Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer's Disease on Donepezil: MINDSET Study

A Phase 3, Double-blind, Randomized Study of RVT-101 Versus Placebo When Added to Existing Stable Donepezil Treatment in Subjects With Mild to Moderate Alzheimer's Disease

This study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) as an adjunctive therapy to donepezil for the treatment of subjects with Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: RVT-101; Drug: Placebo

Detailed Description

This Phase 3 study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) on both cognition and activities of daily living when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease after 24 weeks of double-blind treatment. This study will also provide further information on the safety and tolerability of the 35-mg dose of intepirdine (RVT-101) when used in combination with donepezil compared to donepezil alone. This study is being conducted under the agreement of a Special Protocol Assessment by FDA. Subjects completing this study will be eligible to enroll in a 12 month open-label study of RVT-101 (RVT-101-3002) in which concomitant medications for the treatment of Alzheimer's disease including memantine will be allowed.

• Study Type: Interventional
• Enrollment (Actual): 1315
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1828CKR
    • AR101
  • Buenos Aires, Argentina, C1199ABB
    • AR060
  • Ciudad Autónoma de Buenos Aire, Argentina, C1405BCK
    • AR040
  • Ciudad Autónoma de Buenos Aire, Argentina, C1425AHQ
    • AR081
  • Ciudad Autónoma de Buenos Aire, Argentina, C1012AAR
    • AR084
  • Ciudad Autónoma de Buenos Aire, Argentina, C1058AAJ
    • AR027
  • Ciudad Autónoma de Buenos Aire, Argentina, C1111AAL
    • AR012
  • Ciudad Autónoma de Buenos Aire, Argentina, C1117ABH
    • AR160
  • Ciudad Autónoma de Buenos Aire, Argentina, C1406BOA
    • AR028
  • Ciudad Autónoma de Buenos Aire, Argentina, C1428AQK
    • AR035
  • Cordoba, Argentina, X5000DCE
    • AR051
  • Cordoba, Argentina, X5000FJF
    • AR137
  • Mendoza, Argentina, M5501ACP
    • AR210
  • Mendoza, Argentina, M5502AHV
    • AR219
  • Santiago del Estero, Argentina, G4200DND
    • AR059
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, A1902AJU
      • AR130
    • La Plata, Buenos Aires, Argentina, B1900BOM
      • AR041
• Australia
  • Caulfield, Australia, VIC3162
    • AU227
  • Chermside, Australia, QLD 4032
    • AU079
  • Heidelberg West, Australia, VIC 3081
    • AU032
  • Herston, Australia, QLD 4209
    • AU062
  • Hornsby, Australia, NSW 2077
    • AU011
  • West Perth, Australia, WA 6005
    • AU138
• Bulgaria
  • Ruse, Bulgaria, 7003
    • BU125
  • Sofia, Bulgaria, 1431
    • BU131
  • Sofia, Bulgaria, 1632
    • BU198
  • Varna, Bulgaria, 9000
    • BU073
• Canada
  • Alberta
    • Medicine Hat, Alberta, Canada, T1B4E7
      • CA151
  • British Columbia
    • Kamloops, British Columbia, Canada, V2C 1K7
      • CA120
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • CA054
    • Kelowna, British Columbia, Canada, V1Y 4N7
      • CA188
    • Penticton, British Columbia, Canada, V2A 5C8
      • CA186
    • West Vancouver, British Columbia, Canada, V7T 2Z3
      • CA141
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 5G8
      • CA147
    • North York, Ontario, Canada, M3B 2S7
      • CA196
    • Toronto, Ontario, Canada, M4G 0A1
      • CA237
  • Quebec
    • Gatineau, Quebec, Canada, J8T8JI
      • CA236
• Chile
  • II Región
    • Antofagasta, II Región, Chile, 1270244
      • CH212
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7560356
      • CH076
  • Región Metropolitana
    • Santiago, Región Metropolitana, Chile, 7510186
      • CH061
    • Santiago, Región Metropolitana, Chile, 7520338
      • CH075
• Croatia
  • Zagreb, Croatia, 10000
    • CR069
  • Zagreb, Croatia, 10000
    • CR122
  • Zagreb, Croatia, 10090
    • CR070
  • Zagreb, Croatia, 10090
    • CR068
  • Zagreb, Croatia, 10090
    • CR083
• Czechia
  • Praha 10, Czechia, 100 00
    • CZ128
  • Praha 10, Czechia, 109 00
    • CZ207
  • Praha 2, Czechia, 120 00
    • CZ132
  • Praha 6, Czechia, 160 00
    • CZ129
  • Rychnov nad Kneznou, Czechia, 516 01
    • CZ161
• France
  • Lille Cedex, France, 59037
    • FR231
  • Marseille Cedex 5, France, 13385
    • FR182
  • Paris Cedex, France, 75013
    • FR221
  • Villeurbanne, France, 69 100
    • FR202
• Germany
  • Bad Homburg, Germany, 61348
    • GE206
  • Berlin, Germany, 10117
    • GE091
  • Berlin, Germany, 12203
    • GE071
  • Berlin, Germany, 13125
    • GE139
  • Cologne, Germany, 50937
    • GE230
  • Ellwangen, Germany, 73479
    • GE252
  • Leipzig, Germany, 04107
    • GE180
  • Mannheim, Germany, 68165
    • GE228
  • Munchen, Germany, 81675
    • GE017
  • Nürnberg, Germany, 90402
    • GE157
  • Ulm, Germany, 89081
    • GE098
  • Westerstede, Germany, 26655
    • GE251
• Italy
  • Brescia, Italy, 25125
    • IT053
  • Cefalù, Italy, 90015
    • IT124
  • Pavia, Italy, 27100
    • IT030
  • Perugia, Italy, 06156
    • IT103
  • Roma, Italy, 00168
    • IT072
  • Roma, Italy, 00189
    • IT029
  • Roma, Italy, 00179
    • IT183
  • Rome, Italy, 00185
    • IT175
  • Torino, Italy, 10 126
    • IT085
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • SK066
  • Seoul, Korea, Republic of, 06351
    • SK067
  • Seoul, Korea, Republic of, 07061
    • SK190
• Poland
  • Bialystok, Poland, 15-756
    • PO013
  • Bydgoszcz, Poland, 85-080
    • PO024
  • Bydgoszcz, Poland, 85-796
    • PO010
  • Katowice, Poland, 40-123
    • PO107
  • Katowice, Poland, 40-749
    • PO092
  • Krakow, Poland, 30-349
    • PO023
  • Krakow, Poland, 35-505
    • PO025
  • Poznan, Poland, 61-853
    • PO009
  • Szczecin, Poland, 70-111
    • PO014
  • Warszawa, Poland, 01-697
    • PO074
• Serbia
  • Belgrade, Serbia, 11 000
    • SE164
  • Belgrade, Serbia, 11000
    • SE090
  • Belgrade, Serbia, 11000
    • SE166
  • Belgrade, Serbia, 11000
    • SE193
  • Kragujevac, Serbia, 34000
    • SE155
  • Novi Knezevac, Serbia, 23330
    • SE031
  • Vrsac, Serbia, 26300
    • SE165
• Singapore
  • Singapore, Singapore, 119074
    • SI052
  • Singapore, Singapore, 308433
    • SI026
• Slovakia
  • Banska Bystrica, Slovakia, 97404
    • SL056
  • Bratislava, Slovakia, 820 07
    • SL192
  • Dubnica nad Váhom, Slovakia, 01841
    • SL200
  • Kosice, Slovakia, 040 17
    • SL191
  • Krompachy, Slovakia, 05342
    • SL078
  • Svidnik, Slovakia, 08901
    • SL077
• Spain
  • Alicante, Spain, 03690
    • SP249
  • Barcelona, Spain, 08003
    • SP176
  • Barcelona, Spain, 08028
    • SP022
  • Barcelona, Spain, 08035
    • SP021
  • Barcelona, Spain, 08036
    • SP250
  • Ceuta, Spain, 51003
    • SP019
  • Donostia, Spain, 20014
    • SP194
  • Getxo, Spain, 48993
    • SP222
  • Madrid, Spain, 28040
    • SP018
  • Madrid, Spain, 28046
    • SP093
  • Sant Cugat del Vallès, Spain, 08190
    • SP184
  • Terrassa, Spain, 08221
    • SP020
• Taiwan
  • Kaohsiung, Taiwan, 833
    • TA065
  • Taipei, Taiwan, 100
    • TA086
  • Taoyuan, Taiwan, 333
    • TA121
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • UK063
  • Blackpool, United Kingdom, FY2 0JH
    • UK038
  • Cambridge, United Kingdom, CB21 5EF
    • UK233
  • Cannock, United Kingdom, WS11 0BN
    • UK033
  • Epping, United Kingdom, CM16 6TN
    • UK211
  • Guildford, United Kingdom, GU2 7YD
    • UK234
  • Leeds, United Kingdom, LS10 1DU
    • UK055
  • London, United Kingdom, W1G 9JF
    • UK039
  • Manchester, United Kingdom, M13 9NQ
    • UK034
  • Norwich, United Kingdom, NR2 3TD
    • UK229
  • Oxford, United Kingdom, OX3 9DU
    • UK087
  • Plymouth, United Kingdom, PL5 8BT
    • UK235
  • Sheffield, United Kingdom, S5 7JT
    • UK100
  • Southampton, United Kingdom, SO16 6YD
    • UK064
  • Southampton, United Kingdom, SO30 3JB
    • UK152
  • Swindon, United Kingdom, SN3 6BW
    • UK153
  • Warrington, United Kingdom, WA22 8WA
    • UK154
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85005
      • US112
    • Tucson, Arizona, United States, 85704
      • US220
  • California
    • Encino, California, United States, 91436
      • US168
    • Fullerton, California, United States, 92835
      • US117
    • Los Angeles, California, United States, 90024
      • US214
    • Pasadena, California, United States, 91105
      • US189
    • Rancho Mirage, California, United States, 92270
      • US096
    • Santa Ana, California, United States, 92705
      • US0195
    • Simi Valley, California, United States, 93065
      • US016
    • Temecula, California, United States, 92591
      • US106
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • US179
    • Norwich, Connecticut, United States, 06360
      • US171
  • Florida
    • Atlantis, Florida, United States, 33462
      • US088
    • Brooksville, Florida, United States, 34601
      • US007
    • Hallandale Beach, Florida, United States, 33009
      • US002
    • Hialeah, Florida, United States, 33012
      • US140
    • Miami, Florida, United States, 33137
      • US216
    • Miami, Florida, United States, 33165
      • US110
    • North Palm Beach, Florida, United States, 33408
      • US172
    • Orlando, Florida, United States, 32806
      • US003
    • Pensacola, Florida, United States, 32502
      • US256
    • Tampa, Florida, United States, 33613
      • US037
    • Tampa, Florida, United States, 33613
      • US042
    • The Villages, Florida, United States, 32162
      • US004
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • US048
    • Atlanta, Georgia, United States, 30342
      • US046
    • Columbus, Georgia, United States, 31909
      • US217
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • US111
    • Shreveport, Louisiana, United States, 71104
      • US095
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • US116
    • Quincy, Massachusetts, United States, 02169
      • US174
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • US144
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • US094
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • US135
    • Lawrenceville, New Jersey, United States, 08648
      • US197
    • Manchester, New Jersey, United States, 08759
      • US057
    • Mount Arlington, New Jersey, United States, 07856
      • US215
    • Toms River, New Jersey, United States, 08755
      • US209
    • West Long Branch, New Jersey, United States, 07764
      • US036
  • New York
    • Albany, New York, United States, 12208
      • US001
    • Brooklyn, New York, United States, 11235
      • US049
    • New Hyde Park, New York, United States, 11040
      • US097
    • New Windsor, New York, United States, 12553
      • US177
    • New York, New York, United States, 10022
      • US044
    • New York, New York, United States, 10021
      • US142
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • US150
    • Charlotte, North Carolina, United States, 28270
      • US185
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • US113
    • Cincinnati, Ohio, United States, 45227
      • US008
    • Cincinnati, Ohio, United States, 45220
      • US136
    • Shaker Heights, Ohio, United States, 44122
      • US119
  • Oregon
    • Portland, Oregon, United States, 97210
      • US134
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • US169
    • Philadelphia, Pennsylvania, United States, 19102
      • US187
    • Plains, Pennsylvania, United States, 18075
      • US162
    • Willow Grove, Pennsylvania, United States, 19001
      • US148
  • Texas
    • Houston, Texas, United States, 77074
      • US115
    • San Antonio, Texas, United States, 78229
      • US043
  • Utah
    • Orem, Utah, United States, 84058
      • US143
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • US149
  • Washington
    • Spokane, Washington, United States, 99202
      • US170

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject with AD
• Ongoing donepezil therapy for AD
• An MMSE score 12 to 24 inclusive at Screening; MMSE score 10-26 inclusive at Baseline
• Hachinski Ischaemia score less than or equal to 4 at Screening.
• If female, subject must be: a. of non-childbearing potential or surgically sterile; or, b. willing to use an adequate methods of birth control. Male subjects who are sexually active will also be required to use an adequate form of birth control.
• Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator.
• Subject has a reliable caregiver who is willing to report on subject's status throughout the study.

Exclusion Criteria:

Other Causes for Dementia

• Diagnosis of vascular dementia
• Atypical clinical features or clinical course of dementia that would lead the investigator to conclude symptoms are more likely due to an alternate dementia diagnosis including, but not limited to, frontotemporal dementia, Lewy body dementia, or others.

Confounding Medical Conditions

• History of significant psychiatric illness such as schizophrenia or bipolar affective disorder or any other significant psychiatric illness that in the opinion of the investigator would interfere with participation in the study;
• Any clinically relevant concomitant disease, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RVT-101; RVT-101 adjunct to 5 mg or 10 mg donepezil	Drug: RVT-101; once daily, oral, 35 mg tablets
Placebo Comparator: Placebo; Placebo adjunct to 5 mg or 10 mg donepezil	Drug: Placebo; once daily, oral, pill manufactured to match RVT-101 35 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24	The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.	Baseline, 24 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24	The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function	Baseline, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24	The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function	24 weeks
The Dependence Scale (DS) Score Change From Baseline to Week 24	The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency.	Baseline, 24 weeks
Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24	The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined.	Baseline and Week 24
ADAS-Cog-13 Score Change From Baseline to Week 24	13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.	Baseline, 24 weeks
Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma	Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24	Week 6, Week 12, Week 18, Week 24

Collaborators and Investigators

• Sponsor: Axovant Sciences Ltd.
• Investigators: Study Director: Ilise Lombardo, MD, Axovant Sciences, Inc., Vice President, Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: October 22, 2015
• First Submitted That Met QC Criteria: October 22, 2015
• First Posted (Estimate): October 26, 2015

Study Record Updates

• Last Update Posted (Actual): December 5, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: dementia; Alzheimer's disease; RVT-101; donepezil; intepirdine
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: RVT-101-3001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No