Screening and Baseline
Below is the schedule of assessments (SOA) for this stage of the study protocol (Protocol Amendment 02; 09 Jan 2025).
Visit 1 (Screening)
Some visits may be conducted over multiple days, where noted, for specific assessments.
Allowed interval: Up to 12 weeks prior to Day 1.
Participants may proceed to Day 1 as soon as all procedures are completed and eligibility has been reviewed.
- Informed consentℹ
- Inclusion and Exclusion Criteria
- Demographics
- Medical history
- Current medical conditions
- Concomitant medications
- SAE reviewℹ
- AE reviewℹ
- Vital signsℹ
- Physical Examinationℹ
- Viral Serologyℹ
- FSH and Estradiolℹ
- Tuberculosis (if suspected)ℹ
- Whole blood for genetic testing and APOE genotyping
- Thyroid function (TSH only)
- Vitamin B12 Levels and Folateℹ
- Coagulation panelℹ
- Amyloid Positivity Blood Testℹ
- Hematologyℹ
- Clinical chemistryℹ
Visit 2 (Screening)
Visits may be conducted over multiple days, where noted, for specific assessments.
Allowed interval: Up to 12 weeks prior to Day 1.
Participants may proceed to Day 1 as soon as all screening and baseline procedures are completed and do not necessarily have to use up to 12 weeks before Day 1. Baseline procedures must be completed before Day 1.
- Inclusion and Exclusion Criteria
- Concomitant medicationsℹ
Visit 3 (Screening)
Visits may be conducted over multiple days, where noted, for specific assessments.
Allowed interval: Up to 12 weeks prior to Day 1.
Participants may proceed to Day 1 as soon as all screening and baseline procedures are completed and do not necessarily have to use up to 12 weeks before Day 1. Baseline procedures must be completed before Day 1.
- Inclusion and Exclusion Criteria
- Concomitant medicationsℹ
- SAE reviewℹ
Visit 4 (Baseline)
Visits may be conducted over multiple days, where noted, for specific assessments.
Allowed interval: Up to 12 weeks prior to Day 1.
Participants may proceed to Day 1 as soon as all screening and baseline procedures are completed and do not necessarily have to use up to 12 weeks before Day 1. Baseline procedures must be completed before Day 1.
- Inclusion and Exclusion Criteria
- Medical history
- Current medical conditions
- Concomitant medications
- SAE reviewℹ
- AE reviewℹ
- Vital signsℹ
- Triplicate 12-Lead ECGℹ
- Physical Examinationℹ
- ADAS-Cog14 participantℹ
- ADCS-ADL-MCI study partnerℹ
- A-iADL study partner
- QOL-AD participantℹ
- QOL-AD study partner
- EQ-5D-3L participantℹ
Intervention Period
(number of weeks since treatment start)
Below is the schedule of assessments (SOA) for this stage of the study protocol.
Visit 5 (Day 1)
Participants may proceed to Day 1 as soon as all screening and baseline procedures are completed and do not necessarily have to use up to 12 weeks before Day 1. Baseline procedures must be completed before Day 1.
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
- Inclusion/exclusion criteria
- Randomization
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- Pregnancy Test (if applicable)ℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 6 (Week 4)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 7 (Week 8)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 8* (Week 12)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Pregnancy Test (if applicable)ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 9 (Week 16)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 10 (Week 20)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 11* (Week 24)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Pregnancy Test (if applicable)ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- CSF for exploratory analyses (for participants in CSF substudy)ℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 12 (Week 28)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 13 (Week 32)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 14 (Week 36)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 15 (Week 40)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 16 (Week 44)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 17* (Week 48)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 18* (Week 52)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Pregnancy Test (if applicable)ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 19 (Week 56)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 20 (Week 60)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- None
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 21 (Week 64)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 22 (Week 68)
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 23* (Week 72)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
Imaging
- None
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
Visit 24* (Week 76)
*Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
Allowed interval: +/- 7 days
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Pregnancy Test (if applicable)ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
- None
Early Treatment Discontinuation
Within 4 weeks post last dose.
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Pregnancy Test (if applicable)ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
- CSF for exploratory analyses (for participants in the CSF substudy)ℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
- None
Early Study Discontinuation
Within 4 weeks post last dose.
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
- None
Visit 25 (Follow-up)
Visit may be conducted over multiple days, such that the imaging and/or lumbar puncture procedures may be done on separate days, apart from the remaining assessments, with all procedures completed within the allowable visit window.
- Reassess consent capacity and burden to participant at least every 6 months. (Refer to Section 10.1.3 of the protocol.)
Examination, Vital signs & ECG
COAs/PROs and C-SSRS
- C-SSRS
Laboratory Assessments
- Urinalysis ℹ
- Hematology ℹ
- Clinical chemistryℹ
- Serum PK sample(s)ℹ
- Serum ADA Sample(s)ℹ
- Plasma samples for PD (e.g., PGRN)ℹ
- Plasma and Serum samples for PD and Exploratory biomarkersℹ
- Whole Blood PAXgene samples for Exploratory biomarkersℹ
- Whole Blood samples for PD and Exploratory biomarkersℹ
- Urine for exploratory biomarker analysesℹ
Imaging
Review
- Concomitant medications
- Radiation Exposure Reviewℹ
- AE review
- SAE review
Study Intervention Administration
- None
Table of Abbreviations
| Abbreviation | Definition |
|---|---|
| AD | Alzheimer's Disease |
| ADA | Antidrug antibody |
| ADAS-Cog | Alzheimer's Disease Assessment Scale-Cognitive Subscale |
| ADCS-ADL-MCI | Alzheimer's Disease Cooperative Study-Activities of Daily Living for MCI |
| AE | Adverse event |
| A-IADL | Amsterdam Instrumental Activities of Daily Living Questionnaire |
| ADCS-iADL | Alzheimer's Disease Cooperative Study – Instrumental Activities of Daily Living |
| APOE | Apolipoprotein E |
| BP | Blood pressure |
| CDR | Clinical Dementia Rating |
| CDR-GS | Clinical Dementia Rating-Global Score |
| CDR-SB | Clinical Dementia Rating Sum of Boxes |
| COA | Clinical outcome assessment |
| CSF | Cerebrospinal fluid |
| C-SSRS | Columbia Suicide Severity Rating Scale |
| CV | Cardiovascular |
| ECG | Electrocardiogram |
| EQ-5D-3L | European Quality of Life-5 Dimensions, 3 Level Version |
| FSH | Follicle stimulating hormone |
| GDS | Geriatric Depression Scale |
| ICF | Informed consent form |
| LLN | Lower limit of normal |
| LP | Lumbar puncture |
| MMSE | Mini-Mental State Exam |
| MRI | Magnetic resonance imaging |
| PCR | Polymerase chain reaction |
| PD | Pharmacodynamic |
| PET | Positron emission tomography |
| PGRN | Progranulin |
| PK | Pharmacokinetic |
| PRO | Patient-related outcomes |
| PT | Prothrombin time |
| QOL | Quality of Life |
| QOL-AD | Quality of Life in Alzheimer Disease |
| RNA | Ribonucleic acid |
| SAE | Serious adverse event |
| TSH | Thyroid stimulating hormone |
| WMS-IV LMI | Wechsler Memory Scale-IV Logical Memory I |
| WMS-IV LMII | Wechsler Memory Scale-IV Logical Memory II |
| WOCBP | Woman of childbearing potential |
| WONCBP | Woman of nonchildbearing potential |