A Randomized, Open Label, Parallel-Group Study to Estimate Bioavailability and to Assess the Pharmacokinetic Profile, Safety and Tolerability of GSK933776 Administered by Subcutaneous or Intramuscular Injection Relative to Intravenous Administration to Healthy Volunteers

This study is intended to enable a possible transition to intramuscular (IM) or subcutaneous (SQ) administration for subsequent studies with GSK933776 by characterizing the safety, tolerability, PK and pharmacodynamic profiles, and immunogenicity of GSK933776 following IM and SQ administration in healthy volunteers. Such alternate routes of administration may provide more options in the selection of an efficacious dose for subsequent development in patients with geographic atrophy. There will be four treatment arms in the study and participants will be assigned to 1 of 4 possible treatment arms in a 1:1:1:1 ratio. The planned number of evaluable participants for this study is 24 with 6 participants completing all critical assessments in each of the four treatment arms. The total duration of participation from screening to follow-up for Treatment Arms A, B and D (single dose of GSK933776), will be approximately 113 days and total duration for Treatment Arm C (repeat dose of GSK933776) will be approximately 134 days.

Start Date22 Jan 2014

Sponsor / Collaborator

GSK Plc

[+1]

NCT01342926 / CompletedPhase 2

A Phase 2, Multi-centre, Randomised, Double-masked, Placebo-controlled, Parallel-group Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of GSK933776 in Adult Patients With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)

The purpose of this study is to determine the safety and efficacy of GSK933776 in the treatment of geographic atrophy secondary to age-related macular degeneration.

Start Date01 Jun 2011

Sponsor / Collaborator

GSK Plc

NCT01424436 / CompletedPhase 1

Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment

Modulation of beta-amyloid levels in CSF and plasma by GSK933776 in patients with mild Alzheimer's disease or mild cognitive impairment

Start Date19 May 2010

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-933776

100 Translational Medicine associated with GSK-933776

100 Patents (Medical) associated with GSK-933776

Literatures (Medical) associated with GSK-933776

01 Oct 2018·Ophthalmology. Retina

A Randomized Phase 2 Study of an Anti–Amyloid β Monoclonal Antibody in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Article

Author: Gress, Angie ; Berger, Brian ; McLaughlin, Megan M ; Reichel, Elias ; Rosenfeld, Philip J ; Danis, Ronald P ; Ye, Li ; Magee, Mindy ; Parham, Laura R

PURPOSE:

To investigate the efficacy of intravenous GSK933776, a humanized monoclonal antibody directed against the N-terminal amino acids of amyloid β, for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD).

DESIGN:

Prospective, randomized, placebo-controlled, double-masked, multicenter phase 2 clinical trial.

PARTICIPANTS:

Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.9 to 17 mm² were enrolled.

METHODS:

Participants were monitored monthly for 4 months during an observation period to determine the rate of GA enlargement in the study eye. After the observation period, randomization was performed into 1 of 4 treatment arms (GSK933776 at 3, 6, and 15 mg/kg/month and placebo). At each monthly visit over 18 months, participants underwent visual acuity testing under normal luminance and low-luminance conditions. Ocular imaging included color fundus photography, fundus autofluorescence, fluorescein angiography, and spectral-domain OCT.

MAIN OUTCOME MEASURE:

Enlargement in the area of GA measured from color fundus photographs with reference to fundus autofluorescence images.

RESULTS:

A total of 191 participants were randomized into the study, with 139 (73%) fulfilling the efficacy population criteria. Over 18 months, GSK933776 did not reduce the rate of GA enlargement relative to placebo. Overall, there were no consistent meaningful differences relative to placebo in any of the visual function measures. There was a correlation between the low-luminance visual acuity (LLVA) deficit at baseline and the rate of GA enlargement. Genetic variations in complement factor I (CFI) gene did not correlate with GA progression. No ocular serious adverse events considered related to the GSK933776 treatment were identified, and a similar number of nonocular serious adverse events were reported across all treatment groups.

CONCLUSIONS:

Intravenous amyloid β inhibition with GSK933776 did not slow the rate of GA enlargement compared with placebo, and no clinically meaningful differences relative to placebo were observed in visual function testing over 18 months. The LLVA deficit was associated with faster GA enlargement; however, no correlation was shown between genetic variations in the CFI gene and the rate of GA enlargement.

01 Sep 2015·European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VQ2 · MEDICINE

Antibody therapies and their challenges in the treatment of age-related macular degeneration

Q2 · MEDICINE

Review

Author: Volz, Cornelia ; Pauly, Diana

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world. This multifactorial disease results from the combined contributions of age, environment and genetic predisposition. Antibody-based treatment of late-stage neovascular AMD with inhibitors of vascular endothelial growth factor has had great success, which is now the goal for currently untreatable AMD manifestations. The existence of an immune-privileged environment in the eye supports the feasibility of localized antibody therapy. Many different antibodies against various targets are being developed for the treatment of AMD, which reflects the etiological complexity of the disease. This review provides an overview of 19 potential therapeutic antibodies targeting angiogenesis, the complement system, inflammation or amyloid beta deposition in the eye. It summarizes the immunoglobulin structure, the specific target and study outcomes for each approach. The latter include beneficial results or adverse effects in AMD models and patients. Finally, this article discusses the challenges in the development of antibody-based drugs to treat degenerative processes in the posterior eye. In spite of these difficulties, to date, the following four antibodies have overcome the technical and preclinical hurdles and are being tested in active clinical studies: Lampalizumab, Sonepcizumab, GSK933776 and LFG316. We conclude that, while there are some antibody-based drugs that have made it into clinical practice, a successful transfer from bench to beside is still pending for many promising approaches.

01 Jan 2014·Alzheimer's research & therapyQ2 · MEDICINE

Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study

Q2 · MEDICINE

ArticleOA

Author: Xin Tong ; Arno Reich ; Prafull Mistry ; Monica Simeoni ; Amy Loercher ; Charles Hottenstein ; Michelle Chalker ; Niels Andreasen ; Christine Af von Arnim ; Jan Hilpert ; Thomas Leyhe ; Shahid Khan ; Henrik Zetterberg ; Astrid Yeo

INTRODUCTION:

In this study, we evaluated the safety and pharmacodynamic effects of the Fc-inactivated anti-β-amyloid (anti-Aβ) monoclonal antibody GSK933776 in patients with mild Alzheimer's disease and mild cognitive impairment. Aβ and tau levels were investigated in cerebrospinal fluid (CSF), and the relationship between Aβ levels and Aβ modulation in plasma was explored. The feasibility of a continuous sampling method using a lumbar catheter was assessed.

METHODS:

This trial was a phase I, open-label, uncontrolled, single-dose, exploratory experimental medicine study of intravenous GSK933776 at doses of 1 mg/kg, 3 mg/kg or 6 mg/kg (n = 6/group). The time course of plasma and CSF concentrations of GSK933776 and Aβ was assessed. Sample size was based on feasibility, and no formal statistical analyses were performed.

RESULTS:

Following administration of GSK933776 at doses of 1 mg/kg, 3 mg/kg and 6 mg/kg, there were decreases from baseline in CSF Aβ1-42 (from 0 to 12 hours) by 22.8 pg/ml (6.2%), 43.5 pg/ml (9.2%) and 60.5 pg/ml (12.5%), respectively. Plasma concentrations of total Aβ18-35 and Aβ4228-42 increased immediately after infusion and CSF tau concentration increased slightly, but did not significantly change, following administration of all doses of GSK933776. Pharmacokinetics confirmed the presence of GSK933776 in the CSF, which exhibited a dose-response relationship. One patient underwent minor surgery without sequelae following a ruptured lumbar catheter.

CONCLUSION:

GSK933776 demonstrated pharmacological activity and target engagement in CSF and plasma, and the continuous sampling method via a catheter successfully assessed the Aβ changes following single-dose administration of GSK933776.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT01424436. Registered 4 August 2011.

News (Medical) associated with GSK-933776

04 Nov 2022

·www.prnewswire.com

Gates Biomanufacturing Facility Announces Manufacture of Recombinant Protein - Alzheimer's Disease Vaccine for Institute for Molecular Medicine's Clinical Trials

AURORA, Colo., Nov. 4, 2022 /PRNewswire/ -- The Gates Biomanufacturing Facility (GBF) has announced the successful completion of the full cycle manufacturing of the recombinant Bulk Drug Substance (BDS) of the anti-Tau vaccine, AV-1980R, in collaboration with the Institute for Molecular Medicine (IMM), California. Continue Reading Congresswoman Diana DeGette (D-CO) visits the Gates Biomanufacturing Facility's Protein Suite, in which GMP-grade AV-1980R was manufactured for the Institute for Molecular Medicine's phase 1 clinical trials. Vials of GMP-grade AV-1980R manufactured by the Gates Biomanufacturing Facility for Institute of Molecular Medicine's phase 1 Alzheimer's Disease Vaccine clinical trials IMM selected GBF as its exclusive cGMP-grade BDS manufacturing partner supporting clinical supply for IMM's recombinant protein vaccines, including AV-1980R. As a result of this work, AV-1980R Drug Substance can be used for phase 1 and phase 2 clinical trials in humans. This work was financed through funding provided by the U.S. National Institute on Aging (NIA). Abnormal Tau aggregation into neurofibrillary tangles is the hallmark of different tauopathies - neurodegenerative disorders that include Alzheimer's Disease (AD). Until now, AD therapeutics have mostly focused on the treatment of already diseased patients. AV-1980R vaccine targets Alzheimer's Disease (AD) and other Tau aggregation-associated neurodegenerative conditions by providing outstanding levels of antibody protection against harmful forms of Tau protein that may lead to disease. Dr. Michael Agadjanyan, Professor and Vice President of IMM commented, "But once pathology begins and neurons are damaged, it becomes impossible to stop the disease. Now, with the help of cGMP-grade AV-1980R manufactured by GBF, [IMM has] a highly immunogenic preventative vaccine that could induce significant levels of antibodies inhibiting aggregation of Tau in cognitively unimpaired people [who are] at risk of AD and halt the disease onset." Huntington Potter, PhD, Professor of Neurology, Director of Alzheimer's Disease Program at the Linda Crnic Institute for Down Syndrome, and Director of the CU Alzheimer's and Cognition Center at the University of Colorado Anschutz Medical Center maintains, "It is becoming increasingly clear that targeting Alzheimer amyloid deposits and their formation is not, alone, an effective approach to halting or reversing Alzheimer's disease. New therapeutics are needed. The development and manufacture of a Tau vaccine is one of the most promising approaches and might be used either alone or in combination with the anti-amyloid antibodies currently in clinical trials. I congratulate GBF on this important milestone." All vaccines developed by IMM are based on the proprietary MultiTEP platform technology, recently licensed to its commercial entity, Nuravax, which demonstrated therapeutic efficacy and immunogenicity in various species of transgenic animal models of AD, including non-human primates. ABOUT GBF The Charles C. Gates Center for Regenerative Medicine, in partnership with the University of Colorado School of Medicine, UCHealth University of Colorado Hospital, Children's Hospital Colorado, the Gates Frontiers Fund and the private sector have established a state-of-the-art Phase I GMP facility, which develops and manufactures investigational biologics and cell therapy products to support FDA-approved early phase clinical trials. 20,000 square feet of GMP-grade cleanrooms, laboratories, material storage are in the Fitzsimmons Innovation Zone just across the street from University of Colorado Anschutz Medical Campus research laboratories plus the adult and pediatric hospitals (). The facility currently produces therapeutic biologics; recombinant protein, nano-particle conjugate, nucleic acid-based therapeutics as well as CAR-T cells and other cell therapy products for clinical trials. The mission-based manufacturing facility serves academic researchers, clinicians, and early-stage biotechnology companies, focuses on translation of discoveries into clinical-grade products, and completes the medical ecosystem from basic research through early commercialization. ABOUT IMM The Institute for Molecular Medicine (IMM) is a non-profit organization created with the goal of understanding, preventing, and curing chronic human diseases, including neurodegenerative disorders. IMM works closely with its partner, Nuravax: a biotechnology company that licenses IMM's patented technology. Based in Orange County, California, IMM, along with Nuravax, is advancing MultiTEP: a universal vaccine platform technology that supports the development of multiple vaccine designs based on DNA, RNA, or recombinant proteins. Media Contact: Jill Cowperthwaite 303 564-8021 [email protected] SOURCE University of Colorado Anschutz Medical Campus

VaccineCollaborateAntibodyCell Therapy

08 Nov 2011

·www.biospace.com

Intellect Neurosciences, Inc. Obtains Two New Patents in Japan for Its Alzheimer's Immunotherapy Programs

NEW YORK, Nov. 8, 2011 /PRNewswire/ -- Intellect Neurosciences, Inc. (OTCBB: ILNS), a biopharmaceutical company engaged in the discovery and development of disease-modifying therapeutic agents for the treatment of Alzheimer's and other neurological diseases announces today that the Japanese Patent Office has granted the company two new patents for its Alzheimer's immunotherapy programs. Behind the United States, Japan is the second largest pharmaceutical market worldwide based on total revenue. "Building our intellectual property portfolio across the globe is an essential part of our overall business plan," commented Daniel Chain, Ph.D., Chairman and CEO of Intellect Neurosciences. "As we continue development of these technologies, through significant milestones in the near future, we anticipate continued interest in our pipeline from strategic partners and additional revenue-generating partnerships." One patent is for the company's RECALL-VAX technology and follows patents granted for that technology in Europe and the United States. The second is for IN-N01, which is already patented in the United States. The new immunotherapy patents expand the company's Japanese patent portfolio, which began in 2006 with its ANTISENILIN® Alzheimer's monoclonal antibody technology. RECALL-VAX is an active vaccine intended to generate highly specific antibodies against beta amyloid in serum of patients. The vaccine is a chimeric peptide comprised of a short human antigen B-cell neoepitope linked to a bacterial T-cell epitope such as Tetanus Toxoid against which most people have been previously vaccinated. The vaccine has therapeutic as well as prophylactic potential. Intellect is initiating further proof of concept studies in France to obtain multiple biomarker read-outs in transgenic models of Alzheimer's disease prior to commencing planned preclinical development work and ultimately testing in human clinical trials. IN-N01 is a proprietary product of the company's ANTISENILIN technology platform, which includes other products in development such as Bapineuzumab, which are being developed independently by major pharmaceutical companies. IN-N01 has similar specificity for the beta amyloid toxin as does Bapineuzumab. However, in contrast to Bapineuzumab, IN-N01 may have reduced risk of inflammation from immune responses in patients. In addition, IN-N01 is being developed as an antibody drug conjugate with OX2 under Intellect's new CONJUMAB-A platform technology. This combination is expected to increase clearance of beta amyloid from the brain as well as reduce inflammation, which can result in vasogenic edema, a side-effect of immunotherapy in some patients that result from antibody-mediated dissolution of plaque. The CONJUMAB-A platform for which IN-N01-OX2 is the flagship molecule, is applicable to a broad range of diseases including: Alzheimer's, Parkinson's, Huntington's, Age-Related Macular Degeneration, Glaucoma, Cerebral Angiopathy, Frontotemporal Dementia, Progressive Supranuclear Palsy, Pick's disease, Cortical Basal Degeneration and Peripheral Amyloidosis. About Intellect Neurosciences, Inc. Intellect Neurosciences, Inc. develops innovative approaches aimed at arresting or preventing Alzheimer's disease, and other neurodegenerative diseases especially focused on proteinopathies. Intellect's pipeline includes small neuroprotective molecules and neoepitope-based immunotherapy approaches including monoclonal antibodies and vaccines targeting beta amyloid and abnormal tau proteins. The company is currently developing three separate platform technologies: ANTISENILIN® is Intellect's Alzheimer's beta amyloid monoclonal antibody platform technology which underlies several products in advanced clinical development and is licensed to major pharmaceutical companies. The company's RECALL-VAX technology is a proprietary Alzheimer's vaccine with therapeutic and prophylactic potential. The company's CONJUMAB-A platform is based on antibody drug conjugates with potential applications to treat a broad spectrum of proteinopathies including Alzheimer's disease, Early-Onset Familial Alzheimer's disease, cerebral angiopathy, age-related macular degeneration, glaucoma and traumatic brain injury. IN-N01-OX2 is the company's most advanced internal candidate, a humanized monoclonal antibody targeting beta amyloid conjugated to a naturally occurring small drug molecule with potent neuroprotective properties. Thus, IN-N01-OX2, incorporates combined features of the ANTISENILIN and CONJUMAB-A platform technologies. The company recently licensed OX1 a small molecule multimodal antioxidant to ViroPharma, Inc. for Friedreich's Ataxia and other neurodegenerative diseases. Safe Harbor Statement Regarding Forward-Looking Statements: The statements in this release and oral statements made by representatives of Intellect relating to matters that are not historical facts (including, without limitation, those regarding future performance or financial results, the timing or potential outcomes of research collaborations or clinical trials, any market that might develop for any of Intellect's product candidates and the sufficiency of Intellect's cash and other capital resources) are forward-looking statements that involve risks and uncertainties, including, but not limited to, the likelihood that actual performance or results could materially differ, that future research will prove successful, the likelihood that any product in the research pipeline will receive regulatory approval in the United States or abroad, or Intellect's ability to fund such efforts with or without partners. Intellect undertakes no obligation to update any of these statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as to the date hereof. Accordingly, any forward-looking statements should be read in conjunction with the additional risks and uncertainties detailed in Intellect's filings with the Securities and Exchange Commission, including those factors discussed under the caption "Risk Factors" in Intellect's Annual Report on Form 10-K ( 333-128226), filed on October 13, 2011. Contact: Jules Abraham JQA Partners, LLC jabraham@jqapartners.com 917-885-7378 SOURCE Intellect Neurosciences, Inc.

VaccineFinancial StatementAntibodyImmunotherapySmall molecular drug

04 Dec 2007

·www.biospace.com

Japan's Eisai Company, Ltd. Buys Rights to Alzheimer's Antibody from BioArctic Neuroscience AB

Dec. 4 (Bloomberg) -- Eisai Co. bought the rights to an experimental Alzheimer's disease treatment from BioArctic Neuroscience AB, giving the Japanese drugmaker another potential successor to its best-seller, Aricept. Eisai, Japan's fourth-largest drugmaker, has the global rights to study, develop, manufacture and market the drug, known as BAN2401, under an agreement signed yesterday with Stockholm- based BioArctic Neuroscience. No financial terms were disclosed.

Antibody

100 Deals associated with GSK-933776

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Age Related Macular Degeneration	Phase 2	US	GSK Plc	01 Jun 2011
Age Related Macular Degeneration	Phase 2	CA	GSK Plc	01 Jun 2011
Geographic Atrophy	Phase 2	US	GSK Plc	01 Jun 2011
Geographic Atrophy	Phase 2	CA	GSK Plc	01 Jun 2011
Mild cognitive disorder	Phase 1	DE	GSK Plc	19 May 2010
Mild cognitive disorder	Phase 1	SE	GSK Plc	19 May 2010
Alzheimer Disease	Phase 1	AU	GSK Plc	12 Mar 2007
Alzheimer Disease	Phase 1	NO	GSK Plc	12 Mar 2007
Alzheimer Disease	Phase 1	SE	GSK Plc	12 Mar 2007

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01342926 (Pubmed) Manual	Phase 2	Age Related Macular Degeneration \| Geographic Atrophy	191	GSK 933776	ocpjmopbwj(oizrxquvbb) = Over 18 months, GSK933776 did not reduce the rate of GA enlargement relative to placebo. fmbbjlnfqe (mghrrbhpoq ) View more	Negative	01 Oct 2018
NCT01342926 (Pubmed) Manual	Phase 2	Age Related Macular Degeneration \| Geographic Atrophy	191	Placebo		Negative	01 Oct 2018
NCT01342926 (CTgov)	Phase 2	Age Related Macular Degeneration \| Geographic Atrophy	191	Placebo	ntkvtbsnmv(tzsjlhqlfc) = rdwtewqflg tcwiawdwkp (uygucgjtcv, acjffeliet - otctbnbesc) View more	-	05 May 2017

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