Alzheimer's DiseasePhase 1NCT00459550
A Clinical Study to Assess Single and Repeat Doses of a New Medication (GSK933776) in Patients With Alzheimer's Disease
A Phase 1 study testing GSK933776 in people with Alzheimer's Disease, run by GlaxoSmithKline at 7 sites in 3 countries.
Trial summary
A study to investigate the safety and tolerability of both single and multiple intravenous administration of GSK933776 in patients with Alzheimer's Disease. Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- GSK933776
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 12 Mar 2007to 30 May 2011
- Phase
- Phase 1
- 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 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject with a clinical diagnosis of probable Alzheimer's disease
- Subject has mild AD with Mini Mental State Examination (MMSE) score 18-26 inclusive at the screening visit.
- Age between 55 and 80 years.
- Female subjects must be post-menopausal or surgically sterile.
- Male subjects whose partner is of child-bearing potential or have been menopausal for <2 years must use an adequate form of contraception.
- Subject has the ability to comply with procedures for cognitive and other testing \& is fluent in the language used for the administration of the cognitive tests.
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- Subject lives with (or has substantial periods of contact with) a permanent caregiver who is willing to oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status.
- Subject has provided full written informed consent prior to the performance of any protocol-specified procedure.
- Caregiver has provided a full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.
Who cannot join
- History and/or evidence of any other central nervous system (CNS) disorder that could be interpreted as a cause of dementia.
- Subjects currently living in a nursing home.
- Subjects who are unable to provide informed consent due to cognitive status
- Screening brain MRI with 1 or more of the following conditions: not consistent with AD, evidence of other CNS conditions, shows more than minimal vascular changes, more than 3 microhaemorrhage lesions.
- Focal findings on the neurological exam.
- Any contraindication to lumbar puncture.
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- History or evidence of significant psychiatric illness such as schizophrenia or bipolar affective disorder or significant neurological disease other than AD.
- TIA/stroke in the last 3 years, type 1 or type 2 diabetes mellitus, active cardiovascular disease, or other uncontrolled risk factors for stroke.
- Current or recent drug or alcohol abuse or dependence or recent or remote history of the same if that could be a contributing factor to the dementia.
- History or evidence of any significant autoimmune disease or disorder.
- History of seizures (excluding febrile seizures in childhood), current blood clotting or bleeding disorder or conditions that predispose to these (e.g. cancer), current clinically significant systemic illness or significant infection within 30 days that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study.
- History of cerebral amyloid antiopathy and/or hypertensive cerebral haemorrhage or with a known risk of intercerebral haemorrhage/microhaemorrhage.
- Treatment which cholinesterase inhibitors, memantine or selegiline unless the therapy was instituted at least 3 months prior to the administration of GSK933776, at a stable dosage in the 2 months prior and the same regimen will be continued for the duration of the trial and the subject is free from any clinically significant side effects attributable to the drug.
- Subjects who have discontinued cholinesterase inhibitors, memantine, cognitive enhancing agents, or drugs that potentially affect cognition in the 60 days prior to screening.
- Unless maintained on a stable dose regimen for at least 30 days prior to screening, any other medications with the potential to affect cognition.
- Use of drugs with platelet anti-aggregant or anti-coagulant properties (excluding the use of aspirin 325 mg/day or less), anticonvulsants for seizures or narcotic medication.
- History of or current chronic use of systemic steroids or other immunosuppressants.
- Prior participation in clinical investigations involving therapeutic monoclonal antibodies or proteins derived from monoclonal antibodies or any investigations of treatments or use of experimental medications for AD or any other investigational medication or device within 60 days prior to screening or within 5 half-lives of use of such a medication prior to screening, whichever is longer.
- Contraindications for MRI: pacemaker, aneurysm clips, artificial heart valves, other metal foreign body, claustrophobia, etc.
- Smoking more than 20 cigarettes or equivalent per day.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Australia3 sites
GSK Investigational Site
Fremantle, Western Australia, 6160
GSK Investigational Site
Heidelberg Heights, Victoria, 3084
GSK Investigational Site
Herston, Queensland, 4029
Sweden3 sites
GSK Investigational Site
Malmö, SE-205 02
GSK Investigational Site
Mölndal, SE-431 41
GSK Investigational Site
Stockholm, se-141 86
About this study
Official title: A Randomised, Single-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Intravenous Infusion of GSK933776 in Patients With Alzheimer's Disease.
A study to investigate the safety and tolerability of both single and multiple intravenous administration of GSK933776 in patients with Alzheimer's Disease.
- Conditions
- Alzheimer's Disease
- Being tested
- GSK933776, Placebo to match GSK933776
- Keywords
- Alzheimer's Disease, First Time in Human (FTIH) Study
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK933776Drug
Also called GSK933776A
Part A planned doses cohort 1 to cohort 3 0.001 mg/kg, 0.01 mg/kg and 0.1 mg/kg.
Part B planned doses cohort 4 to cohort 7 0.1 mg/kg, 1mg/kg, 3mg/kg and 10 mg/kg
Placebo to match GSK933776Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: GSK933776; Drug: Placebo to match GSK933776 |
| 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 Receives: Drug: GSK933776; Drug: Placebo to match GSK933776 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs.
Measured: 12 weeks for Part A; 34 weeks in Part B
Secondary outcomes (1)
Plasma pharmacokinetic parameters of GSK933776. Pharmacodynamic effects of GSK 933776. CSF detectable levels of GSK933776. Effects of GSK933776 on plasma and CSF biomarkers. Titre & neutralising activity of anti-GSK933776 antibodies. Exploratory PET scan
Measured: 12 weeks for Part A; 34 weeks in Part B
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2007 (estimated)
- Study start12 Mar 2007
- Primary completion30 May 2011
- Study completion30 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00459550
- Sponsor's protocol ID
- 106006
- Status last verified
- Jul 2017
- First submitted
- 11 Apr 2007
- Last updated
- 21 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Andreasen N, Simeoni M, Ostlund H, Lisjo PI, Fladby T, Loercher AE, Byrne GJ, Murray F, Scott-Stevens PT, Wallin A, Zhang YY, Bronge LH, Zetterberg H, Nordberg AK, Yeo AJ, Khan SA, Hilpert J, Mistry PC. First administration of the Fc-attenuated anti-beta amyloid antibody GSK933776 to patients with mild Alzheimer's disease: a randomized, placebo-controlled study. PLoS One. 2015 Mar 19;10(3):e0098153. doi: 10.1371/journal.pone.0098153. eCollection 2015.
PubMed 25789616
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Single-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Intravenous Infusion of GSK933776 in Patients With Alzheimer's Disease.
- ClinicalTrials.gov ID
- NCT00459550
- Acronym / sponsor ID
- 106006
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's Disease, First Time in Human (FTIH) Study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 12 Mar 2007 (actual)
- Primary completion
- 30 May 2011 (actual)
- Study completion
- 30 May 2011 (actual)
- First posted
- 12 Apr 2007 (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.
A study to investigate the safety and tolerability of both single and multiple intravenous administration of GSK933776 in patients with Alzheimer's Disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A | Experimental | Drug: GSK933776, Drug: Placebo to match GSK933776Part 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 | Drug: GSK933776, Drug: Placebo to match GSK933776Part 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 |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subject with a clinical diagnosis of probable Alzheimer's disease
- Subject has mild AD with Mini Mental State Examination (MMSE) score 18-26 inclusive at the screening visit.
- Age between 55 and 80 years.
- Female subjects must be post-menopausal or surgically sterile.
- Male subjects whose partner is of child-bearing potential or have been menopausal for <2 years must use an adequate form of contraception.
Key exclusion criteria (20 listed)
- History and/or evidence of any other central nervous system (CNS) disorder that could be interpreted as a cause of dementia.
- Subjects currently living in a nursing home.
- Subjects who are unable to provide informed consent due to cognitive status
- Screening brain MRI with 1 or more of the following conditions: not consistent with AD, evidence of other CNS conditions, shows more than minimal vascular changes, more than 3 microhaemorrhage lesions.
- Focal findings on the neurological exam.
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 |
|---|---|---|
| GSK933776Also: GSK933776APart A planned doses cohort 1 to cohort 3 0.001 mg/kg, 0.01 mg/kg and 0.1 mg/kg. Part B planned doses cohort 4 to cohort 7 0.1 mg/kg, 1mg/kg, 3mg/kg and 10 mg/kg | Drug | Part A, Part B |
| Placebo to match GSK933776Part 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. | Drug | Part A, Part B |
Primary outcome
Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs.
Time frame: 12 weeks for Part A; 34 weeks in Part B
1 secondary outcome
Plasma pharmacokinetic parameters of GSK933776. Pharmacodynamic effects of GSK 933776. CSF detectable levels of GSK933776. Effects of GSK933776 on plasma and CSF biomarkers. Titre & neutralising activity of anti-GSK933776 antibodies. Exploratory PET scan
Time frame: 12 weeks for Part A; 34 weeks in Part B
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 21 Jul 2017.
- Derived from this study: PubMed 25789616Andreasen N, Simeoni M, Ostlund H, Lisjo PI, Fladby T, Loercher AE, Byrne GJ, Murray F, Scott-Stevens PT, Wallin A, Zhang YY, Bronge LH, Zetterberg H, Nordberg AK, Yeo AJ, Khan SA, Hilpert J, Mistry PC. First administration of the Fc-attenuated anti-beta amyloid antibody GSK933776 to patients with mild Alzheimer's disease: a randomized, placebo-controlled study. PLoS One. 2015 Mar 19;10(3):e0098153. doi: 10.1371/journal.pone.0098153. eCollection 2015.
- Results for study 106006 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK933776 in people with Alzheimer's Disease, run by GlaxoSmithKline at 7 sites in 3 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 9 inclusion and 20 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 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, Sweden, Norway. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Adverse events. Changes suggesting potential adverse events detected in the physical & neurological examination, brain MRI, cognitive status, laboratory parameters, ECG & vital signs. (time frame: 12 weeks for Part A; 34 weeks in Part B). 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 NCT00459550, which also lists 1 linked publication.
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 21 Jul 2017.