A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04592341

Collaborator

(none)

192

Enrollment

Locations

Arm

59.8

Anticipated Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Gantenerumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

192 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Multicenter, Open-Label, Single Arm Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early (Prodromal to Mild) Alzheimer's Disease

Actual Study Start Date :

Nov 18, 2020

Anticipated Primary Completion Date :

Jul 27, 2023

Anticipated Study Completion Date :

Nov 13, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gantenerumab Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.	Drug: Gantenerumab Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

Arm

Intervention/Treatment

Experimental: Gantenerumab

Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.

Drug: Gantenerumab

Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

Outcome Measures

Primary Outcome Measures

Change from Baseline in Deposited Amyloid as Measured by Brain Amyloid PET Centiloid (CL) Levels [Up to Week 104]

Secondary Outcome Measures

Responses to Home Administration Questionnaire [Up to Week 208]
The home administration questionnaire will capture confidence, ease of use, convenience, and overall satisfaction.
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 224]
Change in the Columbia-Suicide Severity Rating Scale (C-SSRS) Score [Up to Week 208]
The C-SSRS is an assessment tool used to assess the lifetime suicidality of a patient (C-SSRS at baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual or potential lethality.
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [Up to Week 208]
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [Up to Week 208]
Percentage of Participants with Injection-Site Reactions (ISR) [24 hours after study drug administration, up to Week 208]
Injection reactions (local and systemic) are defined as adverse events that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
Percentage of Participants with Anti-Drug Antibodies to Gantenerumab [Up to Week 224]
Plasma Concentration of SC Gantenerumab at specified timepoints [Up to Week 224]
Change in Brain Amyloid Based on Different Dosing Frequency [Up to Week 208]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Probable Alzheimer's Disease (AD) dementia or prodromal AD.
Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.5.
If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.

Exclusion Criteria:

Any evidence of a condition other than AD that may affect cognition.
History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
History or presence of clinically evident cerebrovascular disease.
History or presence of posterior reversible encephalopathy syndrome.
History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
History of severe, clinically significant CNS trauma.
History or presence of intracranial mass that could potentially impair cognition.
Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
At risk for suicide in the opinion of the investigator.
Alcohol and/or substance abuse or dependants in past 2 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JEM Research LLC	Atlantis	Florida	United States	33462
2	ClinCloud, LLC	Maitland	Florida	United States	32751
3	Renstar Medical Research	Ocala	Florida	United States	34470
4	Alzheimer's Research and Treatment Center	Wellington	Florida	United States	33414
5	Center for Advanced Research & Education	Gainesville	Georgia	United States	30501
6	Summit Research Network Inc.	Portland	Oregon	United States	97210
7	Abington Neurological Associates Willow Grove	Willow Grove	Pennsylvania	United States	19090
8	Jessa Zkh (Campus Virga Jesse)	Hasselt		Belgium	3500
9	AZ Groeninge	Kortrijk		Belgium	8500
10	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
11	Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)	Bron cedex		France	69677
12	CH Pitie Salpetriere; IM2A	Paris		France	75651
13	Gerontopole; Centre de Recherche clinique	Toulouse		France	31059
14	Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin	Berlin		Germany	12200
15	ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic	Berlin		Germany	13125
16	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München		Germany	81675
17	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio	Italy	00186
18	Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia	Milano	Lombardia	Italy	20132
19	Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia - UO Malattie Neurodegenerative	Tricase (LE)	Puglia	Italy	73039
20	NZOZ Vitamed	Bydgoszcz		Poland	85-079
21	Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.	Lublin		Poland	20-016
22	Senior Sp. Z O.O. Poradnia Psychogeriatryczna	Sopot		Poland	81-855
23	Centrum Medyczne Euromedis Sp. z o.o.	Szczecin		Poland	70-111
24	Centrum Medyczne NeuroProtect	Warszawa		Poland	01-684
25	NZOZ WCA	Wrocław		Poland	53-659
26	Policlínica Guipuzcoa; Servicio de Neurología	Donostia-san Sebastian	Guipuzcoa	Spain	20014
27	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid	Spain	28223
28	Hospital Universitario de la Princesa; Servicio de Neurologia	Madrid		Spain	28006
29	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid		Spain	28041
30	Hospital Universitari i Politecnic La Fe; Servicio de Neurología	Valencia		Spain	46026
31	Re-Cognition	Birmingham		United Kingdom	B16 8QQ
32	Fritchie Centre	Cheltenham		United Kingdom	GL53 9DZ
33	Surrey and Borders NHS Foundation Trust; Brain Science Research Unit	Chertsey		United Kingdom	kt16 9au
34	Ninewells Hospital	Dundee		United Kingdom	DD12 9SY
35	Charing Cross Hospital; Imperial Memory Unit, Level 10 West	London		United Kingdom	W6 8RF

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04592341

Other Study ID Numbers:

WN29722
2020-001384-87

First Posted:

Oct 19, 2020

Last Update Posted:

Jun 27, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of Jun 27, 2022