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