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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01110720
• Date of registration: 23/04/2010
• Prospective Registration: Yes
• Primary sponsor: Allon Therapeutics
• Public title: Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy
• Scientific 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
• Date of first enrolment: October 2010
• Target sample size: 313
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01110720
• 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
• Phase: Phase 2/Phase 3

Countries of recruitment

Australia, Canada, France, Germany, United Kingdom, United States

Contacts

• Name: Adam Boxer, M.D., PhD.
• Affiliation: Memory and Aging Center, University of California, San Francisco

Key inclusion & exclusion 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.




Age minimum: 41 Years
Age maximum: 85 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Progressive Supranuclear Palsy

Intervention(s)

Drug: Davunetide

Drug: Placebo

Primary Outcome(s)

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

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]

Safety, as measured by reported AEs, electrocardiograms (ECG), nasal examinations and clinical laboratory measures [Time Frame: 52 weeks]

Secondary Outcome(s)

Brain atrophy, as measured by change from baseline of ventricular volumes measured by volumetric brain MRI at 52 weeks. [Time Frame: 52 weeks]

Efficacy, as measured by the Clinical Global Impression of Change (CGI-C) at 52 weeks [Time Frame: 52 weeks]

Secondary ID(s)

AL-108-231

Source(s) of Monetary Support

Please refer to primary and secondary sponsors