Amyotrophic Lateral SclerosisPhase 1NCT00875446
First Time in Human Study of GSK1223249 in Amyotrophic Lateral Sclerosis
A Phase 1 study testing GSK1223249 in people with Amyotrophic Lateral Sclerosis, run by GlaxoSmithKline at 12 sites in 4 countries.
Trial summary
The drug being tested in this study is GSK1223249. It is being developed by GlaxoSmithKline to treat symptoms in patients with Amyotrophic Lateral Sclerosis (ALS). The drug works by inhibiting the protein that prevents nerve growth. This will be the first time the drug will be given to man. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- GSK1223249
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 13 May 2009to 9 Sep 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the revised World Federation of Neurology El Escorial criteria [Rix Brooks 2000].
- Onset of muscle weakness within 60 months of study entry.
- Patients who have low Slow Inspiratory Vital Capacity (SVC) below that what is predicted for age and sex can be included into the study at the discretion of the investigator as long as they are NOT respiratory insufficient.
- If on any medication (including riluzole), these must have been stable within the previous one month. (See also 'Concomitant Medications' - Section 8).
- Age 18 - 80 years inclusive.
- Male or Female of non-childbearing potential (NCBP) defined as follows:
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- Pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and oestradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 7.1.1, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Male subjects must agree to use one of the contraception methods listed in Section 7.1.2. This criterion must be followed from the time of the first dose of study medication until the last follow-up visit.
- QTcB < 500 msec or uncorrected QT <600msec (machine or manual overread). If subject has bundle branch block then criteria is QTcB < 530 msec.
- A Body Mass Index that at the discretion of the investigator is acceptable for inclusion into the study.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- Patients with other neuromuscular disorders (in addition to their ALS diagnosis), unless the investigator determines that such additional disorder will not affect safety or other measures in this study.
- Patients with evidence of dementia or psychiatric illness which, in the investigator's opinion, is likely to prevent them from a full understanding of and/or compliance with the study requirements and procedures.
- Patients with abnormalities detected during the screening evaluations which, in the investigator's medical judgement, are sufficiently significant to exclude them from participation in the study.
- Patients who have participated in a clinical trial involving receipt of a biopharmaceutical product within 6 months prior to the first dosing day.
- Exposure to more than four new investigational products within 12 months prior to the first dosing day.
- The subject has a positive drugs of abuse test at the screening or pre dose visit. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates and benzodiazepines. Subjects who are on any of these drugs by prescription for medical reasons may be considered by the investigator for inclusion if they fulfil other entry criteria.
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- The subject has a positive alcohol test at the pre-dose visit. History of regular excessive alcohol consumption within 6 months of the study defined as:
- For European sites: an average weekly intake of > 28 units for males or >21 units for females. One unit is equivalent to 8g of alcohol: a half-pint (~240mL) of beer, 1 glass (125mL) of wine or 1 (25mL) measure of spirits.
- For North American sites: an average weekly intake of >21 drinks for males or >14 drinks for women. One drink is equivalent to 12 g alcohol: 12 ounces (360mL) of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
- History of sensitivity to GSK1223249, or components thereof, or a history of drugs or other allergies that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Females of childbearing potential, pregnant females as determined by positive serum or urine beta hCG test at screening or prior to dosing, or lactating females.
- Patients who have received any type of vaccination in the last 3 weeks before study drug administration.
- Unwillingness or inability to follow the procedures outlined in the protocol
- Subjects who will undergo muscle biopsies (cohorts 3-optional 5, 6, 7 and 8 will not be eligible for inclusion, if any of the following criteria apply:
- Patients with wasted deltoids (MRC score ≤ 2) and patients with normal deltoids (MRC score 5).
- Patients who cannot achieve normal coagulation in the peri-operative period and those who may otherwise be at higher risk of bleeding complications
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
United States6 sites
GSK Investigational Site
Baltimore, Maryland, 21287
GSK Investigational Site
Charlotte, North Carolina, NC 28207-1885
GSK Investigational Site
Columbus, Ohio, OH 43210
GSK Investigational Site
New York, New York, NY 10021
GSK Investigational Site
Syracuse, New York, 13210
GSK Investigational Site
Winston-Salem, North Carolina, 27157
United Kingdom4 sites
GSK Investigational Site
Birmingham, B15 2TH
GSK Investigational Site
Cambridge, CB2 2GG
GSK Investigational Site
London, NW3 2PF
GSK Investigational Site
London, SE5 8AF
About this study
Official title: A Single and Repeat Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of GSK1223249 in ALS Patients
The drug being tested in this study is GSK1223249. It is being developed by GlaxoSmithKline to treat symptoms in patients with Amyotrophic Lateral Sclerosis (ALS).
The drug works by inhibiting the protein that prevents nerve growth.
This will be the first time the drug will be given to man. The trial is expected to involve approximately 76 patients. The study objective is to investigate the tolerability, safety and the way the body handles GSK1223249 after a range of single doses or repeat dose escalation in patients with ALS.
Read the detailed description
This is the first-time-in-human (FTIH) phase I/IIa study of GSK1223249, a humanised monoclonal antibody against Nogo-A, a neurite outgrowth inhibitor hypothesised to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS) and some other neurodegenerative disorders. This study will be a randomized, placebo-controlled, double-blind, sequential dose escalation, 2-part fusion protocol. Approximately 76 patients with ALS will be enrolled. In Part 1, single escalating intravenous (i.v.) doses of GSK1223249 are planned to be evaluated in 5 sequential patient cohorts (2 placebo and 6 active in each cohort) to determine single dose safety and pharmacokinetics (PK). Part 2 will also be of a sequential dose escalating design, but patients in each of the planned 3 cohorts (3 placebo, 9 active in each cohort) will receive 2 repeat i.v. doses approximately 4 weeks apart where, safety and PK will also be evaluated. In two cohorts in Part 1 and all cohorts in Part 2, blood samples and skeletal muscle biopsies will be taken from patients before and at the end of treatment to demonstrate whether or not GSK1223249 binds to its target and produces any measurable pharmacodynamic effect. Patients in both parts will receive their first dose in a hospital-based unit where they will be monitored for at least 24 hours post-dose before being discharged to be followed on an out-patient basis. In each cohort in part 1, the first four subjects will be dosed in a staggered manner such that only one will receive the dose in any 24 hours. Dosing of the first four subjects in the first cohort of part 2 will also be staggered in a similar manner.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- PLACEBO, GSK1223249
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLACEBODrug
Placebo
GSK1223249Drug
I.V Infusion
| Study group | Role | What they receive |
|---|---|---|
| Subjects receiving GSK1223249 | Experimental | Eligible subjects will receive sequential dose of intravenous infusion of GSK1223249 with a starting dose of 0.01 milligram per kilogram followed by 0.1, 0.5,
1, 2.5, 5, 7.5, and 15 milligrams per kilograms. Receives: Drug: GSK1223249 |
| Subjects receiving placebo | Placebo comparator | Eligible subjects will receive intravenous infusion of placebo. Receives: Drug: PLACEBO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events, vital signs, standard physical examination, ECG and standard clinical laboratory tests (haematology and biochemistry). Evaluation of safety will include any adverse effects on Immunogenicity, ALSFRS-R, SVC, Muscle Strength and MUNE.
Measured: 12-16 Weeks
Secondary outcomes (6)
GSK1223249: Single dose PK (Part 1): AUC(0-∞), AUC(0-t), AUC(0-Week 4), %AUCex, Cmax, tlast, CL, Vss, MRT, λz and t½.Repeat dose PK (Part 2): GSK1223249 AUC(0-Week 4), Cmax and after the second dose, AUC(0-t), AUC(0-∞),λz and t½.
Measured: 12-16 Weeks
Presence of antibodies to GSK1223249 will be assessed in serum samples using immuno-electrochemiluminescent assay.
Measured: At least 16 weeks
ALSFRS-R scores, Manual Muscle Strength test and Slow Inspirational Vital Capacity (SVC)
Measured: 12-16Weeks
Motor Unit Number Estimation (MUNE)
Measured: 12-16 Weeks
Muscle biopsies for protein analysis, Immunohistochemistry (IHC), Transcriptomics. Blood for protein analysis and other biomarkers.
Measured: At least 16 weeks
Relationships between PK of GSK1223249 and relevant pharmacological endpoints
Measured: At least 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2009 (estimated)
- Study start13 May 2009
- Primary completion9 Sep 2011
- Study completion9 Sep 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 Amyotrophic Lateral SclerosisStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 76 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
- NCT00875446
- Sponsor's protocol ID
- 111330
- Status last verified
- Sep 2017
- First submitted
- 2 Apr 2009
- Last updated
- 20 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Meininger V, Pradat PF, Corse A, Al-Sarraj S, Rix Brooks B, Caress JB, Cudkowicz M, Kolb SJ, Lange D, Leigh PN, Meyer T, Milleri S, Morrison KE, Orrell RW, Peters G, Rothstein JD, Shefner J, Lavrov A, Williams N, Overend P, Price J, Bates S, Bullman J, Krull D, Berges A, Abila B, Meno-Tetang G, Wurthner J. Safety, pharmacokinetic, and functional effects of the nogo-a monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial. PLoS One. 2014 May 19;9(5):e97803. doi: 10.1371/journal.pone.0097803. eCollection 2014.
PubMed 24841795
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single and Repeat Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of GSK1223249 in ALS Patients
- ClinicalTrials.gov ID
- NCT00875446
- Acronym / sponsor ID
- 111330
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 13 May 2009 (actual)
- Primary completion
- 9 Sep 2011 (actual)
- Study completion
- 9 Sep 2011 (actual)
- First posted
- 3 Apr 2009 (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.
The drug being tested in this study is GSK1223249. It is being developed by GlaxoSmithKline to treat symptoms in patients with Amyotrophic Lateral Sclerosis (ALS).
The drug works by inhibiting the protein that prevents nerve growth.
This will be the first time the drug will be given to man. The trial is expected to involve approximately 76 patients. The study objective is to investigate the tolerability, safety and the way the body handles GSK1223249 after a range of single doses or repeat dose escalation in patients with ALS.
Detailed description
This is the first-time-in-human (FTIH) phase I/IIa study of GSK1223249, a humanised monoclonal antibody against Nogo-A, a neurite outgrowth inhibitor hypothesised to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS) and some other neurodegenerative disorders. This study will be a randomized, placebo-controlled, double-blind, sequential dose escalation, 2-part fusion protocol. Approximately 76 patients with ALS will be enrolled. In Part 1, single escalating intravenous (i.v.) doses of GSK1223249 are planned to be evaluated in 5 sequential patient cohorts (2 placebo and 6 active in each cohort) to determine single dose safety and pharmacokinetics (PK). Part 2 will also be of a sequential dose escalating design, but patients in each of the planned 3 cohorts (3 placebo, 9 active in each cohort) will receive 2 repeat i.v. doses approximately 4 weeks apart where, safety and PK will also be evaluated. In two cohorts in Part 1 and all cohorts in Part 2, blood samples and skeletal muscle biopsies will be taken from patients before and at the end of treatment to demonstrate whether or not GSK1223249 binds to its target and produces any measurable pharmacodynamic effect. Patients in both parts will receive their first dose in a hospital-based unit where they will be monitored for at least 24 hours post-dose before being discharged to be followed on an out-patient basis. In each cohort in part 1, the first four subjects will be dosed in a staggered manner such that only one will receive the dose in any 24 hours. Dosing of the first four subjects in the first cohort of part 2 will also be staggered in a similar manner.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving GSK1223249 | Experimental | Drug: GSK1223249Eligible subjects will receive sequential dose of intravenous infusion of GSK1223249 with a starting dose of 0.01 milligram per kilogram followed by 0.1, 0.5, 1, 2.5, 5, 7.5, and 15 milligrams per kilograms. |
| Subjects receiving placebo | Placebo comparator | Drug: PLACEBOEligible subjects will receive intravenous infusion of placebo. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the revised World Federation of Neurology El Escorial criteria [Rix Brooks 2000].
- Onset of muscle weakness within 60 months of study entry.
- Patients who have low Slow Inspiratory Vital Capacity (SVC) below that what is predicted for age and sex can be included into the study at the discretion of the investigator as long as they are NOT respiratory insufficient.
- If on any medication (including riluzole), these must have been stable within the previous one month. (See also 'Concomitant Medications' - Section 8).
- Age 18 - 80 years inclusive.
Key exclusion criteria (17 listed)
- Patients with other neuromuscular disorders (in addition to their ALS diagnosis), unless the investigator determines that such additional disorder will not affect safety or other measures in this study.
- Patients with evidence of dementia or psychiatric illness which, in the investigator's opinion, is likely to prevent them from a full understanding of and/or compliance with the study requirements and procedures.
- Patients with abnormalities detected during the screening evaluations which, in the investigator's medical judgement, are sufficiently significant to exclude them from participation in the study.
- Patients who have participated in a clinical trial involving receipt of a biopharmaceutical product within 6 months prior to the first dosing day.
- Exposure to more than four new investigational products within 12 months prior to the first dosing day.
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 |
|---|---|---|
| PLACEBOPlacebo | Drug | Subjects receiving placebo |
| GSK1223249I.V Infusion | Drug | Subjects receiving GSK1223249 |
Primary outcome
Adverse events, vital signs, standard physical examination, ECG and standard clinical laboratory tests (haematology and biochemistry). Evaluation of safety will include any adverse effects on Immunogenicity, ALSFRS-R, SVC, Muscle Strength and MUNE.
Time frame: 12-16 Weeks
6 secondary outcomes
GSK1223249: Single dose PK (Part 1): AUC(0-∞), AUC(0-t), AUC(0-Week 4), %AUCex, Cmax, tlast, CL, Vss, MRT, λz and t½.Repeat dose PK (Part 2): GSK1223249 AUC(0-Week 4), Cmax and after the second dose, AUC(0-t), AUC(0-∞),λz and t½.
Time frame: 12-16 Weeks
Presence of antibodies to GSK1223249 will be assessed in serum samples using immuno-electrochemiluminescent assay.
Time frame: At least 16 weeks
ALSFRS-R scores, Manual Muscle Strength test and Slow Inspirational Vital Capacity (SVC)
Time frame: 12-16Weeks
Motor Unit Number Estimation (MUNE)
Time frame: 12-16 Weeks
Muscle biopsies for protein analysis, Immunohistochemistry (IHC), Transcriptomics. Blood for protein analysis and other biomarkers.
Time frame: At least 16 weeks
Relationships between PK of GSK1223249 and relevant pharmacological endpoints
Time frame: At least 16 weeks
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 20 Sep 2017.
- Derived from this study: PubMed 24841795Meininger V, Pradat PF, Corse A, Al-Sarraj S, Rix Brooks B, Caress JB, Cudkowicz M, Kolb SJ, Lange D, Leigh PN, Meyer T, Milleri S, Morrison KE, Orrell RW, Peters G, Rothstein JD, Shefner J, Lavrov A, Williams N, Overend P, Price J, Bates S, Bullman J, Krull D, Berges A, Abila B, Meno-Tetang G, Wurthner J. Safety, pharmacokinetic, and functional effects of the nogo-a monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial. PLoS One. 2014 May 19;9(5):e97803. doi: 10.1371/journal.pone.0097803. eCollection 2014.
- Results for study 111330 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1223249 in people with Amyotrophic Lateral Sclerosis, run by GlaxoSmithKline at 12 sites in 4 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 11 inclusion and 17 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 20 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, United Kingdom, France, Italy. 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. Some participants in this study may receive a placebo. 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, vital signs, standard physical examination, ECG and standard clinical laboratory tests (haematology and biochemistry). Evaluation of safety will include any adverse effects on Immunogenicity, ALSFRS-R, SVC, Muscle Strength and MUNE. (time frame: 12-16 Weeks). 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 NCT00875446, 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 20 Sep 2017.