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

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Brief Title

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

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

Brief Summary

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

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
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

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

Condition

Progressive Supranuclear Palsy

Intervention

Davunetide

Study Arms / Comparison Groups

 Davunetide 30 mg BID
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

313

Start Date

October 2010

Completion Date

December 2012

Primary Completion Date

November 2012

Eligibility Criteria

        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).

        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:

               -  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,

               -  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.
      

Gender

All

Ages

41 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

Adam Boxer, M.D., PhD., , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT01110720

Organization ID

AL-108-231


Responsible Party

Sponsor

Study Sponsor

Allon Therapeutics


Study Sponsor

Adam Boxer, M.D., PhD., Principal Investigator, Memory and Aging Center, University of California, San Francisco


Verification Date

January 2013