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Progressive Supranuclear PalsyPhase 2/3NCT01110720

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

A Phase 2/3 study testing Davunetide in people with Progressive Supranuclear Palsy, run by Allon Therapeutics at 48 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 41 to 85 years
Conditions the study is for
Progressive Supranuclear Palsy
What is being tested?
Davunetide
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
313 participants
Where
48 sitesin 6 countries
Study dates
Oct 2010to Dec 2012
Phase
Phase 2/3
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 41 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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:
  • Abrupt onset of symptoms defined in inclusion criteria 1 associated with ictal events,
  • Head trauma related to onset of symptoms defined in inclusion criteria 1,
  • Severe amnesia within 6 months of the symptoms defined in inclusion criteria 1,
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  • 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.

Trial locations and contacts

48 sites in 6 countries.

48 sites in 6 countries

United States28 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • John Hopkins Hospital

    Baltimore, Maryland, 21287

  • University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Parkinson's Disease and Movement Disorders Center of Boca Raton

    Boca Raton, Florida, 33486

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Univeristy of North Carolina Department of Neurology

    Chapel Hill, North Carolina, 27599

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Colorado Neurological Institute - Rocky Mountain Movement Disorders Ctr, PC

    Englewood, Colorado, 80113

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Mayo Clinic, Florida

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center Parkinson Disease & Movement Disorders Center

    Kansas City, Kansas, 66160

  • USC Keck School of Medicine

    Los Angeles, California, 90033

  • David Geffen School of Medicine - UCLA

    Los Angeles, California, 90095

  • University of Louisville Division of Movement Disorders

    Louisville, Kentucky, 40202

  • University of Minnesota Department of Neuology

    Minneapolis, Minnesota, 55455

  • UMDNJ - Robert Wood Johnson Medical Center

    New Brunswick, New Jersey, 08901

  • Columbia University

    New York, New York, 10032

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Muhammed Ali Parkinson Center and Movement Disorders Clinic

    Phoenix, Arizona, 85013

  • Mayo Clinic, Rochester, MN

    Rochester, Minnesota, 55905

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

    Salt Lake City, Utah, 84108

  • UCSD/VA Neurology Service

    San Diego, California, 92161

  • UCSF Memory and Aging Center

    San Francisco, California, 94143

  • Mayo Clinic, AZ

    Scottsdale, Arizona, 85259

  • University Hospitals Case Medical CenterNI Movement Disorders Center

    South Euclid, Ohio, 44121

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

    Tampa, Florida, 33612

Other trials in United States

Germany8 sites

  • Humboldt University Charité

    Berlin, 13353

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

    Bochum, 44791

  • Universitätsklinikum Carl Carus an der Technischen Universität

    Dresden, 01307

  • Paracelsus-Elena Klinik

    Kassel, 34128

  • Philipps Universität Marburg

    Marburg, 35039

  • Klinikum Großhadern

    München, 81377

  • Universität Rostock Zentrum für Nervenheilkunde und Poliklinik

    Rostock, 18147

  • Universitäts- und Rehabilitationskliniken Ulm

    Ulm, 89081

Other trials in Germany

Canada5 sites

  • London Sciences Health Center University Hospital

    London, Ontario, N6A 5A5

  • CHUM-Notre Dame Hospital Unité de Troubles du Mouvement

    Montreal, Quebec, H2L 4M1

  • McGill University Health Centre - Montreal General Hospital

    Montreal, Quebec, H3G 1A4

  • Parkinson's Disease & Movement Disorders Clinic

    Ottawa, Ontario, K1Y 4E9

  • Toronto Western Hospital University Health Network

    Toronto, Ontario, M5T 2S8

Other trials in Canada

France3 sites

  • Limoges University Hospital

    Limoges, 87042

  • Hopital Timone

    Marseille, 13385

  • Hôpitaux de Paris

    Paris, 75013

Other trials in France

United Kingdom3 sites

  • Princess Royal Hospital

    Haywards Heath, RH16 4EX

  • Clinical Ageing Research Unit (CARU) Newcastle University

    Newcastle, NE4 5PL

  • Greater Manchester Neuroscience Centre

    Salford, M6 8HD

Other trials in United Kingdom

Australia1 site

  • The Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: 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

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

Read the detailed description

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

Being tested
Davunetide, Placebo
Medical subject headings
Supranuclear Palsy, Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DavunetideDrug

    Davunetide Nasal Spray 30 mg BID IN 52 weeks

  • PlaceboDrug

    Placebo Nasal Spray BID IN 52 weeks

Study groups in NCT01110720
Study groupRoleWhat they receive
Davunetide 30 mg BIDExperimentalNot described
Receives: Drug: Davunetide
PlaceboPlacebo comparatorNot described
Receives: Drug: Davunetide; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy, as measured by change from baseline scores of the Progressive Supranuclear Palsy Rating Scale (PSPRS) at 52 weeks

    Measured: 52 weeks

  2. Efficacy, as measured by the change from baseline of the Schwab and England Activities of Daily Living Scale (SEADL) at 52 weeks

    Measured: 52 weeks

  3. Safety, as measured by reported AEs, electrocardiograms (ECG), nasal examinations and clinical laboratory measures

    Measured: 52 weeks

Secondary outcomes (2)

  1. Efficacy, as measured by the Clinical Global Impression of Change (CGI-C) at 52 weeks

    Measured: 52 weeks

  2. Brain atrophy, as measured by change from baseline of ventricular volumes measured by volumetric brain MRI at 52 weeks.

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionNov 2012
  4. Study completionDec 2012

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
313 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01110720
Sponsor's protocol ID
AL-108-231
Status last verified
Jan 2013
First submitted
23 Apr 2010
Last updated
17 Jan 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Quattrone A, Franzmeier N, Huppertz HJ, Klietz M, Roemer SN, Boxer AL, Levin J, Hoglinger GU; AL-108-231 Investigators, the Tauros MRI Investigators, the PASSPORT Study Group, the DESCRIBE-PSP Group. Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials. Mov Disord. 2024 Aug;39(8):1329-1342. doi: 10.1002/mds.29866. Epub 2024 Jun 2.

    PubMed 38825840

  • 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.

    PubMed 28436538

  • 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.

    PubMed 24873720

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Davunetide in people with Progressive Supranuclear Palsy, run by Allon Therapeutics at 48 sites in 6 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 17 inclusion and 34 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 17 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Germany, Canada, France, United Kingdom and 1 more country. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Efficacy, as measured by change from baseline scores of the Progressive Supranuclear Palsy Rating Scale (PSPRS) at 52 weeks (time frame: 52 weeks). The study lists 3 primary outcomes in all. 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 NCT01110720, which also lists 3 linked publications.

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 17 Jan 2013.

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