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Also known as GSK933776A
GSK933776 · 3 trials · 2 indications
Atrophic age-related macular degeneration (AMD) also called GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by color FP at the indicated time points: screening, 6 months, 12 months and 18 months. Change from BL: (screening, month 6, 12 or 18 value minus BL value. Note screening occurs prior to BL). Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Efficacy Population: all participants in the Intent-to-Treat (ITT) Population who met the protocol defined inclusion criterion for area of GA assessed by color FP in the study eye in at least one visit from screening visit through BL visit, inclusive and had data of area of GA assessed by fundus autofluorescence images in the study eye for at least 75% of the visits (\>=14 visits) from post-BL treatment month 2 visit to treatment month 19 visit.
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It includes:1. Any abnormal laboratory test results or other safety assessments including those that worsen from Baseline, and felt to be clinically significant in the medical and scientific judgment of the Investigator 2.Exacerbation (increase in frequency/intensity) of a chronic or intermittent pre-existing condition 3. New conditions detected or diagnosed after screening visit 4. Signs, symptoms, or the clinical sequelae of a suspected interaction/suspected overdose of investigational product or a concomitant medication. AEs were presented as non-ocular and ocular AEs.
Vital signs included SBP and DBP of Potential Clinical Importance (PCI) at the indicated time points: Baseline, month 0, month 1, month 2, month 3, month 4, month 5, month 6, month 7, month 8, month 9, month 10, month 11, month 12, month 13, month 14, month 15, month 16, month 17, month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. SBP was defined as: low: \<85 millimeter of mercury (mmHg) and high: \>160 mmHg and DBP was defined as: low:\<45 mmHg and high: \>100 mmHg. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Vital signs included HR of CCR at the indicated time points: Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. HR was defined as: low:\< 40 beats per minute (bpm) and high: \>100 bpm. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
12-lead ECG was obtained after 10 minutes rest in a supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Abnormal-clinically significant (CS) ECG measurements are presented at indicated time points: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
The following laboratory parameters were assessed: Hematology: Platelet Count, Red Blood Cell Count, White Blood Cell (WBC) Count, Reticulocyte Count, Hemoglobin, Hematocrit, Prothrombin time-International Normalized Ratio, Activated partial thromboplastin time, Mean corpuscular volume, Mean corpuscular haemoglobin, Mean corpuscular hemoglobin concentration, Neutrophils (ANC), Lymphocytes, Monocytes, Eosinophils, and Basophils. Clinical chemistry: Blood urea nitrogen, Potassium, Aspartate aminotransferase, Total and direct bilirubin Creatinine, Chloride, Alanine aminotransferase, Uric Acid, Glucose (fasting), Total Carbon dioxide , Gamma glutamyltransferase, Albumin, Sodium, Calcium, Alkaline phosphatase, Total Protein, and HbA1c. Urine: Specific gravity, pH, glucose, protein, blood and ketones and Microscopic examination. Only those with PCIs are displayed.
Magnetic Resonance Imaging (MRI) was used as a safety assessment to monitor for amyloid related imaging abnormalities (ARIA) events in the brain. MRIs were performed at Baseline and before dose 2, before dose 3, before dose 4, before dose 6, before dose 12, before dose 18 and at follow-up. ARIA-edema/effusions (ARIA-E) and ARIA hemosiderin deposition (ARIA-H) events at any visit are reported.
To compare the changes of amyloid beta levels between the baseline (9 hours) and after single dose of GSK933776 iv administration of 13 hours
| Arm | Type | Description |
|---|---|---|
| GSK933776 3 mg/kg | EXPERIMENTAL | 3 mg/kg administration of GSK933776 via intravenous infusion |
| GSK933776 6 mg/kg | EXPERIMENTAL | 6 mg/kg administration of GSK933776 via intravenous infusion |
| Placebo | PLACEBO_COMPARATOR | Placebo via intravenous infusion |
| GSK933776 15 mg/kg | EXPERIMENTAL | 15 mg/kg administration of GSK933776 via intravenous infusion |
| GSK933776 1mg/kg | EXPERIMENTAL | single dose |
| GSK933776 0.1 or 3mg/kg | EXPERIMENTAL | single dose |
| GSK933776 3 or 6mg/kg | EXPERIMENTAL | single dose |
| Part A | EXPERIMENTAL | Part A will be a single-blind, single dose, placebo controlled, dose escalation study in up to five consecutive cohorts of Alzheimers Disease subjects. Each subject will receive a single infusion of GSK933776 or placebo. The dose for the first cohort will be 0.001 mg/kg. The proposed nominal doses for subsequent cohorts are 0.01, 0.1, 0.5 and 3 mg/kg, but these may be altered based on the outcome of the safety, tolerability, pharmacodynamic and pharmacokinetic data of the preceding group(s). The maximum possible dose will be 20 mg/kg, although the planned top dose is 18 mg/kg |
| Part B | EXPERIMENTAL | Part B will be a single-blind, repeat dose, placebo controlled dose escalation design. It is proposed that there will be initially 3 cohorts of AD subjects. However up to 5 cohorts may be recruited if required in order to characterise GSK933776 fully.Each cohort will consist of eight subjects (six active, two placebo) who will each receive a maximum of three infusions of GSK933776 or placebo. Dosing in Part B may proceed in parallel with Part A following satisfactory review of minimum data sets as below: First cohort in Part B: at least 3 weeks' data from the Part A dose that is the same dose level as that planned for Part B Second cohort in Part B: at least 3 weeks PK data and 8 weeks safety data following the first dose from all the subjects on active treatment in the preceding Part B cohort plus a satisfactory outcome of the PIB Subsequent cohorts in Part B: at least 3 weeks PK data and 8 weeks safety data follow |
| Name | Type | Description |
|---|---|---|
| GSK933776 | DRUG | GSK933776 |
| Placebo | DRUG | Placebo |
| Placebo to match GSK933776 | DRUG | Part A first 2 cohorts 5 patients per cohort 2 placebo and 3 active third cohort part A 2 placebo 6 active. Part B 8 patients per cohort 2 placebo 6 active. |
Inclusion Criteria: * Adult patients ≥55 years of age inclusive * Evidence of AMD confirmed by the presence of at least 1 druse ≥125 μm diameter * Well-demarcated GA due to AMD of total area 1.9-17 mm2 measured in the study eye * Best-corrected visual acuity score of ≥ 35 letters (approximately 20/...
GSK933776 is an investigational small molecule developed by GSK plc for neurological conditions. It has been studied in Alzheimer's disease and in geographic atrophy secondary to age-related macular degeneration. It is not an approved therapy and remains in clinical development.
GSK933776 has been studied for Alzheimer's disease and for geographic atrophy secondary to age-related macular degeneration. Both are neurological and ophthalmic conditions affecting older adults. The clinical program enrolled patients aged 55 years and older in trials conducted across Europe and North America.
GSK933776 targets amyloid precursor protein, or APP, acting as a binding agent. APP is the precursor protein from which amyloid beta peptides are generated, and the compound was designed to modulate amyloid beta levels. One Phase 1 trial was titled Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient.
GSK933776 is developed by GSK plc, which trades under the ticker GSK. The company sponsored the clinical trials evaluating the compound in Alzheimer's disease and geographic atrophy.
GSK933776 is in Phase 1 development. It is an investigational agent and has not been approved by the FDA. Its clinical trials have been completed, and no trials are currently active.
GSK933776 has been evaluated in completed trials including NCT01424436, a Phase 1 study in Alzheimer's disease patients in Germany and Sweden; NCT01342926, a Phase 2 study in geographic atrophy in the United States and Canada; and NCT00459550, a Phase 1 study in Alzheimer's disease patients in Australia, Norway, and Sweden.