Clincosm LogoSign in Get a demo

Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03443973
Collaborator
(none)
982
Enrollment
157
Locations
2
Arms
60
Anticipated Duration (Months)
6.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
982 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
Actual Study Start Date :
Aug 22, 2018
Anticipated Primary Completion Date :
Sep 21, 2022
Anticipated Study Completion Date :
Aug 23, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Gantenerumab

Gantenerumab will be administered as SC injections with gradual uptitration.

Drug: Gantenerumab
Gantenerumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • RO4909832

    		•
    Placebo Comparator: Placebo

    Placebo will be administered as SC injections with gradual uptitration.

    Drug: Placebo
    Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to Week 116 in Global Outcome, as Measured by Clinical Dementia Rating-Sum of Boxes (CDR-SOB) [Baseline up to Week 116]

    Secondary Outcome Measures

    1. Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score [Baseline up to Week 116]

    2. Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [Baseline up to Week 116]

    3. Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [Baseline up to Week 116]

    4. Change From Baseline to Week 116 in Verbal Fluency Task Score [Baseline up to Week 116]

    5. Change From Baseline to Week 116 in Coding [Change from baseline to Week 116 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest.]

    6. Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score [Baseline to Week 116]

    7. Change From Baseline to Week 116 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [Baseline up to Week 116]

    8. Percentage of Participants With Adverse Events (AEs) [Baseline up to end of study (week 164) or Week 35 (Open label extension)]

    9. Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [Baseline up to Week 116 or Week 24 in Open label extension]

    10. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [Baseline up to end of study (week 164) or Week 35 (Open label extension)]

    11. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [Baseline up to end of study (week 164) or Week 35 (Open label extension)]

    12. Percentage of Participants with Injection-Site Reactions [Baseline up to end of study (week 164) or Week 35 (Open label extension)]

    13. Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [Baseline up to end of study (week 164) or Week 35 (Open label extension)]

    14. Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 116 [Baseline up to Week 116]

    15. Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 116 [Baseline up to Week 116]

    16. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 116 [Baseline up to Week 116]

    17. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 116 [Baseline up to Week 116]

    Other Outcome Measures

    1. Plasma Concentration of Gantenerumab [Baseline, Week 2, 24, 41, 52, 76, 103, 115, 128, 164, and at early termination and unscheduled visit, Week 1 and Week 24 (Open label extension)]

      Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion criteria:

    • Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment)

    • Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid PET scan

    • Demonstrated abnormal memory function

    • MMSE score greater than or equal to 22 (≥ 22)

    • Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0

    • Availability of a reliable study partner who accepts to participate in study procedures throughout the 2 years duration of study

    • If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening and until randomization

    • For enrollment in the China extension, patients must have residence in mainland China, Hong Kong, or Taiwan and be of Chinese ancestry

    • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

    Key Exclusion criteria:

    • Any evidence of a condition other than AD that may affect cognition

    • History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder

    • 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 (e.g., glioma, meningioma) 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

    • At risk for suicide in the opinion of the investigator

    • Alcohol and/or substance abuse or dependants in past 2 years

    • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

    • Any contraindications to brain MRI

    • Unstable or clinically significant cardiovascular, kidney or liver disease

    • Uncontrolled hypertension

    • Unstable or clinically significant cardiovascular disease

    • Abnormal thyroid function

    • Patients with evidence of folic acid deficiency

    Exclusion for Open-Label Extension (OLE):

    • Discontinued from study treatment during the double-blind treatment period

    • Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment

    • Participation in the OLE deemed inappropriate by the investigator

    • Presence of ARIA-E findings at the Week 116 MRI scan

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    2 Barrow Neurological Institute Phoenix Arizona United States 85013
    3 Banner Sun Health Research Insitute Sun City Arizona United States 85351
    4 Health Initiatives Research, PLLC Fayetteville Arkansas United States 72703
    5 Fullerton Neurology and Headache Center Fullerton California United States 92835
    6 Neurology Center of North Orange County Fullerton California United States 92835
    7 Irvine Center for Clinical Research Irvine California United States 92614
    8 Desert Valley Research Redlands California United States 92374
    9 Southern California Research LLC Simi Valley California United States 93065
    10 Yale University School Of Medicine New Haven Connecticut United States 06519
    11 Georgetown University Medical Center Washington District of Columbia United States 20007
    12 Accel Research Sites - CRU Tampa Bradenton Florida United States 34201
    13 ClinCloud, LLC Maitland Florida United States 32751
    14 Optimus U Corp Miami Florida United States 33125
    15 Allied Biomedical Research Institute, Inc Miami Florida United States 33155
    16 Renstar Medical Research Ocala Florida United States 34470
    17 Progressive Medical Research Port Orange Florida United States 32127
    18 Intercoastal Medical Group Sarasota Florida United States 34239
    19 Infinity Clinical Research, LLC Sunrise Florida United States 33351
    20 Axiom Clinical Research of Florida Tampa Florida United States 33609
    21 Emory University Atlanta Georgia United States 30329
    22 Rush Alzheimer's Disease Cntr. Chicago Illinois United States 60612
    23 American Health Network Institute, LLC Avon Indiana United States 46123
    24 Brigham and Womens Hospital; Center for Alzheimer Research & Treatment Boston Massachusetts United States 02115
    25 ActivMed Practices and Research Haverhill Massachusetts United States 01830
    26 Boston Center for Memory Newton Massachusetts United States 02459
    27 Quest Research Institute Farmington Hills Michigan United States 48334
    28 Missouri Memory Center Bolivar Missouri United States 65613
    29 Washington University School of Medicine Saint Louis Missouri United States 63110
    30 University of Nebraska Medical Center; Dept of Neurological Sciences Omaha Nebraska United States 68198-8440
    31 Cleveland Clinic Lou Ruvo; Center for Brain Research Las Vegas Nevada United States 89106
    32 The Cognitive and Research Center of New Jersey Springfield New Jersey United States 07081
    33 AD-CARE, University of Rochester Medical Center Rochester New York United States 14620
    34 Richmond Behavioral Associates Staten Island New York United States 10314
    35 SUNY Upstate Medical University Syracuse New York United States 13210
    36 Behavioral Health Research Charlotte North Carolina United States 28211
    37 Alzheimer's Memory Center Matthews North Carolina United States 28105
    38 Raleigh Neurology Associates Raleigh North Carolina United States 27607-6520
    39 Wake Forest University Winston-Salem North Carolina United States 27157
    40 Neuro-Behavioral Clinical Research, Inc. Canton Ohio United States 44718
    41 Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health - Neurological Institute Cleveland Ohio United States 44195
    42 Lynn Health Science Institute Oklahoma City Oklahoma United States 73112
    43 Summit Research Network Inc. Portland Oregon United States 97210
    44 Texas Neurology PA Dallas Texas United States 75206
    45 Kerwin Medical Center Dallas Texas United States 75231
    46 Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine Houston Texas United States 77030
    47 The University of Texas Health Science Center at Houston Houston Texas United States 77054
    48 Hospital Italiano Buenos Aires Argentina C1181ACH
    49 Universidad Maimonides Caba Argentina C1405BCK
    50 Instituto Geriatrico Nuestra Señora de las Nieves Capital Federal Argentina C1427CCP
    51 CEN Centro Especializado en Neurociencias Cordoba Argentina X5004FJF
    52 Instituto Kremer Córdoba Argentina X5004AOA
    53 Instituto de Neurociencias San Agustín S.A. La Plata Argentina B1902AVF
    54 Fundacion Scherbovsky Mendoza Argentina M5500AYB
    55 AZ Sint Blasius (Dendermonde) Dendermonde Belgium 9200
    56 UZ Gent Gent Belgium 9000
    57 Jessa Zkh (Campus Virga Jesse) Hasselt Belgium 3500
    58 Psicomed Estudios Médicos Antofagasta Chile 1270244
    59 Biomedica Research Group Santiago Chile 7500710
    60 Especialidades Medicas LYS Santiago Chile 7560356
    61 Clinical Hospital Centre Zagreb;Clinic for Neurology Zagreb Croatia 10000
    62 Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken Aarhus N Denmark 8200
    63 Rigshospitalet, Hukommelsesklinikken Koebenhavn Oe Denmark 2100
    64 Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn Svendborg Denmark 5700
    65 Terveystalo Ruoholahti Helsinki Finland 00180
    66 University of Eastern Finland Kuopio Finland 70210
    67 Yachiyo Hospital Aichi Japan 446-8510
    68 Nagoya Ekisaikai Hospital Aichi Japan 454-8502
    69 National Center for Geriatrics and Gerontology Aichi Japan 474-8511
    70 Fukuoka University Hospital Fukuoka Japan 814-0180
    71 National Hospital Organization Hiroshima-Nishi Medical Center Hiroshima Japan 739-0696
    72 Kobe University Hospital Hyogo Japan 650-0017
    73 Hyogo Prefectural HarimaHimeji General Medical Center Hyogo Japan 670-8560
    74 Tsukazaki Hospital Hyogo Japan 671-1227
    75 Matsui Dietary and Dementia Clinic Hyogo Japan 673-0891
    76 Kagawa Prefectural Central Hospital Kagawa Japan 760-8557
    77 Rakuwakai Otowa Hospital Kyoto Japan 607-8062
    78 Uji Takeda Hospital Kyoto Japan 611-0021
    79 Okayama Kyokuto Hospital Okayama Japan 703-8265
    80 Rijikai Medical Corporation Katayama Medical Clinic Okayama Japan 710-0813
    81 MI Clinic Osaka Japan 560-0004
    82 Kishiwada Tokushukai Hospital Osaka Japan 596-0042
    83 National Hospital Organization Hizen Psychiatric Medical Center Saga Japan 842-0192
    84 Medical corporation Ichiekai Itsuki Hospital Tokushima Japan 770-0852
    85 Tokushima Hospital Tokushima Japan 776-8585
    86 Dong-A University Hospital Busan Korea, Republic of 49201
    87 Myongji Hospital Gyeonggi-do Korea, Republic of 10475
    88 Gachon University Gil Medical Center Incheon Korea, Republic of 21565
    89 Inha University Hospital Incheon Korea, Republic of 22332
    90 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    91 Hanyang University Seoul Hospital Seoul Korea, Republic of 04763
    92 Konkuk University Medical Center Seoul Korea, Republic of 05030
    93 Asan Medical Center Seoul Korea, Republic of 05505
    94 Samsung Medical Center Seoul Korea, Republic of 06351
    95 Seoul St Mary's Hospital Seoul Korea, Republic of 06591
    96 Ewha Womans University Hospital (Seoul) Seoul Korea, Republic of 07804
    97 Ewha Womans University Mokdong Hospital Seoul Korea, Republic of 07985
    98 Mexico Centre for Clinical Research Ciudad de México Mexico CITY (federal District) Mexico 03100
    99 Hospital Angeles Culiacan; Neurociencias Culiacan Mexico 80020
    100 Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta Monterrey Mexico 64460
    101 AVIX Investigación Clínica S.C Monterrey Mexico 64710
    102 Brain Research Center B.V Amsterdam Netherlands 1081 GN
    103 Podlaskie Centrum Psychogeriatrii Białystok Poland 15-756
    104 NZOZ Vitamed Bydgoszcz Poland 85-079
    105 KO-MED Centra Kliniczne Lublin II Lublin Poland 20-362
    106 Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych Plewiska Poland 62-064
    107 NEURO-CARE Sp. z o.o. Sp. Komandytowa Siemianowice Śląskie Poland 41-100
    108 Senior Sp. Z O.O. Poradnia Psychogeriatryczna Sopot Poland 81-855
    109 mMED Maciej Czarnecki Warszawa Poland 01-684
    110 Pratia S.A. Warszawa Poland 01-868
    111 NZOZ WCA Wrocław Poland 53-659
    112 Ośrodek Badawczo-Naukowo-Dydaktyczny Chorób Otępiennych w Ścinawie Ścinawa Poland 59-330
    113 Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia Amadora Portugal 2720-276
    114 Hospital de Braga; Servico de Neurologia Braga Portugal 4710-243
    115 HUC; Servico de Neurologia Coimbra Portugal 3000-075
    116 Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia Guimarães Portugal
    117 Hospital Geral de Santo Antonio; Servico de Neurologia Porto Portugal 4099-001
    118 Santa Cruz Behavioral PSC Bayamon Puerto Rico 00961
    119 University of Puerto Rico - Medical Science Campus; Internal Medicine San Juan Puerto Rico 00936
    120 National University Hospital (NUH); Neuroscience Singapore Singapore 117549
    121 National Neuroscience Institute; Neurology Singapore Singapore 308433
    122 Hospital General Universitario de Elche; Servicio de Neurología Elche Alicante Spain 03203
    123 Hospital Mutua De Terrasa; Servicio de Neurologia Terrassa Barcelona Spain 08222
    124 Hospital Virgen del Puerto. Servicio de Neurología Plasencia Caceres Spain 10600
    125 Policlínica Guipuzcoa; Servicio de Neurología Donostia-san Sebastian Guipuzcoa Spain 20014
    126 Hospital Universitario de Santa Maria; Servicio de Neurología Lleida Lerida Spain 25198
    127 Hospital Quiron de Madrid; Servicio de Neurologia Pozuelo de Alarcon Madrid Spain 28223
    128 Clinica Universitaria de Navarra; Servicio de Neurología Pamplona Navarra Spain 31008
    129 Clinica Universitaria de Navarra Pamplona Navarra Spain 31008
    130 CAE OROITU; Servicio de Neurología Getxo Vizcaya Spain 48993
    131 Hospital del Mar; Servicio de Neurologia Barcelona Spain 08003
    132 Fundación ACE; Servicio de Neurología Barcelona Spain 08028
    133 Universitario de La Princesa; Servicio de Neurología Madrid Spain 28006
    134 Hospital Victoria Eugenia; Servico Neurología Sevilla Spain
    135 Hospital Universitario la Fe; Servicio de Neurologia Valencia Spain 46026
    136 Complejo Asistencial de Zamora; Servicio Psiquiatria Zamora Spain 49021
    137 Skånes Universitetssjukhus Malmö, Minneskliniken Malmö Sweden 211 46
    138 Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry Mölndal Sweden 431 41
    139 KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54 Stockholm Sweden 141 86
    140 Istanbul University Istanbul School of Medicine; Neurology Istanbul Turkey 34093
    141 Bezmialem Vakif Univ Medical Istanbul Turkey 34286
    142 Ondokuz Mayis Univ. Med. Fac.; Neurology Samsun Turkey 55139
    143 The Rice Centre; Royal United Hospital Bath United Kingdom BA1 3NG
    144 Re-Cognition Birmingham United Kingdom B16 8QQ
    145 The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre Cheltenham United Kingdom GL53 9DZ
    146 Surrey and Borders NHS Foundation Trust; Brain Science Research Unit Chertsey United Kingdom kt16 9au
    147 Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit Crowborough United Kingdom TN6 1HB
    148 Ninewells Hospital Dundee United Kingdom DD12 9SY
    149 Queen Elizabeth University Hospital; Clinical Research Facility Glasgow United Kingdom G51 4TF
    150 St George's Hospital London United Kingdom SW17 0QT
    151 RE:Cognition Health London United Kingdom W1G 9RU
    152 Charing Cross Hospital London United Kingdom W6 8RF
    153 Campus for Ageing and Vitality Newcastle United Kingdom NE4 5PL
    154 John Radcliffe Hospital Oxford United Kingdom OX3 9DU
    155 Royal Preston Hospital Preston United Kingdom PR2 9HT
    156 Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust Sheffield United Kingdom S10 2JF
    157 University Southampton NHS Foundation Trust; Wessex Neurologica Centre Southampton United Kingdom SO166YD

    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:
    NCT03443973
    Other Study ID Numbers:
    • WN39658
    • 2017-001365-24
    First Posted:
    Feb 23, 2018
    Last Update Posted:
    Jul 6, 2022
    Last Verified:
    Jul 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:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    No Results Posted as of Jul 6, 2022