A Double-blind Study to Investigate Efficacy and Safety of Buntanetap Compared With Placebo in Participants With Early PD

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified January 2025 by Annovis Bio Inc.
Sponsor
Annovis Bio Inc.
Information Provided by (Responsible Party)
Annovis Bio Inc.
Clinicaltrials.gov Identifier
NCT05357989
Other Study ID Numbers:
ANVS-22001
First Submitted
April 18, 2022
First Posted
May 2, 2022
Results First Posted
February 12, 2025
Last Update Posted
March 2, 2025
Last Verified
January 2025

ClinicalTrials.gov processed this data on February 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Parkinson's Disease, Idiopathic
Drug: buntanetap/posiphenDrug: buntanetap/posiphenDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment523 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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 Start DateAugust 2, 2022
Actual Primary Completion DateDecember 3, 2023
Actual Study Completion DateDecember 3, 2023

Groups and Cohorts

Group/CohortIntervention/Treatment
10 mg buntanetap/posiphen
Buntanetap/posiphen 10 mg oral capsule with daily administration for a period of 6 months
Drug: buntanetap/posiphen
HPMC (vegetarian source) capsule shells
20 mg buntanetap/posiphen
Buntanetap/posiphen 20 mg oral capsule with daily administration for a period of 6 months
Drug: buntanetap/posiphen
HPMC (vegetarian source) capsule shells
Placebo
Placebo oral capsule with daily administration for a period of 6 months
Drug: Placebo
HPMC (vegetarian source) capsule shells

Outcome Measures

Primary Outcome Measures
  1. Change From Baseline to Month 6 in MDS-UPDRS Part II (OFF-state)
    Change in the Score from the MDS- Unified Parkinson's Disease Rating Scale (UPDRS) Parts II from Baseline to the End of Trial. MDS-UPDRS Part II (Motor experiences of daily living) has 13 items and the score ranges from 0-52, with higher scores reflecting greater severity.
Secondary Outcome Measures
  1. Change From Baseline to Month 6 in the MDS-UPDRS Part III (OFF-state)
    MDS-UPDRS Part III (motor examination) has 18 items and ranges from 0-132, with higher scores reflecting greater severity.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsAnnovis Bio Inc.
Locations
University of Alabama at Birmingham (UAB)- The Kirklin Clinic | Birmingham Alabama, United States, 35233-2110Banner Sun Health Research Institute - Cleo Roberts Center for Clinical Research | Sun City Arizona, United States, 85351-3020Parkinson's & Movement Disorder Institue (PMDI) - Orange County Office | Fountain Valley California, United States, 92708UCSF Medical Center - Parkinson's Disease and Movement Disorders Clinic | San Francisco California, United States, 94143-2202Rocky Mountain Movement Disorder Center | Englewood Colorado, United States, 80113Ki Health Partners LLC D/B/A New England Institute for Clinical Research | Stamford Connecticut, United States, 06824Visionary Investigators Network | Aventura Florida, United States, 33180Parkinson's Disease and Movement Disorders Center of Boca Raton | Boca Raton Florida, United States, 33486-2359The Neurology Institute - Coral Springs | Coral Springs Florida, United States, 33067-4640Arrow Clinical trial | Daytona Beach Florida, United States, 32114Accel Research Sites - DeLand Clinical Research Unit | DeLand Florida, United States, 32720Coral Clinic Reserach LLC | Homestead Florida, United States, 33032Homestead Associates in Research, Inc | Miami Florida, United States, 33032Visionary Investigators Networks | Miami Florida, United States, 33133Medical Professional Clinical Research Center, INC | Miami Florida, United States, 33165Reliant Medical Research | Miami Florida, United States, 33165Ezy Medical Research Co. | Miami Florida, United States, 33175Visionary Investigators Network | Miami Florida, United States, 33176Renstar Medical Research | Ocala Florida, United States, 34470Visionary Investigators Network | Pembroke Pines Florida, United States, 33026Parkinsons Disease Treatment Center | Port Charlotte Florida, United States, 33952-6705University of South Florida (USF) - University of South Florida College of Medicine- Parkinson's Disease and Movement Disorders Center | Tampa Florida, United States, 33613-4808ClinCloud, LLC | Viera Florida, United States, 32940Conquest Research, LLC | Winter Park Florida, United States, 32789CenExel iResearch, LLC | Decatur Georgia, United States, 30030Hawaii Pacific Neuroscience, LLC | Honolulu Hawaii, United States, 96817Josephson Wallack Munshower Neurology, P.C. | Indianapolis Indiana, United States, 46256University of Kansas Medical Center | Kansas City Kansas, United States, 66160Michigan State University (MSU)- Health Team- Neurology and Ophthalmology Clinic | East Lansing Michigan, United States, 48824-7037Quest Research Institue | Farmington Hills Michigan, United States, 48334Parkinson's Disease and Movement Disorders Center of Long Island | Commack New York, United States, 11725-3400Mount Sinai West (Mount Sinai Roosevelt) | New York New York, United States, 10019-1147Ohio State University Wexner Medical Center (OSUWMC) - CarePoint Gahanna | Columbus Ohio, United States, 43211The Movement Disorder Clinic (MDC) of Oklahoma | Tulsa Oklahoma, United States, 74136-6372Abington Neurology | Abington Pennsylvania, United States, 19001University of Pennsylvania | Philadelphia Pennsylvania, United States, 19107Rhode Island Hospital | Providence Rhode Island, United States, 02903Medical University of South Carolina (MUSC) - The Murray Center for Research on Parkinson's Disease and Related Disorders | Charleston South Carolina, United States, 29401-1189Veracity Neuroscience, LLC | Memphis Tennessee, United States, 38157Central Texas Neurology Consultants | Round Rock Texas, United States, 78681University of Virginia Health System (UVAHS)- Adult Neurology Clinic | Charlottesville Virginia, United States, 22903Inland Northwest Research | Spokane Washington, United States, 99202-1342Medical College of Wisconsin | Milwaukee Wisconsin, United States, 53226Curiositas-ad-sanum GmbH | Haag Bavaria, Germany, 83527Kliniken Beelitz GmbH - Neurologisches Frachkrankenhaus fur Bewegungsstoerungen / Parkinson | Beelitz Brandenburg, Germany, 14547Paracelsus-Kliniken Deutschland GmbH & Co. KGaA - Paracelsus-Elena-Klinik Kassel | Kassel Hesse, Germany, 34128University Hospital Muenster | Münster North Rhine-Westphalia, Germany, 48149Klinik und Poliklinik fur Neurologie - Universitatsklinikum Carl Gustav Carus an der Techischen Universitat | Dresden Saxony, Germany, 01307Neurologie Berlin - Gemeinschaftspraxis Dr. Ehret / Dr. von Pannwitz | Berlin , Germany, 12163Alexianer St. Joseph-Krankenhaus Berlin-Weissensee | Berlin , Germany, 13088Debreceni Egyetem Klinikai Központ Neurológiai Klinika (Kenézy Gyula Campus, Neurológiai Osztály) | Debrecen , Hungary, H-4032PTE AOK Neurologiai Klinika | Pécs , Hungary, H-7623Universita degli Studi di Salerno - Centro per le Malattie Neurodegenerative | Baronissi Campania, Italy, 84081San Raffaele Cassino - Centro di Cura e Prevenzione per il Parkinson | Cassino Lazio, Italy, 3043San Raffaele Pisana - Centro per la Cura e la Diagnosi del Parkinson | Rome Lazio, Italy, 163Pratia MCM Krakow | Krakow Lesser Poland Voivodeship, Poland, 30-727Unicardia Specjalstyczne Centrum Leczenia Chorob Serca I Naczyn&Unimedica Specjalistyczne Centrum Medyczne | Krakow Lesser Poland Voivodeship, Poland, 31-271Krakowska Akademia Neurologil Sp. z o.o. - Centrum Neurologii Klinicznej | Krakow Lesser Poland Voivodeship, Poland, 31-505RCMed Oddzial Sochaczew | Sochaczew Masovian Voivodeship, Poland, 96-500MTZ Clinical Research Powered by Pratia | Warsaw Masovian Voivodeship, Poland, 02-172Specjalistyczna Praktyka Lekarska Dr. Stanislaw Ochudlo | Katowice Silesian Voivodeship, Poland, 40-097NEURO-CARE Sp. z o.o. Sp. Komandytowa | Siemianowice Śląskie Silesian Voivodeship, Poland, 41-100Hospital General Universitario de Elche | Elche Alicante, Spain, 03203Hospital Universitaris General de Catalunya (HGC) | Sant Cugat del Vallès Barcelona, Spain, 8195Policlinica Gipuzkoa - Centro de Invesigacion Parkinson (CIP) | Donostia / San Sebastian Gipuzkoa, Spain, 20014Universidad Complutense de Madrid (UCM) - Hospital Universitario Infanta Sofia | San Sebastián de los Reyes Madrid, Spain, 28701Universidad de Navarra - Clnica Universidad de Navarra (CUN) - Pamplona | Pamplona Navarre, Spain, 31008Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid | Madrid , Spain, 28027Hospital Universitario Virgen del Rocio (URVR - Instituto de Biomedicina de Sevilla (IBIS) | Seville , Spain, 41015
Study Documents (Full Text)
Documents provided by Annovis Bio Inc.: Study Protocol  August 20, 2023Documents provided by Annovis Bio Inc.: Statistical Analysis Plan  January 10, 2024