Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy

NCT ID: NCT01110720

Last Updated: 2013-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

313 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2012-12-31

Brief Summary

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The purpose of the study is to evaluate the safety and efficacy of davunetide for the treatment of Progressive Supranuclear Palsy.

Detailed Description

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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

Conditions

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Progressive Supranuclear Palsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Davunetide 30 mg BID

Group Type EXPERIMENTAL

Davunetide

Intervention Type DRUG

Davunetide Nasal Spray 30 mg BID IN 52 weeks

Placebo

Group Type PLACEBO_COMPARATOR

Davunetide

Intervention Type DRUG

Davunetide Nasal Spray 30 mg BID IN 52 weeks

Placebo

Intervention Type DRUG

Placebo Nasal Spray BID IN 52 weeks

Interventions

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Davunetide

Davunetide Nasal Spray 30 mg BID IN 52 weeks

Intervention Type DRUG

Placebo

Placebo Nasal Spray BID IN 52 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.
* Presence of symptoms for less than 5 years or the presence of symptoms for more than 5 years with a PSPRS baseline score ≥ 40.
* Stable on all other chronic medications for at least 30 days prior to the screening visit (Visit 1).

* 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.
* Clinically significant laboratory abnormalities at screening, including creatinine ≥ 2.5 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of the normal reference range, vitamin B12 below the laboratory normal reference range, or thyroid stimulating hormone TSH above laboratory normal reference range.
* The systolic blood pressure measurement is \> 190 or \< 85 mm Hg. The diastolic blood pressure measurement is \> 105 or \< 50 mm Hg at screening.
* Abnormal ECG tracing at screening and judged to be clinically significant by the site investigator.
* Treatment with any investigational drugs or device within 90 days of screening.
* Known history of serum or plasma progranulin level less than one standard deviation below the normal subject mean for the laboratory performing the assay.
* Known presence of known disease-associated mutation in TDP-43, PGRN, CHMPB2, or VCP genes or any other frontotemporal lobar degeneration (FTLD) causative genes not associated with underlying tau pathology (e.g., Chromosome 9 associated FTD).
* History of deep brain stimulator (DBS) surgery other than sham surgery for DBS clinical trial.
* History of early, prominent rapid eye movement (REM) sleep behavior disorder.
* Women who are pregnant or lactating and women of childbearing potential who are not using at least two different forms of medically recognized and highly effective methods of birth control, resulting in a low failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
* An employee or relative of an employee of the Sponsor, a clinical site, or Contract Research Organization participating in the study.
* Significant anatomical nasal abnormality (e.g., septal deviation obstructing airflow to at least one nostril or septal perforation) or history of nasal turbinate surgery.
* History of a clinically significant medical condition that would interfere with the subject's ability to comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results.
* Contraindication to MRI examination for any reason (e.g., severe claustrophobia, ferromagnetic metal in body).
* Structural abnormality on MRI that precludes diagnosis of PSP, such as cortical infarct in brain region that might account for subject's symptoms.
* In subjects receiving anti-Parkinson's Disease medication at the time of screening, in the opinion of the investigator substantial worsening of motor signs or symptoms compared with normal functioning following overnight withdrawal of the anti-Parkinson medication.
* Known hypersensitivity to davunetide or any ingredient of the formulation.

Exclusion Criteria

* 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:
Minimum Eligible Age

41 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Allon Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adam Boxer, M.D., PhD.

Role: PRINCIPAL_INVESTIGATOR

Memory and Aging Center, University of California, San Francisco

Locations

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University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Muhammed Ali Parkinson Center and Movement Disorders Clinic

Phoenix, Arizona, United States

Site Status

Mayo Clinic, AZ

Scottsdale, Arizona, United States

Site Status

USC Keck School of Medicine

Los Angeles, California, United States

Site Status

David Geffen School of Medicine - UCLA

Los Angeles, California, United States

Site Status

UCSD/VA Neurology Service

San Diego, California, United States

Site Status

UCSF Memory and Aging Center

San Francisco, California, United States

Site Status

Colorado Neurological Institute - Rocky Mountain Movement Disorders Ctr, PC

Englewood, Colorado, United States

Site Status

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Site Status

Mayo Clinic, Florida

Jacksonville, Florida, United States

Site Status

The Frances J. Zesiewicz Foundation for Parkinson's Disease at USF

Tampa, Florida, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center Parkinson Disease & Movement Disorders Center

Kansas City, Kansas, United States

Site Status

University of Louisville Division of Movement Disorders

Louisville, Kentucky, United States

Site Status

John Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Lahey Clinic

Burlington, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Department of Neuology

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic, Rochester, MN

Rochester, Minnesota, United States

Site Status

UMDNJ - Robert Wood Johnson Medical Center

New Brunswick, New Jersey, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Univeristy of North Carolina Department of Neurology

Chapel Hill, North Carolina, United States

Site Status

University Hospitals Case Medical CenterNI Movement Disorders Center

South Euclid, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Utah Center for Alzheimer's Care, Imaging &Research

Salt Lake City, Utah, United States

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

London Sciences Health Center University Hospital

London, Ontario, Canada

Site Status

Parkinson's Disease & Movement Disorders Clinic

Ottawa, Ontario, Canada

Site Status

Toronto Western Hospital University Health Network

Toronto, Ontario, Canada

Site Status

CHUM-Notre Dame Hospital Unité de Troubles du Mouvement

Montreal, Quebec, Canada

Site Status

McGill University Health Centre - Montreal General Hospital

Montreal, Quebec, Canada

Site Status

Limoges University Hospital

Limoges, , France

Site Status

Hopital Timone

Marseille, , France

Site Status

Hôpitaux de Paris

Paris, , France

Site Status

Humboldt University Charité

Berlin, , Germany

Site Status

Neurologisch Klinik der Ruhr-Universität im St. Josef-Hospital

Bochum, , Germany

Site Status

Universitätsklinikum Carl Carus an der Technischen Universität

Dresden, , Germany

Site Status

Paracelsus-Elena Klinik

Kassel, , Germany

Site Status

Philipps Universität Marburg

Marburg, , Germany

Site Status

Klinikum Großhadern

München, , Germany

Site Status

Universität Rostock Zentrum für Nervenheilkunde und Poliklinik

Rostock, , Germany

Site Status

Universitäts- und Rehabilitationskliniken Ulm

Ulm, , Germany

Site Status

Princess Royal Hospital

Haywards Heath, , United Kingdom

Site Status

Clinical Ageing Research Unit (CARU) Newcastle University

Newcastle, , United Kingdom

Site Status

Greater Manchester Neuroscience Centre

Salford, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany United Kingdom

References

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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.

Reference Type DERIVED
PMID: 28436538 (View on PubMed)

Boxer 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.

Reference Type DERIVED
PMID: 24873720 (View on PubMed)

Other Identifiers

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AL-108-231

Identifier Type: -

Identifier Source: org_study_id

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