•
• Although patients with SCD have benefited from past clinical trials, there are barriers to trial awareness and enrollment (e.g., mistrust of research studies, emotional issues, practical considerations)3
• RISE UP, a randomized, double-blind, placebo-controlled,multicenter phase 2/3 clinical trial of mitapivat, a pyruvate kinase activator under investigation for treatment of patients with SCD (NCT05031780)4, utilized an innovative, patient-forwardapproach to clinical trial design, awareness, and recruitment that considered patient preferences wherever possible
OBJECTIVE
• Using Agios' RISE UP Phase 2/3 trial, redefine best practices in clinical trial design by: 1. Asking patients with SCD to describe what matters most to them in a trial setting
2. Involving patients in decision making processes and trial awareness communications
METHODS
Protocol Design
• 9 patients with SCD (>16 years of age) and advocates (Bahrain n=1, France n=1, United Kingdom n=2, United States n=5) took part in a series of clinical trial design workshops
• 4 remote patient advisory board interviews were held with patients and advocates to consult on the RISE UP Phase 2/3 clinical trial design
• Patient perspectives were sought in the following areas:
- Meaningful trial parameters - Study duration
- Post-studyaccess to treatment - Study endpoints
- Eligibility criteria
- Assessments and procedures
- Operational support needs (e.g., visit frequency and locations) - Compensation considerations
- Pain reporting
• Insights gained from these consultations were incorporated into the proposed trial protocol design that was subsequently shared with Health Authorities (HAs) for their comment from a regulatory perspective
• Once finalized, key patient-relatedfeedback from HAs was presented to the patient advisory board to determine whether changes requested by HAs met the needs and barriers-to-uptakeexpressed during partner consultations
Awareness Campaign
• In addition, a group of 7 patients (5 US patients from the clinical trial design workshops and 2 additional US patient advocates) co-createdthe RISE UP phase 2/3 clinical trial awareness campaign, which sought to educate the community about the RISE UP clinical trial and value of patient participation
• It also sought to provide insights, build trust, and improve engagement of patients with SCD with respect to clinical trial awareness and enrollment in the RISE UP study
• A combination of communication approaches focused on:
Clinical trials remain essential for identifying new, safe, and effective therapies; however, patient involvement in clinical trial design is often late or absent2
BACKGROUND
• Sickle cell disease (SCD) is an inherited blood disorder characterized by mutations in the β-globinchain of hemoglobin, leading to red blood cell sickling, hemolytic anemia, pain events, and end-organdamage in cardiopulmonary, central nervous, and renal systems1
• SCD affects >3 million people worldwide and ~100,000 people in the United States1
• There are limited treatment options and a need remains for additional disease modifying therapies

A Patient-Centric Approach to Sickle Cell Disease Clinical Trials: Integrating Patient Perspectives in the RISE

UP Phase 2/3 Trial of Mitapivat for Informed Protocol Design and Associated Patient Community Benefit

2376

Charles Jonassaint, PhD1, Blaze Armon Eppinger2, Dominique Friend3, Golie Lorenzo Green4, Mia Robinson5, Teonna Woolford6, DeMitrious Wyant7, Janie Davis8, Abdulafeez Oluyadi8, PharmD, Ahmar U Zaidi, MD8, Holly John8, Wally R Smith, MD9

1University of Pittsburgh Medical Center, Pittsburgh, PA; 2Independent Contributor, Eatonton, GA; 3Independent Contributor, Orlando, FL; 4Independent Contributor, Houston, TX; 5Sickle Cell Awareness 365, Atlanta, GA; 6Sickle Cell Reproductive Health Education Directive, Owings Mills, MD; 7Independent Contributor, Washington, DC; 8Agios Pharmaceuticals, Cambridge, MA; 9Virginia Commonwealth University, Richmond, VA

  • The campaign launched a YouTube advertisement during World Sickle Cell Day 2022 (June 19) and monitored site traffic to the video, as well as to clinicaltrials.gov, Twitter, and the RISE UP clinical trial website
  • Media metrics, including views, clicks, and webpage visits, as well as other key performance indicators were used to measure campaign success as well as infer insights for future trial design or awareness campaigns

RESULTS

  • Patient contributions were considered at appropriate points throughout the drug development process (Figure 1)

Figure 1. Patient engagement process

Phase 2/3 Clinical Trial

Enrollment Campaign

Continued Development

Design

Drug Development

Journey

Tracking enrollment

Patients notified of trial

Patients notified of

regulatory feedback

uptake and online

milestones and consulted

and final trial

design

engagement

on next steps

Proposal made

Patients participation in

to regulators,

promotional materials

feedback

received

Patient recommendations

Patient selection of

incorporated in initial trial

campaign idea

design

Patient advisory

Patient opinions on trial

board formed for

messaging collected

collection of

perspectives

Protocol Design

  • Patient contributions to the protocol design included modified inclusion/exclusion criteria and the addition of pain (beyond pain crises) and fatigue as study outcomes; an overview is shown in Table 1
    • As per patient input, the trial was adjusted to include a recommendation for tailored management of SCD pain crises using a daily diary; the trial also approved reimbursement for study-related travel, lodging, and specific non- study assessments

Table 1. RISE UP trial design, summary of community feedback on different aspects of the study design

Study Aspects

Community Feedback

Protocol Design Elements

Study

•

12-month study duration may

•

Approximately monthly study visits

Duration

hamper participation and/or

for 7 months, followed by visits

compromise compliance

every 3 months

Post-study

•

Important to provide patients

•

An open label extension period

access

access to treatment after

was also added with visits on the

completion of the clinical trial

2nd, 4th, 8th, and 12th weeks of the

extension period, followed by

every 3 months up to 1.5 years

and every 6 months thereafter

Campaign

  • An example of a campaign that was co-created with the sickle cell warriors can be seen in Figure 2

Figure 2. Campaign co-created with sickle cell warriors

  • The RISE UP campaign heightened interest within the community for clinical trial participation (Figure 3)
    • Strong social media engagement and digital efforts resulted in increased trial website views
    • Community education and awareness efforts resulted in increased clinicaltrials.gov views to an average of 2-3 clicks per day

Figure 3. Media metrics following RISE Up campaign launch during

World Sickle Cell Day

Table 2. Key learnings and recommendations for patient involvement in trial design and recruitment

Action

Learnings

Recommendations

Trial design

• Prioritizing patient input

•

Create patient advisory board to guide

and involvement can

decision-making processes

enhance the clinical trial

•

Take action on recommendations and keep

design process and help

patients informed of continued

address patient concerns

developments

•

Ensure trial protocol meets both regulatory

requirements and patient needs

Patient relevant

• Including patient-

•

Prioritize the development of the most

endpoints

centered outcomes and

convenient protocol possible for patients

endpoints improves data

based on their lived experience

collection methods

Trial awareness

• Patient involvement can

• Build relationships and trust with patients,

create a uniquely

families, and patient advocacy groups

impactful and

• Engage local and national decisionmakers

differentiated awareness

and influencers

approach

•

Provide information to patients in a

comprehensive manner, tailored to

common questions and potential

concerns

Communications

• Meeting patients where

• Leverage social media platforms for

channels

they are, using familiar

campaign reach and engagement

language and engaging

• Allow patients to guide the process to

with their priorities drives

generate authenticity and trust among

engagement and action

peers

• Monitor traffic to trial websites and clinical trial registration platforms to assess impact and course correct, as needed

CONCLUSIONS

  • By partnering with patients with SCD to gather their contribution to protocol design, Agios integrated feedback from patients into the design and implementation of the study
  • The campaign succeeded in building awareness and engagement with patients, families, and advocacy groups, as well as local and national decision-makers and influencers
    • The Phase 2 portion of the RISE UP clinical trial was launched on time and fully enrolled, a notable result given that 80% of clinical trials globally are delayed due to missed enrollment targets5
  • Learnings and recommendations from this innovative patient-forward approach may be applied further throughout the drug development process
  • Reaching/engaging individuals and local community groups, fostering relationships, and building trust to gain support
  • Connecting with decision-makers and influential individuals who could advance the campaign's objectives

Study

•

Evaluate effect as assessed by

•

Key secondary and other

endpoints

high quality patient-reported

secondary endpoints in the study

outcomes (PROs)

include Health-Related Quality of

•

Evaluate pain and fatigue

Life and Performance Outcome

•

Provide flexibility with

Assessments

questionnaire and minimize

questionnaire burden

Eligibility

•

Assessing effect in patients with

•

Subgroup analyses specified in the

criteria

Hb <8 g/dL could be beneficial

protocol based on baseline Hb (<8

•

Prohibiting concomitant therapies

g/dL, >=8 g/dL)

(e.g., hydroxyurea or exchange

transfusion) may preclude patient

participation

Hb, hemoglobin; PRO, patient reported outcome.

Key Learnings and Recommendations for Future Patient Engagement

  • Patient engagement for clinical trial design for the RISE UP study yielded important insights relating to trial design, endpoint selection, trial awareness, and effective use of communication channels (Table 2)

By engaging with patient communities, the RISE UP campaign was able

to build trust, engage with local and national decisionmakers, and

provide timely information to patients, allowing them to make informed

decisions about trial participation

Disclosures

  • This study was funded by Agios Pharmaceuticals, Inc.
  • Writing support was provided by FleishmanHillard, funded by Agios Pharmaceuticals, Inc.
  • Abdulafeez Oluyadi, Ahmar U. Zaidi, Holly John, and Janie Davis are active employees at Agios Pharmaceuticals
  • Received honoraria from Agios: Blaze Eppinger, DeMitrious Wyant, Dominique Friend, Golie L. Green, Mia Robinson, and Teonna Woolford
  • Charles Jonassaint: Honoraria received from Agios; employed by and current shareholder in Expressive Painimation
  • Wally Smith: Honoraria received from: Agios, Novartis, bluebird bio, and Pfizer

Acknowledgments

  • Thank you to the Sickle Cell Warriors who participated and their families, our collaborators, the study investigators, and our advisors in the patient and clinical communities
  • We would like to acknowledge Agios Pharmaceuticals, Inc. for supporting and funding this campaign and study

References: 1. Brandow AM, Liem RI. J Hematol Oncol. 2022;15(1):20; 2. Geißler et al. Commun Med 2022;2,94; 3. Lebensburger JD et al. Pediatr Blood Cancer. 2013;60(8):1333-1337;4. ClincalTrials.gov. A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP). https://classic.clinicaltrials.gov/ct2/show/NCT05031780. Accessed Oct 27, 2023; 5. Desai M. Perspect Clin Res. 2020;11(2):51-53.

This study was funded by Agios Pharmaceuticals, Inc.​

Presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, December 9-12, 2023, San Diego, CA, USA, and Virtual​​

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Agios Pharmaceuticals Inc. published this content on 09 December 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 19 December 2023 18:03:30 UTC.