First Time in Human Study of GSK1223249 in Amyotrophic Lateral Sclerosis

NCT00875446 | Completed Phase 1

• 1 other identifier: 111330
• Study Type: interventional
• Target: 76
• Locations: 4 countries
• Sites: 12

Brief 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. 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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  12-16 Weeks

• Presence of antibodies to GSK1223249 will be assessed in serum samples using immuno-electrochemiluminescent assay.

  At least 16 weeks

• ALSFRS-R scores, Manual Muscle Strength test and Slow Inspirational Vital Capacity (SVC)

  12-16Weeks

• Motor Unit Number Estimation (MUNE)

  12-16 Weeks

• Muscle biopsies for protein analysis, Immunohistochemistry (IHC), Transcriptomics. Blood for protein analysis and other biomarkers.

  At least 16 weeks

Study Arms (2)

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.

Drug: GSK1223249

Subjects receiving placebo

PLACEBO COMPARATOR

Eligible subjects will receive intravenous infusion of placebo.

Drug: PLACEBO

Interventions

PLACEBO DRUG

Placebo

Subjects receiving placebo

GSK1223249 DRUG

I.V Infusion

Subjects receiving GSK1223249

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• 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 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
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Baltimore, Maryland, 21287, United States

Location

GSK Investigational Site

New York, New York, NY 10021, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Charlotte, North Carolina, NC 28207-1885, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27157, United States

Location

GSK Investigational Site

Columbus, Ohio, OH 43210, United States

Location

GSK Investigational Site

Paris, 75013, France

Location

GSK Investigational Site

Verona, Veneto, 37134, Italy

Location

GSK Investigational Site

Birmingham, B15 2TH, United Kingdom

Location

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

GSK Investigational Site

London, NW3 2PF, United Kingdom

Location

GSK Investigational Site

London, SE5 8AF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24841795 DERIVED

Related Links

• Results for study 111330 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ozanezumab

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2009
• First Posted: April 3, 2009
• Study Start: May 13, 2009
• Primary Completion: September 9, 2011
• Study Completion: September 9, 2011
• Last Updated: September 20, 2017

Record last verified: 2017-09

Locations

IT (1); FR (1); GB (4); US (6)