Clinical trial NCT05357989: A Double-blind Study to Investigate Efficacy and Safety of Buntanetap Compared With Placebo in Participants With Early PD
Official title: A 6-month Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial Investigating the Efficacy, Safety, and Tolerability of Two Different Doses of Buntanetap or Placebo in Patients With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease, Idiopathic
Keywords: Parkinson's
Lead sponsor: Annovis Bio Inc.
Sponsor class: INDUSTRY
Collaborators: name: TFS Trial Form Support
First posted: 2022-05-03
Enrollment: 523
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure safety and efficacy of buntanetap/posiphen capsules compared with placebo capsules in participants with early PD.

Study details include:

* The study duration will be up to 7-8 months.
* The double-blind treatment duration will be up to 6 months.
* There will be 5 in-clinic visits and 7 phone calls

Detailed description: 450 early Parkinson's Disease (PD) patients will be randomized to 10mg, 20 mg of buntanetap/posiphen or placebo. They will undergo a Screening Visit, and if they provide informed consent and are considered eligible per the inclusion and exclusion criteria, will proceed to participate in the treatment period. Randomized participants will visit the clinic for the first-time dosing in clinic with administration of 10 mg or 20mg of buntanetap/posiphen or placebo, followed by an at home dosing period of 6 months, with daily administration of 10 mg or 20mg of buntanetap/posiphen or Placebo. Participants will be required to visit clinics 1 month, 2 months, 3 months, and 6 months (end-of-trial), where they will undergo study procedures that include safety assessments (AE and concomitant medication monitoring, 12-lead ECGs, clinical laboratory testing, vital signs assessments, and physical examinations) and psychometric tests (MDS-United Parkinson's Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Severity (CGIS), Wechsler Adult Intelligence Scales (WAIS), Mini-Mental State Examination (MMSE)) and Participant Global Impression of Change (PGIC). At the end of blood sampling, the subjects will need to stay for a minimum of 1 hour of observation. After all end-of-study procedures are complete, the subject will be discharged to home. A 24-hour follow-up call will occur after all clinical visits to assess the participants current condition and if there are any additional adverse events to report.

Buntanetap/posiphen has shown to improve PD subjects' mobility. MDS-UPDRS sum of score of Part II + Part III and Total score of all four parts will be measured to assess its improvement on PD subjects daily living, mobility and complications. PGIC will also be measured to assess its effect.

Buntanetap/posiphen has shown to reduce inflammation and preserve axonal integrity and synaptic functions as well as neurotoxic proteins in previous Phase 2a studies. In this study we plan to measure plasma glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and potentially TDP43.

Reports of adverse events (AEs) and serious adverse events (SAEs) during exposure to buntanetap/posiphen will be collected to evaluate if there are any significant clinical safety issues for the study population. Extensive clinical and laboratory safety data already exist for buntanetap/posiphen; therefore, these safety measures will be sufficient in the proposed study.

For clinical, functional, and cognitive assessment measures, The subjects will be administered the Hoehn \& Yahr and the MMSE for determination of inclusion into the study. The MDS-UPDRS and PGIC will be administered for subjects' movement and daily function. The Coding subtest from the WAIS 4th edition will serve as a sensitive measure of Central Nervous System (CNS) dysfunction. MMSE will also be measured to assess subjects' cognitive change.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of idiopathic Parkinson Disease according to MDS Clinical Diagnostic Criteria for Parkinson's Disease.
2. H\&Y score =1, 2 or 3 during ON-state \& OFF-state \<2hrs per day.
3. Male or female aged 40 - 85 years.
4. MMSE score between the range of 22-30 during screening visit (ON-state) and subjects can live independently without a caregiver.
5. Female subjects of childbearing potential\* must have a negative serum or urine pregnancy test at Screening, must be non-lactating and must agree to use a highly effective method of contraception (i.e., a method resulting in a failure rate of less than 1% per year when used consistently and correctly) during the trial and for 4 weeks after the last dose of trial treatment, such as:

   * Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation
   * Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
   * Intrauterine device (IUD)
   * Intrauterine hormone-releasing system (IUS)
   * Bilateral tubal occlusion
   * Vasectomized partner (a vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the participant, and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used)
   * Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant) \*Non-childbearing potential includes surgically sterilized or postmenopausal with no menstrual bleeding for at least one year prior to study start.
6. Male subjects must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subject must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:

   * Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation
   * Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
   * Intrauterine device (IUD)
   * Intrauterine hormone-releasing system (IUS)
   * Bilateral tubal occlusion 6. Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
7. General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.
8. No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
9. Stability of permitted medications prior to screening for at least 4 weeks.
10. At screening subjects do not need to but may be on the following medication:

    * Standard of Care anti-parkinsonian medication
    * Anticonvulsant medications used for epilepsy or mood stabilization, neuropathic pain indications
    * Mood-stabilizing psychotropic agents, including, but not limited to, lithium.
11. Adequate visual and hearing ability (physical ability to perform all the study assessments).
12. Good general health with no disease expected to interfere with the study.
13. Subjects previously exposed to buntanetap can still be included in the study after a 28- day wash out period.

Exclusion Criteria:

1. Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or history of depression that is stable on treatment with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) medication at a stable dose is acceptable.
2. History of a seizure disorder, if stable on medication is acceptable.
3. Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 475ms, or torsades de pointes.
4. Has bradycardia (\<50 bpm) or tachycardia (\>100 bpm) on the ECG at screening.
5. Has uncontrolled Type-1 or Type-2 diabetes. A subject with HbA1c levels up to 7.5% can be enrolled if the investigator believes the subject's diabetes is under control.
6. Has clinically significant renal or hepatic impairment.
7. Has any clinically significant abnormal laboratory values. Subjects with liver function tests (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) greater than twice the upper limit of normal will be excluded.
8. Is at imminent risk of self-harm, based on clinical interview and responses on the C SSRS, or of harm to others in the opinion of the Investigators. Subjects must be excluded if they report suicidal ideation with intent, with or without a plan or method (e. g. positive response to Items 4 or 5 in assessment of suicidal ideation on the C SSRS) in the past 2 months, or suicidal behavior in the past 6 months.
9. Has cancer or has had a malignant tumor within the past year, except subjects who underwent potentially curative therapy with no evidence of recurrence. (Subjects with stable untreated prostate cancer or skin cancers are not excluded).
10. Alcohol / Substance use disorder, moderate to severe, in the last 5 years according to the most current version DSM.
11. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 60 days prior to the start of screening. The end of a previous investigational trial is the date the last dose of an investigational agent was taken, or five half-lives of the investigational drug, whichever is greater.
12. Subjects with learning disability or developmental delay.
13. Subjects whom the site PI deems to be otherwise ineligible.
14. Subjects with a known allergy to the investigational drug or any of its components.
15. Subject is currently pregnant, breast-feeding and/or lactating.
16. Subject is currently taking CYP3A4 inhibitors and/or inducers.

Primary outcomes:
measure: Change From Baseline to Month 6 in MDS-UPDRS Part II (OFF-state)
timeFrame: Baseline and 6 months visits
Secondary outcomes:
measure: Change From Baseline to Month 6 in the MDS-UPDRS Part III (OFF-state)
timeFrame: Baseline and 6 months visits
Other outcomes:
measure: Change From Baseline to Month 6 in MMSE (OFF-state)
timeFrame: Baseline and 6 months visits
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB)- The Kirklin Clinic
state: Alabama
city: Sun City
country: United States
facility: Banner Sun Health Research Institute - Cleo Roberts Center for Clinical Research
state: Arizona
city: Fountain Valley
country: United States
facility: Parkinson's & Movement Disorder Institue (PMDI) - Orange County Office
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center - Parkinson's Disease and Movement Disorders Clinic
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorder Center
state: Colorado
city: Stamford
country: United States
facility: Ki Health Partners LLC D/B/A New England Institute for Clinical Research
state: Connecticut
city: Aventura
country: United States
facility: Visionary Investigators Network
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Coral Springs
country: United States
facility: The Neurology Institute - Coral Springs
state: Florida
city: Daytona Beach
country: United States
facility: Arrow Clinical trial
state: Florida
city: DeLand
country: United States
facility: Accel Research Sites - DeLand Clinical Research Unit
state: Florida
city: Homestead
country: United States
facility: Coral Clinic Reserach LLC
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research, Inc
state: Florida
city: Miami
country: United States
facility: Visionary Investigators Networks
state: Florida
city: Miami
country: United States
facility: Medical Professional Clinical Research Center, INC
state: Florida
city: Miami
country: United States
facility: Reliant Medical Research
state: Florida
city: Miami
country: United States
facility: Ezy Medical Research Co.
state: Florida
city: Miami
country: United States
facility: Visionary Investigators Network
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Pembroke Pines
country: United States
facility: Visionary Investigators Network
state: Florida
city: Port Charlotte
country: United States
facility: Parkinsons Disease Treatment Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida (USF) - University of South Florida College of Medicine- Parkinson's Disease and Movement Disorders Center
state: Florida
city: Viera
country: United States
facility: ClinCloud, LLC
state: Florida
city: Winter Park
country: United States
facility: Conquest Research, LLC
state: Florida
city: Decatur
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience, LLC
state: Hawaii
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, P.C.
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: East Lansing
country: United States
facility: Michigan State University (MSU)- Health Team- Neurology and Ophthalmology Clinic
state: Michigan
city: Farmington Hills
country: United States
facility: Quest Research Institue
state: Michigan
city: Commack
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Long Island
state: New York
city: New York
country: United States
facility: Mount Sinai West (Mount Sinai Roosevelt)
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center (OSUWMC) - CarePoint Gahanna
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic (MDC) of Oklahoma
state: Oklahoma
city: Abington
country: United States
facility: Abington Neurology
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - The Murray Center for Research on Parkinson's Disease and Related Disorders
state: South Carolina
city: Memphis
country: United States
facility: Veracity Neuroscience, LLC
state: Tennessee
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System (UVAHS)- Adult Neurology Clinic
state: Virginia
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Haag
country: Germany
facility: Curiositas-ad-sanum GmbH
state: Bavaria
city: Beelitz
country: Germany
facility: Kliniken Beelitz GmbH - Neurologisches Frachkrankenhaus fur Bewegungsstoerungen / Parkinson
state: Brandenburg
city: Kassel
country: Germany
facility: Paracelsus-Kliniken Deutschland GmbH & Co. KGaA - Paracelsus-Elena-Klinik Kassel
state: Hesse
city: Muenster
country: Germany
facility: University Hospital Muenster
state: North Rhine-Westphalia
city: Dresden
country: Germany
facility: Klinik und Poliklinik fur Neurologie - Universitatsklinikum Carl Gustav Carus an der Techischen Universitat
state: Saxony
city: Berlin
country: Germany
facility: Neurologie Berlin - Gemeinschaftspraxis Dr. Ehret / Dr. von Pannwitz
city: Berlin
country: Germany
facility: Alexianer St. Joseph-Krankenhaus Berlin-Weissensee
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Neurológiai Klinika (Kenézy Gyula Campus, Neurológiai Osztály)
city: Pecs
country: Hungary
facility: PTE AOK Neurologiai Klinika
city: Baronissi
country: Italy
facility: Universita degli Studi di Salerno - Centro per le Malattie Neurodegenerative
state: Campania
city: Cassino
country: Italy
facility: San Raffaele Cassino - Centro di Cura e Prevenzione per il Parkinson
state: Lazio
city: Rome
country: Italy
facility: San Raffaele Pisana - Centro per la Cura e la Diagnosi del Parkinson
state: Lazio
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologil Sp. z o.o. - Centrum Neurologii Klinicznej
state: Malopolskie
city: Kraków
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Kraków
country: Poland
facility: Unicardia Specjalstyczne Centrum Leczenia Chorob Serca I Naczyn&Unimedica Specjalistyczne Centrum Medyczne
state: Malopolskie
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
state: Mazowieckie
city: Warsaw
country: Poland
facility: MTZ Clinical Research Powered by Pratia
state: Mazowieckie
city: Katowice
country: Poland
facility: Specjalistyczna Praktyka Lekarska Dr. Stanislaw Ochudlo
state: Silesia
city: Siemianowice Śląskie
country: Poland
facility: NEURO-CARE Sp. z o.o. Sp. Komandytowa
state: Silesia
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitaris General de Catalunya (HGC)
state: Barcelona
city: Donostia-San Sebastian
country: Spain
facility: Policlinica Gipuzkoa - Centro de Invesigacion Parkinson (CIP)
state: Gipuzkoa
city: San Sebastián De Los Reyes
country: Spain
facility: Universidad Complutense de Madrid (UCM) - Hospital Universitario Infanta Sofia
state: Madrid
city: Pamplona
country: Spain
facility: Universidad de Navarra - Clnica Universidad de Navarra (CUN) - Pamplona
state: Navarra
city: Madrid
country: Spain
facility: Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio (URVR - Instituto de Biomedicina de Sevilla (IBIS)
Study officials:
References: