé abionyx@newcap.eu +33 (0)1 44 71 00 15 Source: ABIONYX Pharma View this news release online at:

Phase 3Clinical Result

02 Nov 2023

·www.biospace.com

ABIONYX Pharma RACERS Study Data in Sepsis Presented at the American Society of Nephrology (ASN) 2023 Annual Meeting "Kidney Week"

CER-001 showed robust efficacy in sepsis demonstrating statistically significant sustained reduction in endotoxins (LPS) and consequent decreases in inflammatory cytokines and markers of endothelial dysfunction Data showed a reduced severity of AKI, a trend for decreased mortality and shorter ICU stay CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage with the potential to save lives Simultaneous publication of data from translational sepsis research project, including the RACERS study, exclusively in BMC Medicine (Nature Springer) TOULOUSE, France & LAKELAND, Mich.--(BUSINESS WIRE)-- ABIONYX Pharma, (FR0012616852 - ABNX - PEA PME eligible), a new generation biotech company dedicated to the discovery and development of innovative therapies based on the world's only recombinant human apoA-1, today announced the full results of the RACERS Phase 2 clinical trial of CER-001, an apoA-1-based therapy for the treatment of sepsis, in a late-breaking clinical trial poster presentation at the American Society of Nephrology (ASN) Kidney Week 2023. Key Points from the RACERS Data: CER-001 rapidly and significantly eliminated endotoxins, and the result was maintained (p<0.05 on days 3, 6 and 9), whereas even by day 9, patients on standard care alone showed no decreases in endotoxin levels relative to baseline. Mortality for all patients at 30 days was 6.7% for the CER-001 group and 20.0% for patients treated with standard care alone. This represents a Relative Risk Reduction (RRR) of 65%. Among critical care patients, mortality rates were 14.7% compared to 50.0% for patients on standard care (RRR=71%). ICU patients treated with CER-001 were discharged earlier than patients receiving standard care, with an average ICU stay 5 days shorter than that of patients on standard care. Access here the full press release About ABIONYX Pharma ABIONYX Pharma is a new generation biotech company that aims to contribute to health through innovative therapies in indications where there is no effective or existing treatment, even the rarest ones. Thanks to its partners in research, medicine, biopharmaceuticals and shareholding, the company innovates on a daily basis to propose drugs for the treatment of renal and ophthalmological diseases, or new apoA-I vectors used for targeted drug delivery.

Clinical ResultPhase 2

100 Deals associated with CER-001

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Coronary Syndrome	Phase 2	-	Academic Medical Center University of Amsterdam	-
Atherosclerosis	Phase 2	-	Academic Medical Center University of Amsterdam	-
Familial HDL Deficiency	Preclinical	Belgium	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	Canada	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	United States	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	France	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	Israel	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	Italy	Cerenis Therapeutics, Inc.	01 Dec 2015
Familial HDL Deficiency	Preclinical	Netherlands	Cerenis Therapeutics, Inc.	01 Dec 2015
Homozygous familial hypercholesterolemia	Discovery	Netherlands	Cerenis Therapeutics, Inc.	01 Nov 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EUCTR2020-004202-60-IT (RACERS, ASN2023) Manual	Phase 2	Sepsis	20	CER-001	(nahpuuzokd) = no serious adverse events were attributed to CER-001 use mbstszxwje (rzjuiqjscq )	Positive	02 Nov 2023
				standard of care
NCT02484378 (CARAT, Pubmed \| JAMA Cardiol) Manual	Phase 2	Acute Coronary Syndrome \| Coronary Artery Disease \| Atherosclerosis	293	CER-001	(klswyjbtlz) = lfpmpcdskt iykvplzizh (cgvrtzdzcy ) View more	Negative	01 Sep 2018
				Placebo	(klswyjbtlz) = oxbtyccbad iykvplzizh (cgvrtzdzcy ) View more
NCT01412034 (MODE, Pubmed \| Am Heart J) Manual	Phase 2	Homozygous familial hypercholesterolemia	23	CER-001	eautrlpiyr(rsimwhlvfn) = okudcfoflc galrpcflpq (fxsrrefcia )	Positive	01 May 2015
NCT01201837 (Pubmed \| Eur Heart J)	Phase 2	Acute Coronary Syndrome	507	Placebo	(vinukgikwu) = nqbibdcxgn gduzlaiilq (hpvmlmskgw ) View more	-	07 Dec 2014
				CER-001 3 mg/kg	(vinukgikwu) = zpoemodrxq gduzlaiilq (hpvmlmskgw ) View more

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