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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Allon Therapeutics
ClinicalTrials.gov Identifier:
NCT01110720
First received: April 23, 2010
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Progressive Supranuclear Palsy
Drug: Davunetide
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Allon Therapeutics:

Primary Outcome Measures:
  • Efficacy, as measured by change from baseline scores of the Progressive Supranuclear Palsy Rating Scale (PSPRS) at 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Efficacy, as measured by the change from baseline of the Schwab and England Activities of Daily Living Scale (SEADL) at 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Safety, as measured by reported AEs, electrocardiograms (ECG), nasal examinations and clinical laboratory measures [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy, as measured by the Clinical Global Impression of Change (CGI-C) at 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Brain atrophy, as measured by change from baseline of ventricular volumes measured by volumetric brain MRI at 52 weeks. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 313
Study Start Date: October 2010
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Davunetide 30 mg BID Drug: Davunetide
Davunetide Nasal Spray 30 mg BID IN 52 weeks
Placebo Comparator: Placebo Drug: Davunetide
Davunetide Nasal Spray 30 mg BID IN 52 weeks
Drug: Placebo
Placebo Nasal Spray BID IN 52 weeks

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

  Eligibility

Ages Eligible for Study:   41 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110720

  Show 48 Study Locations
Sponsors and Collaborators
Allon Therapeutics
Investigators
Principal Investigator: Adam Boxer, M.D., PhD. Memory and Aging Center, University of California, San Francisco
  More Information

No publications provided by Allon Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Allon Therapeutics
ClinicalTrials.gov Identifier: NCT01110720     History of Changes
Other Study ID Numbers: AL-108-231
Study First Received: April 23, 2010
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Supranuclear Palsy, Progressive
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Neurodegenerative Diseases
Paralysis
Neurologic Manifestations
Eye Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 19, 2014