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

Parkinson's Disease, Idiopathic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05357989
• Other study ID #: ANVS-22001
• Status: Completed
• Phase: Phase 3
• Start date: August 3, 2022
• Est. completion date: December 4, 2023

Study information

• Verified date: February 2024
• Source: Annovis Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 GFAP, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 523
• Est. completion date: December 4, 2023
• Est. primary completion date: December 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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 SSRI or 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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease, Idiopathic

Intervention

Drug:
• buntanetap/posiphen
HPMC (vegetarian source) capsule shells
• Placebo
HPMC (vegetarian source) capsule shells

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Annovis Bio Inc.	TFS Trial Form Support

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 score reflecting greater severity.	Baseline and 6 months visits
Primary	Safety and tolerability	Safety and tolerability assessed by adverse events (AEs), severity of AEs, drug related AEs, AEs leading to study discontinuation, electrocardiogram findings, clinical laboratory test results, vital sign measurements, and physical and neurological examination findings	From consent to end of trial (up to 8 months)
Secondary	Change from Baseline to Month 6 in the sum of MDS-UPDRS Part II+III (OFF-state)	Change in the Sum of the Score from the Activities of Daily Living (ADL) Scale and Motor Examination in the MDS-UPDRS (Parts II+III) 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 score reflecting greater severity MDS-UPDRS Part III (motor examination) has 18 items and ranges from 0-132, with higher scores reflecting greater severity. The sum of Part II+III will be 0-184, with higher scores reflecting greater severity.	Baseline and 6 months visits
Secondary	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	Baseline and 6 months visits
Secondary	Change From Baseline to Month 6 in The Sum of MDS-UPDRS Total Score (OFF-state)	The MDS-Unified Parkinson's Disease Rating Scale (UPDRS) is a 50-item rating scale designed to assess Parkinson's disease-related disability and impairment. The scale comprises four parts: Part I evaluates mentation, behavior, and mood symptoms; Part II evaluates activities of daily living (ADL); Part III evaluates motor function; and Part IV evaluates complications of dopaminergic therapy. The Total score is the sum of the subscale scores for Parts I to III and ranges from 0 to 236, with higher scores reflecting greater severity.	Baseline and 6 months visits
Secondary	Percentage of Responders with "Much Improved" or "Very Much Improved" on Participant Global Impression of Change (PGIC) (ON-state)	The PGIC is the participant-reported outcome. The qualitative assessment of meaningful change will be determined by the participant in response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" Scores are: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. Percentage of responders with much improved and very much improved on PGIC scale will be assessed. PGIC will be taken at home while the subject is during ON-state (with their SOC for Parkinson disease).	1 month, 2 months, 3 months and 6 months visits
Secondary	Change From Baseline to Month 6 on Change on Clinical Global Impression of Severity (CGIS) (OFF-state)	The Clinical Global Impressions Scale on the severity of movement impairment as assessed by the site rater. Site raters will be asked: Considering your total clinical experience with the Parkinson disease population, how ill is the patient at this time? Answers were based on a 7-point scale, with 1=not assessed, 2= very mild, 3= mild, 4= moderate, 5= moderate severe, 6= severe, 7=extremely severe.	Baseline and 6 months visits