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

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT05074498

Acronym / sponsor ID

TB006AD2102

Conditions

Alzheimer's Disease

Keywords

TB006, pharmacokinetics, pharmacodynamics, immunogenicity, mild to severe Alzheimer's Disease

Phase

Phase 1/2

Study type

Interventional

Recruitment status

Completed

Enrolment

154 participants (actual)

Lead sponsor

TrueBinding, Inc.Industry (pharma, biotech, devices)

Study start

8 Oct 2021 (actual)

Primary completion

13 Oct 2022 (actual)

Study completion

13 Oct 2022 (actual)

First posted

12 Oct 2021 (actual)

Results

Posted 18 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Sequential

Masking

Triple blind (participant, investigator, outcomes assessor)

Number of arms

4

Who may qualify

Ages

50 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

   Time frame: Up to Day 104

   An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.

2. Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

3. Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

4. Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

5. Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

6. Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

7. Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following clinical chemistry parameters including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

8. Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

9. Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)

   Time frame: Baseline and up to Day 104

   Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

10. Part 1: Change From Baseline in Hematology Parameter: Hematocrit

    Time frame: Baseline and up to Day 104

    Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

11. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes

    Time frame: Baseline and up to Day 104

    Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

12. Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)

    Time frame: Baseline and up to Day 104

    Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

13. Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

    Time frame: Baseline and up to Day 104

    Blood samples were collected for analysis of following hematology parameter: Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

14. Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)

    Time frame: Baseline and up to Day 104

    Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

15. Part 1: Change From Baseline in Urine Specific Gravity

    Time frame: Baseline and up to Day 104

    Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

16. Part 1: Change From Baseline in Urobilinogen

    Time frame: Baseline and up to Day 104

    Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.

17. Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

    Time frame: Baseline and Up to Day 104

    Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.

18. Part 1: Change From Baseline in Respiratory Rate

    Time frame: Baseline and Up to Day 104

    Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.

19. Part 1: Change From Baseline in Temperature

    Time frame: Baseline and Up to Day 104

    Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.

20. Part 1: Change From Baseline in Heart Rate

    Time frame: Baseline and Up to Day 104

    Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.

21. Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate

    Time frame: Baseline and Up to Day 104

    12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value value.

22. Part 1: Change From Baseline in ECG Parameters

    Time frame: Baseline and Up to Day 104

    12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QT Corrected using Bazett's formula (QTcB). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.

23. Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)

    Time frame: Up to Day 104

    The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms.

24. Part 1: Number of Participants With Clinically Significant Physical Examination Findings

    Time frame: Up to Day 104

    A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

25. Part 1: Number of Participants With Clinically Significant Neurological Examination Findings

    Time frame: Up to Day 104

    The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

26. Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006

    Time frame: Day 1 and Day 29

    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. AUCtau normalized to the actual administered dose is presented. The AUCtau was divided by the actual dose strength to get the normalized area under the concentration-time curve.

27. Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006

    Time frame: At Days 1, 8 and 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

28. Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006

    Time frame: At Days 1, 8 and 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. Cmax normalized to the actual administered dose is presented. The Cmax was divided by the actual dose strength to get the normalized maximum observed plasma concentration.

29. Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006

    Time frame: Day 8 and Day 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

30. Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006

    Time frame: At Day 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

31. Part 1: Total Clearance (CL) of TB006

    Time frame: At Day 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

32. Part 1: Volume of Distribution (Vd) of TB006

    Time frame: At Day 29

    Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

33. Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)

    Time frame: Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104

    Plasma samples were collected at indicated time points for the determination of anti-TB006 antibodies. Plasma samples were screened for antibodies binding to TB006 and the titer of confirmed positive samples has been reported.

34. Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score

    Time frame: Baseline through Day 104

    The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• 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.

18 sites in 1 country: see every site and its status.