PATIENT AND CAREGIVER EXPERIENCE IN PHASE III TRIALS OF GANTENERUMAB IN EARLY ALZHEIMER'S DISEASE: QUALITATIVE SURVEY RATIONALE AND DESIGN - Medically
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PATIENT AND CAREGIVER EXPERIENCE
IN PHASE III TRIALS OF GANTENERUMAB
IN EARLY ALZHEIMER’S DISEASE:
QUALITATIVE SURVEY RATIONALE AND DESIGN
Alberto Villarejo-Galende, PhD1; Christine D. Pozniak, PhD2; Fiona McDougall, PhD2; Sheila Seleri Assunção, MD, PhD3;
Wael Abouelkheir, MBA2; Beverly Assman, MSc3; Rozanno Gonzales, MS3; Oliver Peters, MD4; David Watson, PsyD, CPI5
1Hospital
Universitario 12 de Octubre, Madrid, Spain; 2F. Hoffmann-La Roche/Genentech, Basel, Switzerland; 3Genentech, A Member of the Roche Group, South
San Francisco, CA, USA; 4Charité - Universitätsmedizin Berlin and DANE Berlin, Berlin, Germany; 5Alzheimer's Research and Treatment Center, Wellington, FL, USADisclosures
• Alberto Villarejo-Galende is a consultant for Roche; is • Sheila Seleri Assunção, Beverly Assman, and
on a speaker bureau for KRKA, Esteve, Roche, KERN Rozanno Gonzales are full-time employees of Genentech
Pharma, and Neuraxpharm; and received research support Inc., a member of the Roche Group.
for clinical trials with AbbVie, Eisai, Roche, TauRx, Novo
Nordisk, and Araclon-Grifols. • Oliver Peters is a consultant for Roche, Biogen, Griffols,
• Christine D. Pozniak was a full-time employee of F. and Advantage; is on a speaker bureau for Schwabe; and
Hoffmann-La Roche Ltd. at the time that this study was received research support from Biogen, Eisai, Janssen,
designed. Genentech, Lilly, Novartis, Pharmatrophix, Probiodrug, and
Roche.
• Fiona McDougall and Wael Abouelkheir are full-time
employees of F. Hoffmann-La Roche Ltd.
• David Watson is a national PI for F. Hoffmann-La Roche
Ltd., and Genentech Inc., a member of the Roche Group.
2Understanding the Patient and Caregiver Experience with
Gantenerumab, A Potential Disease-Modifying Therapy for AD
Identifying treatment burdens and potential solutions associated with DMT use in a
real-world setting could improve their accessibility, patient adherence to treatment
and, consequently, patient outcome
Given the importance of their input in clinical research, a survey of patient and
study partner (care partner) experiences is being conducted in the Phase 3
program of gantenerumab in early AD
Gantenerumab is a fully human IgG1 monoclonal antibody for subcutaneous
administration that promotes Fcγ receptor-mediated microglial phagocytosis of
aggregated Aβ1,2 and that is under investigation in early AD (GRADUATE I and II)3,4
and familial AD (DIAN-TU)5,6
Aβ, beta-amyloid; AD, Alzheimer’s disease.
1. Bohrmann B, et al. J Alzheimers Dis. 2012;28:49-69. 2. Ostrowitzki S, et al. Alzheimer’s Res Ther. 2017;9:95. 3. ClinicalTrials.gov. NCT03444870. https://clinicaltrials.gov/ct2/show/NCT03444870.
Accessed March 3, 2022. 4. ClinicalTrials.gov. NCT03443973. https://clinicaltrials.gov/ct2/show/NCT03443973. Accessed March 3, 2022. 5. ClinicalTrials.gov. NCT04623242. 3
https://clinicaltrials.gov/ct2/show/NCT04623242. Accessed March 3, 2022. 6. ClinicalTrials.gov. NCT01760005. https://clinicaltrials.gov/ct2/show/NCT01760005. Accessed March 3, 2022.Gantenerumab Phase 3 GRADUATE I AND GRADUATE II Studies
Two parallel, Phase 3, global, randomized placebo-controlled studies of gantenerumab
in early Alzheimer’s disease1-7
Studies ongoing in
31 countries
Includes option for home administration
N=985 (GRADUATE I)
N=981 (GRADUATE II) Gantenerumab subcutaneous
Expected completion Q4 2022 injections
dose titration to 510 mg every 2 weeks
Key Inclusion Criteria R Post-
• Age 50 to 90 years Screening 1:1 Placebo subcutaneous injections GRADUATE
up to Open-Label
• Early (prodromal or mild) AD: 12 weeks Extension
○ Clinical diagnostic criteriaa
○ Confirmed Aβ pathology by 120 mg Q4W x 3 months, 116
255 mg Q4W x 3 months,
CSF or PET scan 510 mg Q4W x 3 months
weeks
○ MMSE score ≥22
○ CDR-GS=0.5 or 1 Long-term
Universal 9-month dose titration
○ Amnestic deficits (FCSRT)b follow-up
regardless of APOE ε4 allele status Week 128c, 164c
○ Any APOE ε4 allele status
Primary Endpoint: Key Secondary Efficacy Endpoints: ADAS-Cog13, MMSE, Verbal Fluency, ADCS-ADL, FAQ
Clinical Dementia Rating-Sum of Additional Endpoints: CSF biomarkers, Amyloid and tau PET, MRI, plasma biomarkers, safety
Boxes (CDR-SB)
Studies WN39658 and WN29922. AD, Alzheimer’s disease; ADAS-Cog13,13-item Alzheimer’s Disease Assessment Scale–Cognitive Subscale; ADCS-ADL, Alzheimer Disease Cooperative Study–Activities of Daily Living; CDR-GS, Clinical Dementia Rating-Global Score;
CSF, cerebrospinal fluid; FAQ, Functional Activities Questionnaire; MMSE, Mini-Mental State Examination; OLE, MRI, Magnetic Resonance Imagin; open-label extension; PET, positron emission tomography; R, randomized
aProbable AD dementia (consistent with NIA/AA core clinical criteria for probable AD dementia) or prodromal AD (consistent with the NIA/AA diagnostic criteria and guidelines for MCI due to AD). bThe inclusion criteria for FCSRT was Free recall ≤ 27 and Cueing index ≤
0.67. cGRADUATE studies could be extended to 30 months in total, in the event that COVID-19-related interruptions in dosing and other study procedures worsen significantly.
1. Roche Investor Report. Available at: www.roche.com/investors.htm. Accessed July 22, 2021. 2. NIH. Available at: NCT03443973. Accessed July 22, 2021. 3. NIH. Available at: NCT03444870. Accessed July 22, 2021. 4. NIH. Available at: NCT04374253. Accessed
August 11, 2021. 5. Lane C, et al. Oral Presentation Presented at Clinical Trials on Alzheimer’s Disease 2021, Boston, MA; November 9-12, 2021. 6. Pross N, et al. Presented at AD/PD 2019, March 26–31, Lisbon, Portugal; 7. Data on file. 4Patient and Study Partner Experience: Qualitative Surveya
Patients completing the
double-blind phase of the Semi-structured 60-minute interview
GRADUATE studies or those with patients and study partners
with early termination
Participants eligible for this substudy must:
Inclusion • Have participated in GRADUATE I or II studies
Criteria • Have the ability to provide informed consent and take part in a 60-minute interview
• Have completed their last GRADUATE study visit or have withdrawn or discontinued from GRADUATE 1 or 2b
1. Assess patients’ and study partners’ experience while participating in GRADUATE trials
Objectives 2. Identify common challenges expected to be seen in the real world
3. Identify possible solutions to mitigate challenges and optimize the patient/study partner treatment journey
• Enrolling up to 100 pairs of patients and their study partners
• Interviews conducted up to 8 weeks after the final GRADUATE study visit or up to 4 weeks after early
Design withdrawal/discontinuation
• Patient and study partner interviews conducted separately
• Interviews take place via video or phone
aStudy participants will mainly be recruited in pairs. However, in limited instances, individual study patients or caregivers of patients who are unable to participate in an interview will be invited to be interviewed individually.
bPatients or caregivers who withdrew or discontinued from GRADUATE I or II and are part of the long-term safety follow-up study will be excluded.
No additional treatments or procedures will be required during a patient’s enrollment in GRADUATE I or II or POST-GRADUATE studies.
Data on file, Genentech, Inc.
5Patient and Study Partner Experience Survey and Interview Guides
Development included input from AD experts, and patients and caregivers
Development of the Survey Key Takeaways from
and Interview Guides Pilot Interviews
An advisory board was conducted to collect Terminology and treatment-related concepts
input from AD experts on the design of the were clear and understood
qualitative survey and interview guides
Gaps in priority concepts included questions
Pilot interviews conducted with 10 patients and related to:
care partners of individuals with AD
• Treatment burden for patients and study partners
• Assessed the validity of concepts
• Understanding how to improve comfort around
• Identified gaps in priority concepts home injections
• Confirmed participants’ understanding of • Personalizing the patient treatment experience
terminology, disease, treatment-related concepts,
and the language used in the interview guides
AD, Alzheimer’s disease.
Data on file, Genentech, Inc. 6Overview of Final Interview Guide
Total of 28 Questions, Approximately 60 Minutes
Section Title Section Summary
Experience of study visits, including procedures, assessments, PET and MRI
scans, positive aspects of study participation, stressful/burdensome elements of
Study Experience study participation
e.g. How was your experience with the MRI scan?
Did you find any elements of the study stressful/burdensome?
Experience with treatment administered as subcutaneous injection, future
potential options (treatment administered by caregiver at home), current tools,
Treatment Experience
aids, or technology used to monitor symptoms
e.g. How do you feel about receiving treatment via subcutaneous injection?
GRADUATE Study Motivations for taking part in the GRADUATE study, expectations of the
Motivations and GRADUATE study, study information, attitudes about future treatment options.
Expectations e.g. What were your motivations for taking part in the GRADUATE study?
MRI, magnetic resonance imaging; PET, positron emission tomography.
Data on file, Genentech, Inc. 7Planned Data Analyses
Qualitative assessment of patient and study partner experiences
• Survey participant characteristics will be summarized based on GRADUATE studies I and II
and will include:
Sociodemographic data
Clinical characteristics
Outcome measure scores
• Patients’ and study partners’ descriptions of their clinical trial experiences, treatment
experiences, and treatment preferences will be analyzed to identify emerging themes
and concepts
• Data collected during the GRADUATE studies will be used to define subgroups for
qualitative analysis
Data on file, Genentech, Inc. 8Timeline for Patient-Caregiver Study Experience Work
Pilot
Recruitment End of Data Communication
Study
Period Interviews Analysis of Results
Interviews
April – May 2021 Sep 2021 – Oct 2022 Oct 2022 Nov 2022 – Q1 2023 Q2-2023
Data on file, Genentech, Inc. 9Participating Countries
CANADA
SPAIN
UNITED
STATES
AUSTRALIA
Active
Projected
Data on file, Genentech, Inc.
10Limitations
Potential perception of greater burden due to several procedures included in clinical trials
that are not routinely conducted in clinical practice
Paradoxically, potential reduced perception of burden due to participation in a clinical trial
in which greater support is present
Recall bias due to the long time between being randomized into GRADUATE program and
time of interview
Potential patient selection bias towards earlier/less severe disease or those with more
positive trial experiences, given eligibility criteria require participation in GRADUATE I or II
along with retained ability to provide informed consent and participate in an interview
AD, Alzheimer’s disease.
Data on file, Genentech, Inc. 11Summary
Patient and caregiver experiences are crucial to informing the development of novel
AD treatments
Qualitative surveys administered to patients and their study partners in GRADUATE
studies will help identify barriers and facilitators to treatment with gantenerumab
These surveys are ongoing and data will be available in 2023
Data on file, Genentech, Inc. 12Acknowledgements
We would like to thank all the patients and their families,
the investigators and site staff, and the entire study team for
their time and commitment to the GRADUATE studies.
This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Medical writing and editorial support in the development of this presentation were provided by
Taylor Clark, PhD; Steve Candela, PhD; and Clare Sonntag, MA, of Health & Wellness Partners,
LLC, funded by F. Hoffmann-La Roche Ltd.
Available at: https://bit.ly/3tXZhDl
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