Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy
This study has been completed.
Information provided by (Responsible Party):
First received: April 23, 2010
Last updated: January 15, 2013
Last verified: January 2013
The purpose of the study is to evaluate the safety and efficacy of davunetide for the treatment of Progressive Supranuclear Palsy.
Progressive Supranuclear Palsy
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||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
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 ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||November 2012 (Final data collection date for primary outcome measure)
Experimental: Davunetide 30 mg BID
Davunetide Nasal Spray 30 mg BID IN 52 weeks
Placebo Comparator: Placebo
Davunetide Nasal Spray 30 mg BID IN 52 weeks
Placebo Nasal Spray BID IN 52 weeks
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
|Ages Eligible for Study:
||41 Years to 85 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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,
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01110720
||Adam Boxer, M.D., PhD.
||Memory and Aging Center, University of California, San Francisco
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 23, 2010
||January 15, 2013
||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:
ClinicalTrials.gov processed this record on March 05, 2014
Supranuclear Palsy, Progressive
Basal Ganglia Diseases
Central Nervous System Diseases
Nervous System Diseases
Ocular Motility Disorders
Cranial Nerve Diseases
Signs and Symptoms