Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01110720




Registration number
NCT01110720
Ethics application status
Date submitted
23/04/2010
Date registered
27/04/2010
Date last updated
17/01/2013

Titles & IDs
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
Secondary ID [1] 0 0
AL-108-231
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressive Supranuclear Palsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Davunetide
Treatment: Drugs - Placebo

Experimental: Davunetide 30 mg BID -

Placebo Comparator: Placebo -


Treatment: Drugs: Davunetide
Davunetide Nasal Spray 30 mg BID IN 52 weeks

Treatment: Drugs: Placebo
Placebo Nasal Spray BID IN 52 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Efficacy, as measured by change from baseline scores of the Progressive Supranuclear Palsy Rating Scale (PSPRS) at 52 weeks
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
Efficacy, as measured by the change from baseline of the Schwab and England Activities of Daily Living Scale (SEADL) at 52 weeks
Timepoint [2] 0 0
52 weeks
Primary outcome [3] 0 0
Safety, as measured by reported AEs, electrocardiograms (ECG), nasal examinations and clinical laboratory measures
Timepoint [3] 0 0
52 weeks
Secondary outcome [1] 0 0
Efficacy, as measured by the Clinical Global Impression of Change (CGI-C) at 52 weeks
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Brain atrophy, as measured by change from baseline of ventricular volumes measured by volumetric brain MRI at 52 weeks.
Timepoint [2] 0 0
52 weeks

Eligibility
Key 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).
Minimum age
41 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2012
Sample size
Target
Accrual to date
Final
313
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
France
State/province [22] 0 0
Limoges
Country [23] 0 0
France
State/province [23] 0 0
Marseille
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Germany
State/province [26] 0 0
Bochum
Country [27] 0 0
Germany
State/province [27] 0 0
Dresden
Country [28] 0 0
Germany
State/province [28] 0 0
Kassel
Country [29] 0 0
Germany
State/province [29] 0 0
Marburg
Country [30] 0 0
Germany
State/province [30] 0 0
München
Country [31] 0 0
Germany
State/province [31] 0 0
Rostock
Country [32] 0 0
Germany
State/province [32] 0 0
Ulm
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Haywards Heath
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Newcastle
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Allon Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to evaluate the safety and efficacy of davunetide for the
treatment of Progressive Supranuclear Palsy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01110720
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Adam Boxer, M.D., PhD.
Address 0 0
Memory and Aging Center, University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01110720