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Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of TB006 in Participants With Alzheimer's Disease

Sponsor
TrueBinding, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT05074498
Collaborator
(none)
140
Enrollment
18
Locations
4
Arms
12.2
Anticipated Duration (Months)
7.8
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Part 1 of this study will be conducted to determine the safety, tolerability, and pharmacokinetic (PK) profile of multiple doses of TB006, as well as the maximum tolerated dose of TB006, and to assess the immunogenicity of TB006 (production of anti-TB006 antibody). Part 2 of this study will be conducted to determine the clinical efficacy of TB006 in participants with mild to severe Alzheimer's Disease.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Seamless Phase 1b/2a Double-blind, Randomized, Multiple Dose, Multi-center, Sequential Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of TB006 in Patients With Mild to Severe Alzheimer's Disease
Actual Study Start Date :
Oct 8, 2021
Anticipated Primary Completion Date :
Oct 15, 2022
Anticipated Study Completion Date :
Oct 15, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: TB006

Participants will be randomized to 1 of 3 ascending dose groups to receive a total of 5 once-weekly doses of TB006, infused over 1 hour.

Drug: TB006
intravenous infusion
Placebo Comparator: Part 1: Placebo

Participants will be randomized to receive 5 once-weekly doses of matching placebo.

Drug: Placebo
intravenous infusion
Experimental: Part 2: TB006

Participants will receive the highest safe and well-tolerated dose identified in Part 1, infused over 1 hour. Randomization will be stratified according to severity at Baseline (mild versus moderate Alzheimer's Disease).

Drug: TB006
intravenous infusion
Placebo Comparator: Part 2: Placebo

Participants will be randomized to receive matching placebo. Randomization will be stratified according to severity at Baseline (mild versus moderate Alzheimer's Disease).

Drug: Placebo
intravenous infusion

Outcome Measures

Primary Outcome Measures

  1. Part 1: Number of Participants with Treatment-emergent Adverse Events [up to Day 104 after first TB006 dosing]

  2. Part 1: Number of Participants with Clinically Significant Clinical Laboratory Parameter Values [up to Day 104 after first TB006 dosing]

  3. Part 1: Number of Participants with Clinically Significant Vital Sign Values [up to Day 104 after first TB006 dosing]

  4. Part 1: Number of Participants with Clinically Significant 12-Lead Electrocardiogram Findings [up to Day 104 after first TB006 dosing]

  5. Part 1: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Scores [up to Day 104 after first TB006 dosing]

  6. Part 1: Number of Participants with Clinically Significant Physical Examination Findings [up to Day 104 after first TB006 dosing]

  7. Part 1: Number of Participants with Clinically Significant Neurological Examination Findings [up to Day 104 after first TB006 dosing]

  8. Part 1: Area under the Concentration Time Curve over a Dosing Interval (AUCtau) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  9. Part 1: Maximum Observed Plasma Concentration (Cmax) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  10. Part 1: Time at which Maximum Plasma Concentration Occurs (tmax) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  11. Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  12. Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  13. Part 1: Total Clearance (CL) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  14. Part 1: Volume of Distribution (Vd) of TB006 [Pre-dose, end of infusion, then 1, 2, 4, and 6 hours after the end of infusion on Days 1, 8, and 29; single time point on Days 36, 64, and 104]

  15. Part 1: Concentrations of TB006 in Cerebrospinal Fluid (CSF), as a Measure of the Extent of CSF Distribution [Day -1 and Day 36]

  16. Part 1: Number of Participants with Anti-TB006 Antibodies [Day 1 (pre-dose)]

  17. Part 1: Number of Participants with Anti-TB006 Antibodies [Day 8 (pre-dose)]

  18. Part 1: Number of Participants with Anti-TB006 Antibodies [Day 36]

  19. Part 1: Number of Participants with Anti-TB006 Antibodies [Day 104]

  20. Part 2: Change from Baseline through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score [Baseline; Day 104]

Secondary Outcome Measures

  1. Part 2: Change from Baseline through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score [Baseline; Day 36]

  2. Part 2: Number of Responders on the Clinical Dementia Rating Scale - Sum of Boxes at Days 36 and 104 [Baseline; Days 36 and 104]

  3. Part 2: Change from Baseline to Days 36 and 104 on the Cognitive Drug Research System Battery, Composite Scores and Individual Task Measures [Baseline; Days 36 and 104]

  4. Part 2: Change from Baseline to Days 36 and 104 on the Mini-Mental State Examination (MMSE) Score [Baseline; Days 36 and 104]

  5. Part 2: Change from Baseline to Days 36 and 104 on the Neuropsychiatric Inventory (NPI) Score [Baseline; Days 36 and 104]

  6. Part 2: Number of Participants with Treatment-emergent Adverse Events [up to Day 104 after first TB006 dosing]

  7. Part 2: Number of participants with Clinically Significant Clinical Laboratory Parameter Values [up to Day 104 after first TB006 dosing]

  8. Part 2: Number of Participants with Clinically Significant Vital Sign Values [up to Day 104 after first TB006 dosing]

  9. Part 2: Number of Participants with Clinically Significant 12-Lead Electrocardiogram Findings [up to Day 104 after first TB006 dosing]

  10. Part 2: Change from Baseline in C-SSRS Scores [up to Day 104 after first TB006 dosing]

  11. Part 2: Number of Participants with Clinically Significant Physical Examination Findings [up to Day 104 after first TB006 dosing]

  12. Part 2: Number of Participants with Clinically Significant Neurological Examination Findings [up to Day 104 after first TB006 dosing]

  13. Part 2: Ctrough of TB006 [Pre-dose and the end of infusion on Day 1 and Day 29; single time point on Days 36, 64, and 104]

  14. Part 2: Cmax of TB006 [Pre-dose and the end of infusion on Day 1 and Day 29; single time point on Days 36, 64, and 104]

  15. Part 2: t1/2 of TB006 [Pre-dose and the end of infusion on Day 1 and Day 29; single time point on Days 36, 64, and 104]

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Body weight of ≥ 50 kilograms (kg) and body mass index (BMI) between 18 and 35 kg/meters squared (m^2), inclusive

  • Mini-Mental State Examination (MMSE) score of 24 or less

  • Must be ambulatory

  • Clinical diagnosis of Alzheimer's Disease (AD) consistent with the following:

  1. Probable AD, according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)

  2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) - Criteria for Major Neurocognitive Disorder (previously dementia)

Exclusion Criteria:

  • Any medical or neurological condition other than AD that in the opinion of the investigator could be a contributing cause of the participant's dementia (e.g., medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, diffuse Lewy body disease, head trauma)

  • History within the past 6 months or evidence of clinically significant psychiatric illness (e.g., major depression, schizophrenia, or bipolar affective disorder)

  • Diagnosis of a dementia-related central nervous system (CNS) disease other than AD (e.g., Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus)

  • Identification of other known cause of dementia or any other clinically significant contributing co-morbid pathologies at screening magnetic resonance imaging (MRI), in the opinion of the investigator

  • Participation in any other drug, biologic, device, or clinical study or treatment with any investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to screening, and/or participation in any other clinical study involving experimental medications for AD within the 60 days (or 5 half lives, whichever is longer) prior to screening

Contacts and Locations

Locations

Site City State Country Postal Code
1 Clinical Trial Site Garden Grove California United States 92845
2 Clinical Trial Site San Diego California United States 92103
3 Clinical Trial Site Delray Beach Florida United States 33445
4 Clinical Trial Site Lady Lake Florida United States 32159
5 Clinical Trial Site #1 Maitland Florida United States 32751
6 Clinical Trial Site Maitland Florida United States 32751
7 Clinical Trial Site Miami Florida United States 33126
8 Clinical Trial Site Miami Florida United States 33135
9 Clinical Trial Site Miami Florida United States 33137
10 Clinical Trial Site Miami Florida United States 33165
11 Clinical Trial Site Stuart Florida United States 34997
12 Clinical Trial Site West Palm Beach Florida United States 33407
13 Clinical Trial Site Winter Park Florida United States 32789
14 Clinical Trial Site Winter Park Florida United States 32792
15 Clinical Trial Site Decatur Georgia United States 30033
16 Clinical Trial Site Matthews North Carolina United States 28105
17 Clinical Trial Site DeSoto Texas United States 75115
18 Clinical Trial Site Fairfax Virginia United States 22031

Sponsors and Collaborators

  • TrueBinding, Inc.

Investigators

  • Study Director: TrueBinding, Inc., TrueBinding, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
TrueBinding, Inc.
ClinicalTrials.gov Identifier:
NCT05074498
Other Study ID Numbers:
  • TB006AD2102
First Posted:
Oct 12, 2021
Last Update Posted:
Jun 1, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by TrueBinding, Inc.
TB006
pharmacokinetics
pharmacodynamics
immunogenicity
mild to severe Alzheimer's Disease
Additional relevant MeSH terms:
Alzheimer Disease

Study Results

No Results Posted as of Jun 1, 2022