Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy
A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy
1 other identifier
interventional
313
6 countries
48
Brief Summary
The purpose of the study is to evaluate the safety and efficacy of davunetide for the treatment of Progressive Supranuclear Palsy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2010
48 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 23, 2010
CompletedFirst Posted
Study publicly available on registry
April 27, 2010
CompletedStudy Start
First participant enrolled
October 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedJanuary 17, 2013
January 1, 2013
2.1 years
April 23, 2010
January 15, 2013
Conditions
Outcome Measures
Primary Outcomes (3)
Efficacy, as measured by change from baseline scores of the Progressive Supranuclear Palsy Rating Scale (PSPRS) at 52 weeks
52 weeks
Efficacy, as measured by the change from baseline of the Schwab and England Activities of Daily Living Scale (SEADL) at 52 weeks
52 weeks
Safety, as measured by reported AEs, electrocardiograms (ECG), nasal examinations and clinical laboratory measures
52 weeks
Secondary Outcomes (2)
Efficacy, as measured by the Clinical Global Impression of Change (CGI-C) at 52 weeks
52 weeks
Brain atrophy, as measured by change from baseline of ventricular volumes measured by volumetric brain MRI at 52 weeks.
52 weeks
Study Arms (2)
Davunetide 30 mg BID
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Probable or possible PSP defined as:
- at least a 12-month history of postural instability or falls during the first 3 years that symptoms are present; and
- at screening, a decreased downward saccade velocity defined as observable eye movement (deviation from the "main sequence" linear relationship between saccade amplitude and saccade velocity) or, supranuclear ophthalmoplegia defined as 50% reduction in upward gaze or 30% reduction in downward gaze; and
- age at symptom onset of 40 to 85 years by history; and
- an akinetic-rigid syndrome with prominent axial rigidity.
- Aged 41 to 85 years at the time of screening.
- Judged by investigator to be able to comply with neuropsychological evaluation at baseline and throughout the study.
- Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand, and speak local language fluently to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 hours per week at one time or at different times) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
- Modified Hachinski score ≤ 3 (Appendix 7). This modified Hachinski will not include the focal neurological signs, symptoms or pseudobulbar affect questions, given the prominence of all 3 in PSP.
- Score ≥ 15 on the mini-mental state examination (MMSE) at screening (Visit 1).
- Written informed consent provided by subject (or legally-appointed representative, as appropriate) and caregiver (if not the legally-appointed representative) who are both fluent local language speakers.
- Subject resides outside a skilled nursing facility or dementia care facility at the time of screening, and admission to such a facility is not planned. Residence in an assisted living facility is allowed.
- If the subject is receiving levodopa/carbidopa, levodopa/benserazide, a dopamine agonist, catechol-o-methyltransferase (COMT) inhibitor, or other Parkinson's medication,with teh exception of Azilect(rasagiline), the dose must have been stable for at least 60 days prior to the screening visit (Visit 1) and must remain stable for the duration of the study. No such medication can be initiated during the study. Subjects receiving rasagiline or CoQ10 must be on a stable dose for at least 90 days prior to the screening visit.
- Able to tolerate the MRI scan during screening with either no sedation or low dose lorazepam.
- Able to ambulate independently or with assistance defined as the ability to take at least 5 steps with a walker (guarding is allowed provided there is no contact) or the ability to take at least 5 steps with the assistance of another person who can only have contact with one upper extremity.
- +2 more criteria
You may not qualify if:
- Insufficient fluency in local language to complete neuropsychological and functional assessments.
- A diagnosis of Amyotrophic Lateral Sclerosis or other motor neuron disease.
- Any of the following:
- Cerebellar ataxia,
- Choreoathetosis,
- Early, symptomatic autonomic dysfunction; or
- Tremor while at rest.
- Presence of other significant neurological or psychiatric disorders including (but not limited to) Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease (which has not subsequently been revised to PSP); any psychotic disorder; severe bipolar or unipolar depression; seizure disorder; tumor or other space-occupying lesion; or history of stroke or head injury with loss of consciousness for at least 15 minutes within the past 20 years.
- Within 4 weeks of screening or during the course of the study, concurrent treatment with memantine; acetylcholinesterase inhibitors; antipsychotic agents (other than quetiapine) or mood stabilizers (e.g., valproate, lithium); or benzodiazepines (except as below).
- Low dose lorazepam (not more than 2 mg) may be used for sedation prior to MRI scans for those subjects requiring sedation. Neuropsychological testing may not be performed after lorazepam administration.
- Subjects who take short acting benzodiazepines (only temazepam or zolpidem are allowed) for sleep may continue to do so if they have been on a stable dose for 30 days prior to screening.
- Clonazepam may be used for treatment of dystonia or painful rigidity associated with PSP if the dose has been stable for 90 days prior to screening and is not expected to change during the course of the study.
- Treatment with lithium, methylene blue, tramiprosate, ketone bodies, latrepirdine, or any putative disease-modifying agent directed at tau within 90 days of screening.
- A history of alcohol or substance abuse within 1 year prior to screening and deemed to be clinically significant by the site investigator.
- Any malignancy (other than non-metastatic dermatological conditions) within 5 years of the screening visit (Visit 1) or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. For the non-cancer conditions, if the condition has been stable for at least one year before the screening visit and is judged by the site investigator not to interfere with the subject's participation in the study, the subject may be included.
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (48)
University of Alabama - Birmingham
Birmingham, Alabama, 35294, United States
Muhammed Ali Parkinson Center and Movement Disorders Clinic
Phoenix, Arizona, 85013, United States
Mayo Clinic, AZ
Scottsdale, Arizona, 85259, United States
USC Keck School of Medicine
Los Angeles, California, 90033, United States
David Geffen School of Medicine - UCLA
Los Angeles, California, 90095, United States
UCSD/VA Neurology Service
San Diego, California, 92161, United States
UCSF Memory and Aging Center
San Francisco, California, 94143, United States
Colorado Neurological Institute - Rocky Mountain Movement Disorders Ctr, PC
Englewood, Colorado, 80113, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486, United States
Mayo Clinic, Florida
Jacksonville, Florida, 32224, United States
The Frances J. Zesiewicz Foundation for Parkinson's Disease at USF
Tampa, Florida, 33612, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
University of Kansas Medical Center Parkinson Disease & Movement Disorders Center
Kansas City, Kansas, 66160, United States
University of Louisville Division of Movement Disorders
Louisville, Kentucky, 40202, United States
John Hopkins Hospital
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02115, United States
Lahey Clinic
Burlington, Massachusetts, 01805, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
University of Minnesota Department of Neuology
Minneapolis, Minnesota, 55455, United States
Mayo Clinic, Rochester, MN
Rochester, Minnesota, 55905, United States
UMDNJ - Robert Wood Johnson Medical Center
New Brunswick, New Jersey, 08901, United States
Columbia University
New York, New York, 10032, United States
Univeristy of North Carolina Department of Neurology
Chapel Hill, North Carolina, 27599, United States
University Hospitals Case Medical CenterNI Movement Disorders Center
South Euclid, Ohio, 44121, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Utah Center for Alzheimer's Care, Imaging &Research
Salt Lake City, Utah, 84108, United States
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
London Sciences Health Center University Hospital
London, Ontario, N6A 5A5, Canada
Parkinson's Disease & Movement Disorders Clinic
Ottawa, Ontario, K1Y 4E9, Canada
Toronto Western Hospital University Health Network
Toronto, Ontario, M5T 2S8, Canada
CHUM-Notre Dame Hospital Unité de Troubles du Mouvement
Montreal, Quebec, H2L 4M1, Canada
McGill University Health Centre - Montreal General Hospital
Montreal, Quebec, H3G 1A4, Canada
Limoges University Hospital
Limoges, 87042, France
Hopital Timone
Marseille, 13385, France
Hôpitaux de Paris
Paris, 75013, France
Humboldt University Charité
Berlin, 13353, Germany
Neurologisch Klinik der Ruhr-Universität im St. Josef-Hospital
Bochum, 44791, Germany
Universitätsklinikum Carl Carus an der Technischen Universität
Dresden, 01307, Germany
Paracelsus-Elena Klinik
Kassel, 34128, Germany
Philipps Universität Marburg
Marburg, 35039, Germany
Klinikum Großhadern
München, 81377, Germany
Universität Rostock Zentrum für Nervenheilkunde und Poliklinik
Rostock, 18147, Germany
Universitäts- und Rehabilitationskliniken Ulm
Ulm, 89081, Germany
Princess Royal Hospital
Haywards Heath, RH16 4EX, United Kingdom
Clinical Ageing Research Unit (CARU) Newcastle University
Newcastle, NE4 5PL, United Kingdom
Greater Manchester Neuroscience Centre
Salford, M6 8HD, United Kingdom
Related Publications (2)
Hoglinger GU, Schope J, Stamelou M, Kassubek J, Del Ser T, Boxer AL, Wagenpfeil S, Huppertz HJ; AL-108-231 Investigators; Tauros MRI Investigators; Movement Disorder Society-Endorsed PSP Study Group. Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. Mov Disord. 2017 Jun;32(6):842-852. doi: 10.1002/mds.26973. Epub 2017 Apr 24.
PMID: 28436538DERIVEDBoxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Hoglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27.
PMID: 24873720DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Adam Boxer, M.D., PhD.
Memory and Aging Center, University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 23, 2010
First Posted
April 27, 2010
Study Start
October 1, 2010
Primary Completion
November 1, 2012
Study Completion
December 1, 2012
Last Updated
January 17, 2013
Record last verified: 2013-01