Progressive Supranuclear PalsyPhase 1/2NCT04253132
Evaluation of Tolfenamic Acid in Individuals With PSP at 12-Weeks
A Phase 1/2 study testing Tolfenamic Acid in people with Progressive Supranuclear Palsy, run by NeuroTau, Inc. at 1 site in United States.
Trial summary
This is a 12-week study of oral tolfenamic acid vs. placebo in Progressive Supranuclear Palsy (PSP) Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Progressive Supranuclear Palsy
- What is being tested?
- Tolfenamic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2021to 31 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects may be included in the study only if they meet all of the following criteria:
- Probable or possible progressive supranuclear palsy 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 (Visit 1), 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.
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- Aged 41 to 85 years at the time of screening (Visit 1).
- 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. This modified Hachinski will not include the focal neurological signs, symptoms or pseuodobulbar 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 (Visit 1), 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 the 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 (Visit 1).
- 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 other chronic medications for at least 30 days prior to screening.
Who cannot join
- Subjects will be excluded from the study for any of the following reasons:
- Insufficient fluency in local language to complete neuropsychological and functional assessments.
- A diagnosis of Amyotrophic Lateral Sclerosis (ALS) 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,
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- 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 (Visit 1) 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 (Visit 1).
- A history of alcohol or substance abuse within 1 year prior to screening (Visit 1) 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 the one year before the screening visit (Visit 1) 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(Visit 1), 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 the 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 (Visit 1).
- Abnormal ECG tracing at screening (Visit 1) and judged to be clinically significant by the site investigator.
- Treatment with any investigational drugs or device within 90 days of screening (Visit 1).
- 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 surgery other than sham surgery for deep brain stimulation (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 (CRO) 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 the MRI examination for any reason (e.g., severe claustrophobia, ferromagnetic metal in body).
- Structural abnormality on the 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 (Visit 1), 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Lou Ruvo Center for Brain Health - Cleveland Clinic Nevada
Las Vegas, Nevada, 89106
About this study
Official title: A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Tolfenamic Acid for the Treatment of Progressive Supranuclear Palsy
This is a 12-week study of oral tolfenamic acid vs. placebo in Progressive Supranuclear Palsy (PSP)
Read the detailed description
This is a 12-week, Phase 2a randomized, double-blind, placebo-controlled, parallel group study evaluating the safety and efficacy of tolfenamic acid (50 mg, 300 mg, and 600 mg daily) compared with placebo administered to subjects with PSP. The study will include 8 visits and a final telephone contact: screening (Week -6: Visit 1), randomization (7 to 10 days prior to Week 0: visit 2), treatment (Week 0 through Week 12: Visits 2 - 6), end of study Week 12: Visit 7), and telephone contact (Visit 8). Lumbar puncture will be obtained from consenting subjects at screening (Week -6: visit 10 and End of Study (Week 12: Visit 7) to primary exploratory biomarkers.
- Conditions
- Progressive Supranuclear Palsy
- Being tested
- Tolfenamic Acid, Placebos
- Medical subject headings
- Supranuclear Palsy, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolfenamic AcidDrug
Also called NT101
Tolfenamic acid is an NSAID closely resembling mefenamic and flufenamic acid.
PlacebosDrug
Also called placebo
oral placebo
| Study group | Role | What they receive |
|---|---|---|
| 50 mg daily oral dose | Active comparator | 50 mg daily, oral dose of tolfenamic acid Receives: Drug: Tolfenamic Acid |
| 300 mg daily oral dose | Active comparator | 300 mg daily, oral dose of tolfenamic acid Receives: Drug: Tolfenamic Acid |
| 600 mg daily oral dose | Active comparator | 50 mg daily, oral dose of tolfenamic acid Receives: Drug: Tolfenamic Acid |
| Placebo control - 50 mg daily oral dose | Placebo comparator | 50 mg daily oral placebo control Receives: Drug: Placebos |
| Placebo control - 300 mg daily oral dose | Placebo comparator | 300 mg daily oral placebo control Receives: Drug: Placebos |
| Placebo control - 600 mg daily oral dose | Placebo comparator | 600 mg daily oral placebo control Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerance of tolfenamic acid in individuals with PSP
Safety measures include: number of AEs, ECG changes, nasal examination and clinical laboratory tests
Measured: 12-weeks
Secondary outcomes (7)
CSF biomarker change from baseline
total tau, phosphporylated tau, amyloid beta peptide (1-42), NFL, ngrn, pNFH
Measured: 12-weeks
Pharmacodynamic parameter of amyloid beta peptide
To measure treatment effect of tolfenamic acid in amyloid beta peptide concentrations in CSF
Measured: 12-weeks
Pharmacodynamic parameter of total tau
To measure treatment effect of tolfenamic acid in total tau contcentrations in CSF
Measured: 12-weeks
Pharmacodynamic parameter of phosphorylated tau
To measure treatment effect of tolfenamic acid in phosphorylated tau concentrations in CSF
Measured: 12-weeks
Pharmacodynamic parameter of NFL
To measure treatment effect of tolfenamic acid in NFL concentrations in CSF
Measured: 12-weeks
Pharmacodynamic parameter of ngrn
To measure treatment effect of tolfenamic acid in ngrn concentrations in CSF
Measured: 12-weeks
Pharmacodynamic parameter of pNFH
To measure treatment effect of tolfenamic acid in pNFH concentrations in CSF concentrations
Measured: 12-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Jan 2021 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double-blind, placebo-controlled parallel group study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NeuroTau, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- The Cleveland Clinic
- Responsible party
- Principal investigator, Zoltan Mari, MD, The Cleveland Clinic
- Investigators
- Nasser Zawia, PhD, Study director, NeuroTau, Inc.Marwan Sabbagh, MD, Study director, NeuroTau, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04253132
- Sponsor's protocol ID
- NT 101-201
- Status last verified
- Jan 2020
- First submitted
- 17 Dec 2019
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Tolfenamic Acid for the Treatment of Progressive Supranuclear Palsy
- ClinicalTrials.gov ID
- NCT04253132
- Acronym / sponsor ID
- NT 101-201
- Conditions
- Progressive Supranuclear Palsy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- NeuroTau, Inc.University, hospital or other
- Collaborators
- The Cleveland Clinic
- Study start
- 1 Jan 2021 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 12-week study of oral tolfenamic acid vs. placebo in Progressive Supranuclear Palsy (PSP)
Detailed description
This is a 12-week, Phase 2a randomized, double-blind, placebo-controlled, parallel group study evaluating the safety and efficacy of tolfenamic acid (50 mg, 300 mg, and 600 mg daily) compared with placebo administered to subjects with PSP. The study will include 8 visits and a final telephone contact: screening (Week -6: Visit 1), randomization (7 to 10 days prior to Week 0: visit 2), treatment (Week 0 through Week 12: Visits 2 - 6), end of study Week 12: Visit 7), and telephone contact (Visit 8). Lumbar puncture will be obtained from consenting subjects at screening (Week -6: visit 10 and End of Study (Week 12: Visit 7) to primary exploratory biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- This is a randomized, double-blind, placebo-controlled parallel group study.
| Arm | Type | Receives |
|---|---|---|
| 50 mg daily oral dose | Active comparator | Drug: Tolfenamic Acid50 mg daily, oral dose of tolfenamic acid |
| 300 mg daily oral dose | Active comparator | Drug: Tolfenamic Acid300 mg daily, oral dose of tolfenamic acid |
| 600 mg daily oral dose | Active comparator | Drug: Tolfenamic Acid50 mg daily, oral dose of tolfenamic acid |
| Placebo control - 50 mg daily oral dose | Placebo comparator | Drug: Placebos50 mg daily oral placebo control |
| Placebo control - 300 mg daily oral dose | Placebo comparator | Drug: Placebos300 mg daily oral placebo control |
| Placebo control - 600 mg daily oral dose | Placebo comparator | Drug: Placebos600 mg daily oral placebo control |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects may be included in the study only if they meet all of the following criteria:
Key exclusion criteria (34 listed)
- Subjects will be excluded from the study for any of the following reasons:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tolfenamic AcidAlso: NT101Tolfenamic acid is an NSAID closely resembling mefenamic and flufenamic acid. | Drug | 300 mg daily oral dose, 50 mg daily oral dose, 600 mg daily oral dose |
| PlacebosAlso: placebooral placebo | Drug | Placebo control - 300 mg daily oral dose, Placebo control - 50 mg daily oral dose, Placebo control - 600 mg daily oral dose |
Primary outcome
Safety and tolerance of tolfenamic acid in individuals with PSP
Time frame: 12-weeks
Safety measures include: number of AEs, ECG changes, nasal examination and clinical laboratory tests
7 secondary outcomes
CSF biomarker change from baseline
Time frame: 12-weeks
Pharmacodynamic parameter of amyloid beta peptide
Time frame: 12-weeks
Pharmacodynamic parameter of total tau
Time frame: 12-weeks
Pharmacodynamic parameter of phosphorylated tau
Time frame: 12-weeks
Pharmacodynamic parameter of NFL
Time frame: 12-weeks
Pharmacodynamic parameter of ngrn
Time frame: 12-weeks
Pharmacodynamic parameter of pNFH
Time frame: 12-weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nasser Zawia, PhD study director
NeuroTau, Inc.
Marwan Sabbagh, MD study director
NeuroTau, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tolfenamic Acid in people with Progressive Supranuclear Palsy, run by NeuroTau, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zoltan Mari, MD (702 483-6000, mariz@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerance of tolfenamic acid in individuals with PSP (time frame: 12-weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.