Frank Dietrich Wagner

Charité Universitätsmedizin Berlin | Charité · Charité Research Organisation

Long-COVID, post-acute Covid-19 syndrome, post-infectious syndromes, chronic fatigue syndrome, brain fog, immunoadsorption, autoimmunity, endothelial dysfunction, mitochondrial dysfunction, clinical trials

Background The interleukin-22 cytokine (IL-22) has demonstrated efficacy in preclinical colitis models with non-immunosuppressive mechanism of action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallisable fragment (Fc) of human IgG 4 for improved pharmacokinetic characteristics, but with a mutation to min...

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiot...

Licogliflozin versus placebo in women with polycystic ovary syndrome (PCOS): a randomised, double-blind, phase 2 trial. Introduction: PCOS is characterised by hyperandrogenism and insulin resistance. The dual sodium-glucose transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesit...

Heart transplantation has extended the lives of many patients with end-stage heart failure. Although beset with the arduous aftermaths of immunosuppression, those who survived live meaningful lives similar to that of the general population. In this series, heart transplantation has led to a considerable extension of life span of >31-34 years. Devel...

Over time, various surgical treatment strategies have evolved to manage advanced heart failure (HF). Scientific and technological breakthroughs through the last 50 years have put forward various surgical alternatives to patients with advanced HF encompassing surgical ventricular restoration to surgical gene therapy and stem cell replacement of the...

To evaluate efficacy and safety of BGG492 (selurampanel; an orally active, competitive AMPA glutamate receptor antagonist) in patients with moderate-to-catastrophic chronic subjective tinnitus. Study (NCT01302873) enrolled patients with subjective tinnitus based on THI severity grade 3, 4 or 5 (moderate, severe or catastrophic), and those with chro...

BACKGROUND: Helicobacter pylori (Hp) eradication therapy can alter gut microbiota, provoking gastro-intestinal (GI) symptoms that can be improved by probiotics. The effect on Hp patients of a Test fermented milk containing yogurt and three Lacticaseibacillus (L. paracasei CNCM I-1518, CNCM I-3689, L. rhamnosus CNCM I-3690) strains was assessed on a...

Objectives: To apply serial ultrasound (US) assessments to show effects of ianalumab (anti-BAFF-R monoclonal antibody) on inflamed salivary glands of patients with primary Sjögren's syndrome (pSS). Methods: In a single-centre, 24-week double-blind study (NCT02149420), 27 pSS patients of moderate-to-severe activity were randomly assigned to recei...

Background Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction. Methods We studied the effects of danicamtiv on LV and LA function in non‐clinical st...

Objectives To evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren’s syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study. Methods Patients with pSS, EULAR Sjögren’s Syndrome Disease Activit...

Aims To evaluate the safety, pharmacokinetics, and pharmacodynamics of SAR425899, a novel polypeptide active as an agonist at both the glucagon‐like peptide‐1 receptor (GLP‐1 R) and the glucagon receptor, in healthy volunteers and in patients with overweight/obesity and type 2 diabetes. Methods Subcutaneous administrations of SAR425899 were tested...

Purpose: Elbasvir (MK-8742) and grazoprevir (MK-5172; Merck & Co, Inc, Kenilworth, New Jersey) are hepatitis C virus (HCV)-specific inhibitors of the nonstructural protein 5A phosphoprotein and the nonstructural protein 3/4A protease, respectively. The aims of these studies were to evaluate the antiviral activity and safety of different doses of e...

PurposeThe CD40–CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis. The safety, pharmacokinetics and pharmacodynamics of BI 655064, a novel humanised antagonistic anti-CD40 monoclonal antibody, were investigated in this first-in-human trial. Methods He...

Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and L...

Objective: Tumor necrosis factor (TNF) and interleukin (IL)-17 independently contribute to the pathophysiology of rheumatoid arthritis (RA). ABT-122 is a novel dual variable domain immunoglobulin that selectively and simultaneously targets human TNF and IL-17A in an effort to evoke a greater clinical response than targeting either cytokine alone....

Background and objective: Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects. Methods: Subjects received metform...

Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the ef...

Background: Arterial hypertension and the resulting reduction in aortic distensibility impose increased hemodynamic load to the left ventricle and, if untreated may lead to left ventricular hypertrophy (LVH) and heart failure. Purpose: We analyzed the effects of LCZ696 on LV-structure and function as well as on regional and global aortic distensibi...

Background VAY736 is a novel, defucosylated, human IgG1 mAb targeting the receptor for B cell activating Factor of the TNF family (BAFF-R), providing both enhanced antibody-dependent cellular cytotoxicity (ADCC)-mediated depletion of B cells and blockade of BAFF:BAFF-R signaling that drives B cell differentiation, proliferation and survival. Objec...

Background TNF and IL-17 independently contribute to the pathophysiology of RA, synergistically inducing inflammatory mediators and joint destruction. Selective dual neutralization of TNF and IL-17 confers superior protection vs inhibition of either alone in mouse RA models. ABT-122 is a novel dual variable domain immunoglobulin (DVD-Ig™) targeting...

Background and aims: Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, t...

Objective: To assess the antiviral activity, pharmacokinetics, and safety of doravirine in nonnucleoside reverse transcriptase inhibitor-naïve, HIV-infected male patients. Design: Double-blind, randomized, two-panel, dose-escalation study. Methods: In two sequential panels, 18 patients received doravirine [25 mg (Panel A) or 200 mg (Panel B)]...

Background The CD40-CD40L pathway may play a major role in autoimmune disorders like rheumatoid arthritis (RA). Blocking this pathway may be a promising new treatment for RA-patients. BI 655064 is a novel humanized antagonistic anti-CD40 monoclonal antibody, free of agonistic activity and without antibody-dependent cellular- or complement-dependent...

To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (regi...

Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. This study was primarily designed to investigate the effect of a low-fat...

The objective of this paper is to investigate the safety, pharmacokinetics (PK) and immunogenicity of CDP7657, a PEGylated anti-CD40L antibody fragment, in healthy individuals and patients with systemic lupus erythematosus (SLE). This randomized, double-blind, single-dose, dose-escalation phase I study consisted of two parts. In part 1, 28 healthy...

IL-23 is associated with plaque psoriasis susceptibility and pathogenesis. BI 655066 is a fully human IgG1 mAb specific for the IL-23 p19 subunit. This first-in-human proof-of-concept study evaluated the clinical and biological effects of BI 655066 in patients with moderate-to-severe plaque psoriasis. We performed a single-rising-dose, multicenter,...

Aim: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers....

Background The monoclonal antibody NNC0215-0384 blocks the complement factor 5a receptor (C5aR), mainly expressed on leukocytes, and thereby inhibits the proinflammatory signaling mediated via C5aR, which is thought to play an important role in rheumatoid arthritis (RA).1 NNC0215-0384 is currently in clinical development as a 2nd generation compoun...

In order to evaluate the potential for CYP3A4 induction by moxidectin, midazolam pharmacokinetic (PK) parameters were compared before and after moxidectin administration. Healthy subjects received a single 8 mg dose of moxidectin and 3 single 7.5 mg doses of midazolam 3 days before, and 7 and 89 days after the moxidectin. Blood samples were taken f...

Dabigatran, a specific, reversible direct thrombin inhibitor, is used to prevent ischaemic and haemorrhagic strokes in patients with atrial fibrillation. As with every anticoagulant, there is a need to rapidly reverse its effects in emergency situations. In an open-label, single-centre phase I study with two fixed multiple dosing periods, we invest...

Background: Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel To...

Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment immunoglobulin E (IgE) ≤700 IU/ml. To extend current dosing tables, we evaluated the potential of high omalizumab doses to block allergen-induced bronchoconstriction in patients with higher IgE levels. Methods: Asthmatic...

The aim of this study was to compare the single-dose effects of thiazide-type diuretics cicletanine and hydrochlorothiazide (HCTZ), on natriuresis and kaliuresis in prehypertensive and treatment-naïve, stage 1 hypertensive patients and to explore the impact of GRK4 gene polymorphisms on thiazide-induced urinary electrolyte excretion. The study was...

Indacaterol is a novel, inhaled once-daily ultra long-acting β2-agonist for the treatment of COPD. This randomised, double-blind, placebo-controlled, two-period crossover study evaluated the effect of two-week treatment with indacaterol 300 μg on peak and isotime exercise inspiratory capacity (IC) in patients with COPD. Patients (40-80 years) with...

Unlabelled: More effective and better-tolerated therapies are needed for chronic hepatitis C virus (HCV) infection. Among the direct-acting anti-HCV agents in development is the nonstructural 5B protein (NS5B polymerase) non-nucleoside inhibitor filibuvir. We investigated the antiviral activity, pharmacokinetics, safety, and tolerability of multip...

Casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure (BP) in long-term clinical studies. Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a ferm...

In cardiac transplantation postoperative right ventricular dysfunction is a major cause of mor-bidity and mortality. Recipients with pulmonary hypertension due to end-stage heart failure and a donor heart, fragile because of ischemia-reperfusion injury, and not previously adapted to an elevated pulmonary resistance are the causes of right ventricul...

Raltegravir is a human immunodeficiency virus-1 (HIV-1) integrase strand transfer inhibitor metabolized by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). In this study, 30 subjects with a UGT1A1*28/*28 genotype (associated with decreased activity of UGT1A1) and 27 UGT1A1*1/*1 control subjects (matched by race, age, gender, and body m...

Background: RAL is a HIV-1 integrase strand transfer inhibitor with potent in vitro and in vivo activity against HIV-1. The primary metabolic pathway of RAL involves glucuronosyl transferase enzymes, primarily the UGT1A1 isoform. Due to the substantive prevalence of individuals with decreased UGT1A1 activity, this study investigated the pharmacokin...

Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem. We investigated the safety and efficacy of CYT006...

SCH 503034 is a novel and potent oral hepatitis C virus (HCV) protease inhibitor. In this phase Ib study, we assessed safety parameters and virologic response of combination of SCH 503034 plus pegylated (PEG) interferon (IFN) alpha-2b in patients with HCV genotype 1 infections who were previously nonresponders to PEG-IFN-alpha-2b +/- ribavirin ther...

Despite the availability of efficacious drugs, the success of treating hypertension is limited by patients' inconsistent drug intake. Immunization against angiotensin II may offer a valuable alternative to conventional drugs for the treatment of hypertension, because vaccines induce relatively long-lasting effects and do not require daily dosing. H...

In patients with renal disease increased urotensin II plasma levels have been observed. We have investigated whether palosuran, a potent, selective, and competitive antagonist of the urotensin II receptor, has effects in patients who are prone to the development of renal disease. Macroalbuminuric, diabetic patients, categorized by renal function, w...

To compare the pharmacokinetics, pharmacodynamics, and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1. Thirty-six patients were randomised to peginterferon alfa-2b (1.5 microg/kg/week) or peginterferon alfa-2a (180 microg/week) for 4 weeks, then in combination with ribavir...

Left ventricular assist device (LVAD) implantation and heart transplantation (HTx) are established therapeutic approaches in the treatment of end-stage heart failure. The postoperative humoral responses to the two treatments have not yet been compared. All patients were treated with inhaled nitric oxide (iNO) on weaning from cardiopulmonary bypass...

The authors assessed the impact of severe hepatic impairment on the disposition of fingolimod--a sphingosine-1-phosphate receptor immunomodulator primarily metabolized by CYP4F2--in 6 patients and 6 matched healthy controls who received a single 5-mg oral dose. Compared with healthy controls, severe hepatic-impaired subjects had a doubled area unde...

In patients with inotrope-dependent end-stage heart failure the timely application of the most suitable treatment, i.e. heart transplantation, implantation of a ventricular assist device or conservative treatment, is a key issue for therapeutic success. Seventy-six inotrope-dependent patients with end-stage heart failure were enrolled. Measurements...

Objectives: Some patients with heart failure (HF) remain stable until a donor heart becomes available while others need mechanical circulatory support due to rapid hemodynamic deterioration. Several serum markers were found elevated in chronic HF, but it is unknown which marker may predict hemodynamic decompensation. We evaluated whether serum mark...

A dysfunctional pulmonary vascular endothelium with diminished release of nitric oxide (NO) and increased expression of endothelin-1 is thought to be the main pathophysiological inductive mechanism for acute pulmonary hypertension. New therapeutic approaches are aimed at ameliorating endothelial dysfunction in acute pulmonary hypertension. Whether...

Inhaled nitric oxide (iNO) therapy is an effective treatment of pulmonary hypertension following left ventricular assist device (LVAD) implantation. As iNO may also modulate circulating endothelin-1 (ET-1) and big endothelin following LVAD implantation, we investigated the effects of iNO on ET-1 and big endothelin plasma concentration gradients. In...

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Cardiac troponin T (cTnT) >0.1 microg/l and procalcitonin (PCT) >2 microg/l in the serum of heart donors are predictors of early graft failure after heart transplantation (HTx). The current study investigates the relationship between these two markers and their prognostic value when one or both of them are elevated. Cardiac TnT and PCT were measure...

Inhaled nitric oxide (iNO) is an established therapy in the treatment of pulmonary hypertension and right ventricular dysfunction following left ventricular assist device implantation. Since it is known that endothelin-1 contributes to pulmonary hypertension, and nitric oxide modulates endothelin-1 synthesis in vitro, we investigated the effects of...

Angiotensin-converting enzyme inhibitors are an effective therapy for all stages of heart failure due to reduced systolic left ventricular function. Because sufficient data on intravenous angiotensin-converting enzyme inhibitors following coronary artery bypass surgery complicated by postoperative left ventricular dysfunction are unavailable, the e...

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The increasing demand to improve the quality of clinical research has been addressed in recent years in Germany. In a response designed to overcome the shortcomings of existing collaboration between academic institutions, contract research organisations (CROs), and the pharmaceutical industry, clinical study centres have been initiated and funded b...

Als wesentlicher pathophysiologischer Mechanismus für das Auftreten einer pulmonalen Hypertonie wird heute eine Dysfunktion des pulmonalvaskulären Endothels mit verminderter Freisetzung von NO und vermehrter Expression von Endothelin-1 verstanden. Neue Therapieansätze sollen diese endotheliale Dysfunktion bei der akuten pulmonalen Hypertonie behebe...

Ziel dieser Arbeit war es, neue Therapieprinzipien zu entwickeln und zu überprüfen, ob diese geeignet sind, ein Rechtsherzversagen nach Implantation eines LVAD bei Patienten mit terminaler Herzinsuffizienz zu verhindern. Bei Patienten mit chronischem Linksherzversagen erhöht sich der pulmonalvaskuläre Widerstand. Als Ursache wird eine Dysregulation...

Background To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mor...