PREDICT Therapy Selection for JAK, T-cell, or IL-6 Inhibitor Therapies Using a Molecular Signature Response Classifier (PREDICT)
Conditions: Rheumatoid Arthritis
Sponsor: Scipher Medicine

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PREDICT Therapy Selection for JAK, T-cell, or IL-6 Inhibitor Therapies Using 
a Molecular Signature Response Classifier (PREDICT) 
Protocol Number: PREDICT-001 
Version: 1.0 
Date: 22-Feb-2024 
Sponsor: 
Scipher Medicine Corporation 
500 Totten Pond Road, Floor 6 
Waltham, MA 02451 
The information contained in this document is supplied as a background for clinical investigations. The 
document contains proprietary and confidential information that is the intellectual property of Scipher 
Medicine Corporation and shall not be disclosed in whole or in part or used for any purpose other than set 
forth in this protocol without the expressed written consent of Scipher Medicine Corporation. 

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Table of Contents 
1.
Key Personnel............................................................................................................................. 5 
2.
Protocol Signature Page ............................................................................................................. 6 
3.
Protocol Summary ...................................................................................................................... 7 
3.1. 
Synopsis.................................................................................................................................. 7 
3.2. 
Study Schema ......................................................................................................................... 9 
4.
Introduction ............................................................................................................................. 10 
4.1. 
Introduction .......................................................................................................................... 10 
4.2. 
Background .......................................................................................................................... 10 
4.3. 
Study Purpose ....................................................................................................................... 10 
4.4. 
Intended Use* ....................................................................................................................... 11 
5.
Study Endpoints ....................................................................................................................... 11 
5.1. 
Primary Endpoint .................................................................................................................. 11 
5.2. 
Secondary Endpoint .............................................................................................................. 11 
5.3. 
Exploratory Endpoints ........................................................................................................... 11 
6.
Study Design ............................................................................................................................ 11 
6.1. 
Study Type ............................................................................................................................ 11 
6.2. 
Study Population .................................................................................................................. 12 
6.3. 
Patient Selection Criteria....................................................................................................... 12 
6.3.1. 
Inclusion Criteria ............................................................................................................... 12 
6.3.2. 
Exclusion Criteria ............................................................................................................... 13 
7.
Study Procedures...................................................................................................................... 13 
7.1. 
Summary of Visits and Assessments ...................................................................................... 13 
7.2. 
Participant Identification, Recruitment, Pre-Screening ........................................................... 15 
7.3. 
Screening .............................................................................................................................. 15 
7.4. 
Informed Consent Process ..................................................................................................... 15 
7.5. 
Enrollment ............................................................................................................................ 15 
7.6. 
Schedule of Assessments ....................................................................................................... 16 
7.7. 
Research Specimen Collection ............................................................................................... 17 
7.8. 
Study Treatments ................................................................................................................. 17 
7.8.1. 
Therapy, Dose, Modes of Administration ........................................................................... 17 

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7.8.2. 
Stratification ..................................................................................................................... 17 
7.8.3. 
Duration of Study and Treatment Selection ........................................................................ 17 
7.8.4. 
Cost to Participants and Medication Expenses ................................................................... 18 
7.8.5. 
Concomitant Treatments ................................................................................................... 18 
7.8.6. 
Participant Reimbursement ............................................................................................... 18 
7.8.7. 
Patient Withdrawal/ Completion ....................................................................................... 18 
8.
Data Collected and Statistical Methods .................................................................................... 18 
8.1. 
Metadata Summary .............................................................................................................. 18 
8.2. 
Statistical Methods ............................................................................................................... 20 
8.2.1. 
Baseline Data .................................................................................................................... 20 
8.2.2. 
Analysis of Primary Outcome of Interest ............................................................................ 20 
8.2.3. 
Missing Data ..................................................................................................................... 20 
8.2.4. 
Sample Size ....................................................................................................................... 20 
9.
Data Handling and Record Keeping .......................................................................................... 20 
9.1. 
Study Database .................................................................................................................... 20 
9.2. 
Inspection of Records ............................................................................................................ 21 
9.3. 
Retention of Records ............................................................................................................. 21 
9.4. 
Optional Medical Record Retrieval, Linking to Electronic Health Records, and/or Tokenized 
Healthcare Data .............................................................................................................................. 21 
9.5. 
Confidentiality of Records ..................................................................................................... 21 
9.6. 
Review of Records ................................................................................................................. 22 
10.
Quality Control ..................................................................................................................... 22 
10.1. 
Data Quality ...................................................................................................................... 22 
10.2. 
Protocol Deviations ........................................................................................................... 22 
10.3. 
Publications....................................................................................................................... 22 
10.4. 
Future Use of Data or Specimens ....................................................................................... 23 
11.
Safety Assessments ............................................................................................................... 23 
11.1. 
Risk/Benefit Assessment and Anticipated and Unanticipated Adverse Device Effects .......... 23 
11.2. 
Alternatives to Participation .............................................................................................. 23 
12.
Regulatory, Ethical, and Study Oversight ............................................................................... 23 
12.1. 
Ethics Review .................................................................................................................... 24 

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12.2. 
Compliance and Ethical Conduct of the Study ..................................................................... 24 
12.3. 
Regulatory Status .............................................................................................................. 24 
12.4. 
Financial Disclosure ........................................................................................................... 24 
13.
Protocol Revision History ...................................................................................................... 25 
14.
References ............................................................................................................................ 25 
15.
Appendix .............................................................................................................................. 26 
15.1. 
List of Abbreviations and Key Terms .................................................................................. 26 
15.2. 
Definitions ......................................................................................................................... 27 
15.3. 
2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis ....................................... 28 
15.4. 
Informed Consent Form (ICF) ............................................................................................. 29 
The study staff and sponsor may want to contact you in the future. These are both optional. ....................... 34 
Do you give your permission for the investigator or staff to contact you regarding your willingness to 
participate in future research studies? ...................................................................................................... 34 
   Yes 
    No  Initials_________ ........................................................................................................... 34 
Do you give your permission for the study staff or sponsor to contact you to receive periodic email/ mail* 
with health-related articles, tips, and educational resources relevant to your disease? ................................. 34 
*All relevant material will comply with relevant data privacy regulations such as HIPAA. ........................... 34 
   Yes 
    No  Initials_________ ........................................................................................................... 34 
If yes to either or both, email, mailing address, and/or phone to be used for future contact ...................... 34 
Email: ________________________________________________________________ ................................. 34 
Mailing Address: ...................................................................................................................................... 34 
(Street)_______________________________________________________________ ................................. 34 
(City) _______________________(State) _______________ (Zipcode)____________ ................................. 34 
Phone Number: ________________________________________________________ ................................. 34 
   Yes 
    No  Initials_________ ........................................................................................................... 34 
15.5. 
CRF: Screening/ Baseline Visit (SBV) ................................................................................... 38 
15.6. 
CRF: Patient Reported Outcomes (PRO).............................................................................. 47 
15.7. 
CRF: Treatment Initiation Visit (TI) ..................................................................................... 52 
15.8. 
CRF: 24-week Follow-Up Visit............................................................................................. 54 
15.9. 
CRF: End of Study (EOS) ..................................................................................................... 59 
15.10. 
CRF: Unscheduled Visit: Change in Therapy (UVCT) ............................................................ 60 
15.11. 
CRF: Unscheduled Visit: Blood Re-Draw ............................................................................. 65 

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1. Key Personnel
Sponsor:
Jennifer Dines, MD 
Vice President, Regulatory and Medical Affairs 
Scipher Medicine Corporation  
500 Totten Pond Road, Floor 6 
Waltham, MA 02451    
April Cobb 
Senior Director, Clinical Operations 
Scipher Medicine Corporation  
500 Totten Pond Road, Floor 6 
Waltham, MA 02451    

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2. Protocol Signature Page
Protocol Title: PREDICT Therapy Selection for JAK, T-cell, or IL-6 Inhibitor Therapies Using a Molecular 
Signature Response Classifier (PREDICT) 
Protocol Number: PREDICT-001  
Protocol Version: 1.0 
Date: 02/22/2024 
Sponsor Name: Scipher Medicine Corporation 
Declaration of Principal Investigator 
I confirm that I have read the above-mentioned protocol and its attachments and understand it. I agree to conduct 
the described study in compliance with all stipulations of the protocol, as well as all applicable research 
regulations and ICH E6 Guideline for Good Clinical Practice (GCP). 
Principal Investigator Name: _______________________________________________ 
Principal Investigator Signature: ____________________________________________ 
Date: __________________________________________________________________ 

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3. Protocol Summary
3.1. Synopsis
Protocol Title 
PREDICT Therapy Selection for JAK, T-cell, or IL-6 Inhibitor Therapies Using a 
Molecular Signature Response Classifier (PREDICT) 
Study Description 
Prospective, multi-center-observational study conducted within the US, collecting 
patient samples for research and development to train, test, and validate precision 
medicine classifiers. These molecular signature response classifiers (MSRC) aim to 
predict response status to JAK, T-cell, and IL-6 inhibitor therapies in patients with 
rheumatoid arthritis (RA). 
Study Population 
RA patients with moderate or high disease activity and are eligible for treatment with 
a JAK, T-cell, or IL-6 inhibitor therapy who are either naïve to biologic and targeted 
synthetic DMARDs or TNFi-exposed. 
Study Objectives 
Collect patient blood samples, clinical, and laboratory data to develop, train, test, and 
validate precision medicine tests  
Inclusion Criteria 
1.
Patient is eighteen years of age, or older (≥18) at time of consent.
2.
Patient must meet the criteria for RA as defined by the 2010
ACR/EULAR classification at Visit 1 and documented by enrolling
PI.  
3.
Patient has active RA, with moderate or high disease activity as
confirmed by a CDAI score of >10 at Visit 1.
4.
Patients must have a history of failure, contraindication, or
intolerance to at least one csDMARD therapy.
5.
Patient must be b/tsDMARD-naïve or TNFi-exposed prior to
baseline visit only.
6.
Patient must be initiating one of the following listed therapies (including
biosimilars).
a.
JAK inhibitor therapy (only tofacitinib or upadacitinib)
b.
T-cell inhibitor therapy (abatacept)
c.
IL-6 inhibitor therapy (only tocilizumab)
7.
Concomitant treatments are permitted per standard of care and are not limited
to the following:
a.
csDMARD
i.
Methotrexate
ii.
Sulfasalazine
iii.
Leflunomide
iv.
Hydroxychloroquine
b.
Non-steroidal anti-inflammatory drugs
c.
Corticosteroids
8.
Patient may participate in another observational study.
9.
Patient is willing and able to complete the informed consent process and
comply with all study procedures and visit schedule.
Exclusion Criteria 
1.
Patient has previously participated in a Scipher Medicine study (NETWORK-
004, AIMs in RA, DRIVE, or INFORM).
2.
Patients who have been treated with an altMOA (non-TNFi therapy) therapy
for RA prior to baseline (Visit 1).
3.
Women who are known to be pregnant or breast-feeding or plan to get
pregnant during the study duration.
4.
Concurrent treatment with an investigational product or use of an
investigational product within 28 days of Visit 1.
5.
The use of RA therapies outside of an FDA approved indication.
6.
Patient is currently receiving systemic antimicrobial treatment for viral,
bacterial, fungal, or parasitic infection at the time of baseline visit (Visit 1).

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7.
Any known active, chronic, or recurrent invasive infection (e.g., listeriosis
and histoplasmosis) and viral infection that, based on the Investigator’s
clinical assessment, makes the patient an unsuitable candidate for the study.
This includes hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or
disseminated (even a single episode) herpes zoster, disseminated (even a
single episode) herpes simplex, or human immunodeficiency virus (HIV).
8.
Patient with any known active malignancy except non-melanoma skin cancer,
localized prostate cancer treated with curative intent with no evidence of
progression, low-risk or very low-risk (per standard guidelines) localized
prostate cancer under surveillance/watchful waiting (without intent to treat),
or carcinoma in situ of any type.
Study Duration 
24-weeks (+2 weeks or -4 weeks)
Study Endpoints 
Primary: Determine performance characteristics of the MSRC being developed, 
trained, and validated to predict a patient’s response status to specific biologic or 
targeted therapies (specifically targeting JAK, T-cell, and IL-6 inhibitors) among 
rheumatoid arthritis patients with moderate or high disease activity using standard 
clinical outcome measures (i.e. CDAI and/or ACR50) as determined by the analysis 
plan. 
Secondary: The discovery of novel genomic predictors of response status for specific 
JAK, T-cell, and IL-6 inhibitor therapies. 
Exploratory:  Including but not limited to  
-
Clinical outcome response rate of patients with a molecular signature
compared to the overall response rate of all patients given specific JAK, T-
cell, and IL-6 inhibitor therapies.
-
Clinical response rate to specific JAK, T-cell, and IL-6 inhibitor therapies
amongst patients with a molecular signature.
-
Adherence to assigned JAK, T-cell, and IL-6 inhibitor therapies.
-
Evaluation of patient reported outcomes (PROs) and response rate with a
molecular signature compared to overall response rate of all patients given
specific JAK, T-cell, and IL-6 inhibitor therapies.
Additional exploratory research and development may be performed and may include 
unrelated and additional analyses to these study endpoints, including but not limited 
to patient samples may be used for MSRC research & development prior to finalized 
locked MSRC validation study. 
Regulatory Status 
The MSRC is a minimal risk device and is exempt from 21 CFR 812.2(c) IDE 
regulation. The MSRC is a Laboratory Developed Test being researched, developed, 
and validated in this study is properly labeled in accordance with 21 CFR 809.10(c); 
is noninvasive and does not require an invasive sampling procedure; and is not used 
as a diagnostic procedure without confirmation of the diagnosis by another, medically 
established diagnostic product or procedure. 

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3.2. Study Schema 
FIGURE 1. PREDICT-001 Study Design 

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4. Introduction
4.1. Introduction 
Rheumatoid arthritis (RA) is a complex, chronic, systemic autoimmune disease that leads to inappropriate 
inflammation and systemic tissue damage leading to joint destruction, loss of function, and permanent irreversible 
disability (1). As RA progresses, it negatively affects the ability of patients to work and perform activities of daily 
living, leading to decreased quality and length of life (2,3). The objective of treatment is to slow, stop, or reverse 
disease progression and improve the quality of life for RA patients. 
Medication-based therapies comprise several classes of agents, including nonsteroidal anti-inflammatory drugs 
(NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biologic disease-
modifying antirheumatic drugs (bDMARDs). Biologic and non-biologic agents targeted at mediators of 
inflammation in RA are sometimes categorized collectively as targeted immune modulators (TIMs). TIMs 
represent a subcategory of DMARDs, including bDMARDs and targeted synthetic DMARDS (tsDMARDs), that 
have come into widespread use in the past decade. The clinical response to TIMs varies within phenotypically 
similar populations. Identifying those most likely to respond at a molecular level is an unmet need as earlier 
treatment with the right TIMs can slow disease progression (4,5). This study aims to develop, test, and validate 
precision medicine tests that identify which patients are more likely to respond to specific TIMs with a blood-
based MSRC.  
4.2. Background 
The 2021 American College of Rheumatology (ACR) Guideline for the Treatment of Rheumatoid Arthritis 
defines Treat-to-Target (T2T) as a treatment strategy in which the clinician treats the patient aggressively to reach 
and maintain T2T goals, such as low disease activity or remission, with regular assessment of disease progress 
and prompt switching of the medication regimen if targets are not achieved in a timely manner (6,7). The ACR 
also recommends using low disease activity (LDA) or remission as the target for a T2T approach for all RA 
patients (7). However, given the heterogeneity of underlying RA disease biology that manifests in a 
phenotypically similar patient population, it is challenging to determine which targeted treatment will be most 
effective for an individual patient who has failed csDMARDs. Due to this reason, clinical guidelines do not 
recommend any specific targeted therapies after csDMARD failure as all b/tsDMARDs share similar efficacies 
and safety profiles (7-9).  
These therapies span different biologic mechanisms of action (MOA) including tumor necrosis factor inhibitors 
(TNFi), IL-6, B-cell, T-cell, and JAK inhibitors (7,8). Patients with suboptimal responses often switch to 
alternative MOA through a trial-and-error process. There's a pressing need for a precision medicine test to help 
clinicians avoid prescribing ineffective therapies for RA. This approach would aim to achieve early, sustained low 
disease activity or remission by starting the patient on the right medicine sooner. 
The first molecular signature response classifier (MSRC), PrismRA®, was developed to predict inadequate 
response to TNFi therapies in both biologic-naïve and TNFi-exposed patients with RA (10-12), and the classifier 
is being expanded to include prediction of response status to other biologic or targeted therapies. This predictive 
test can lead to the selection of appropriate targeted therapy for RA patients based on their individual disease 
biology characteristics, as opposed to the conventional trial-and-error process.  
4.3. Study Purpose 
One of the forementioned challenges in treating RA is the substantial variability in clinical outcomes among 
patients stemming from the disease's diverse pathophysiology, which affects how patients respond to individual 
biological or targeted treatments. Notably, those who do not respond well to their first trialed biological therapy 
will likely find less success with subsequent biological or targeted synthetic DMARD (b/tsDMARD) treatments 
(13,14). Given this challenge, there is a pressing need for precision medicine tests that can predict a patient's 
response to specific therapies independent of prior treatment exposure. Such a tool would enable more 
personalized treatment approaches, helping patients achieve low disease activity or remission more rapidly. This 
approach is crucial, especially considering the "window of opportunity" in RA treatment, where early and 

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effective intervention can significantly alter the disease's course. Avoiding the traditional “fail forward” method 
would not only save time but also spare patients from unnecessary delays in receiving the most effective treatment 
for their specific case. 
Scipher Medicine Corporation is addressing this unmet need by developing a MSRC that accurately predicts, 
from a RA patient’s blood sample, the likelihood of achieving their treatment target on specific JAK, T-cell, and 
IL-6 inhibitor therapies. This study will collect patient blood samples, clinical, and laboratory results to develop, 
train, test, and validate precision medicine tests (MSRC). 
4.4. Intended Use* 
The MSRC is intended to be used by the treating clinician for patients with an established diagnosis of RA for 
whom current therapies (e.g., methotrexate) are not effectively managing symptoms, and who are considering 
starting a biologic or targeted therapy. The MSRC being developed, and validated aims to predict a patient’s 
likelihood of response or inadequate response to certain TNF, JAK, T-cell, and IL-6 inhibitor therapies so that 
resulting treatment selected is based on the patient’s unique disease biology. Consequently, a targeted therapy can 
be offered that has the best chance of success to treat moderate-to-severe RA. 
*Final MSRC developed and validated may have a different intended use and will be based on development done
prior to the validation of the precision medicine test.
5.
Study Endpoints
5.1. Primary Endpoint 
Determine performance characteristics of the MSRC being developed, trained, and validated to predict a patient’s 
response status to specific biologic or targeted therapies (specifically targeting JAK, T-cell, and IL-6 inhibitors) 
among rheumatoid arthritis patients with moderate or high disease activity using standard clinical outcome 
measures (i.e. CDAI and/or ACR50) as determined by the Clinical Validation Analysis Plan (CVAP) and 
associated Statistical Analysis Plan (SAP). 
5.2. Secondary Endpoint 
The discovery of novel genomic predictors of response status for specific JAK, T-cell, and IL-6 inhibitor 
therapies. 
5.3. Exploratory Endpoints 
Including but not limited to clinical outcome response rate of patients with a molecular signature compared to the 
overall response rate of all patients given specific JAK, T-cell, and IL-6 inhibitor therapies. 
Clinical response rate to specific JAK, T-cell, and IL-6 inhibitor therapies amongst patients with a molecular 
signature.  
Adherence to assigned JAK, T-cell, and IL-6 inhibitor therapies. 
Evaluation of patient reported outcomes (PROs) to determine response rate of patients with a molecular signature 
compared to overall response rate of all patients given specific JAK, T-cell, and IL-6 inhibitor therapies. 
Additional exploratory research and development may be performed and may include analyses unrelated to study 
endpoints; including but not limited to utilizing patient samples for R&D prior to finalized MSRC used in clinical 
validation.  
6.
Study Design
6.1. Study Type

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This is a prospective, multi-center-observational study conducted within the US, evaluating the clinical 
performance of a molecular signature response classifier (MSRC) to predict response status to specific JAK, T-
cell, and IL-6 inhibitor therapies in patients diagnosed with RA. 
Whole blood and serum will be collected at Visit 1, Visit 3, and if applicable, an Unscheduled Visit: Change in 
Therapy and/ or an Unscheduled Visit: Blood Re-Draw in two PAXgene® tubes and one serum separator tube 
(SST). Samples will be labeled and shipped to Scipher’s central laboratory for processing, testing, and generation 
of the molecular signature test results. Coded and de-identified data and/or specimens from the PAXgene® blood 
samples and/or SST may be used for future research or distributed to another third party for future use. CRP and 
anti-CCP values will be obtained by Scipher Medicine Laboratory for research purposes only and results will not 
be returned to the Investigator, patient nor enrolling sites. 
6.2. Study Population 
The study will enroll patients with a documented clinical diagnosis of RA with moderate-to-high disease activity 
(CDAI score >10) from the US across approximately 70 clinical and academic sites. Patients must have failed, 
had a contraindication, or intolerance to at least one non-biologic csDMARD therapy at the time of enrollment, 
are either b/tsDMARD-naïve or TNFi-exposed only, and are candidates for a specific JAK, T-cell, or IL-6 
inhibitor therapy, as described in this protocol. 
This study will screen approximately 1,500 patients across therapeutic modalities and at the discretion of the 
sponsor. Patients will be considered fully enrolled after they have initiated a biologic or targeted synthetic 
DMARD therapy during Visit 2 (index). The target for enrollment is approximately 1,100 patients. Final study 
enrollment numbers will be at the discretion of the sponsor and finalized in the CVAP and associated SAP. 
6.3. Patient Selection Criteria 
6.3.1. Inclusion Criteria 
1.
Patient is eighteen years of age, or older (≥18) at time of consent.
2.
Patient must meet the criteria for RA as defined by the 2010 ACR/EULAR classification at Visit
1 and documented by enrolling PI.
3.
Patient has active RA, with moderate or high disease activity as confirmed by a CDAI score of
>10 at Visit 1.
4.
Patients must have a history of failure, contraindication, or intolerance to at least one csDMARD
therapy.
5.
Patient must be b/tsDMARD-naïve or TNFi-exposed prior to baseline visit only.
6.
Patient must be initiating one of the following listed therapies (including biosimilars):
a.
JAK inhibitor therapy (only tofacitnib or  upadacitinib)
b.
T-cell inhibitor therapy (abatacept)
c.
IL-6 inhibitor therapy (only tocilizumab)
7.
Concomitant treatments are permitted per standard of care and are not limited to the following:
a.
csDMARD
i.
Methotrexate
ii.
Sulfasalazine
iii.
Leflunomide
iv.
Hydroxychloroquine
b.
Non-steroidal anti-inflammatory drugs
c.
Corticosteroids
8.
Patient may participate in another observational study.
9.
Patient is willing and able to complete the informed consent process, comply with all study
procedures, and visit schedule.

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6.3.2. Exclusion Criteria 
1.
Patient has previously participated in a Scipher Medicine study (NETWORK-004, AIMs in RA, DRIVE,
or INFORM).
2.
Patients who have been treated with an altMOA (non-TNFi therapy) therapy for RA prior to
baseline (Visit 1).
3.
Women who are known to be pregnant or breast-feeding or plan to get pregnant during the study
duration.
4.
Concurrent treatment with an investigational product or use of an investigational product within
28 days prior to Visit 1.
5.
The use of RA therapies outside of the FDA approved indication.
6.
Patient is currently receiving systemic antimicrobial treatment for viral, bacterial, fungal, or
parasitic infection at the time of baseline visit (Visit 1).
7.
Any known active, chronic, or recurrent invasive infection (e.g., listeriosis and histoplasmosis)
and viral infection that, based on the Investigator’s clinical assessment, makes the patient an
unsuitable candidate for the study. This includes hepatitis B virus (HBV) or hepatitis C virus
(HCV), recurrent or disseminated (even a single episode) herpes zoster, disseminated (even a
single episode) herpes simplex, or human immunodeficiency virus (HIV).
8.
Patient with any known active malignancy except non-melanoma skin cancer, localized prostate
cancer treated with curative intent with no evidence of progression, low-risk or very low-risk
(per standard guidelines) localized prostate cancer under surveillance/watchful waiting (without
intent to treat), or carcinoma in situ of any type.
7.
Study Procedures
7.1. Summary of Visits and Assessments
•
Visit 1: Screening/Baseline
o
Time: +1 week*
o
Forms:
•
Informed Consent Form (ICF)
•
Screening/Baseline Visit (SBV)
•
Patient Reported Outcomes (PRO)
o
SBV Investigator Assessments: Medical history, comorbidities, demographics, physician global
assessment of disease activity, 28- tender and swollen joint count, and concomitant medications
o
PRO Assessments: Patient global assessment of pain and disease activity, RAPID3, and
Health Assessment Questionnaires (HAQ)
o
Standard Lab Tests: RF**
o
Obtain patient samples for research-only testing: Blood collection for PAXgene® tubes
(2), serum separator tube (1); anti-CCP and CRP***
•
Visit 2: Treatment Initiation****
o
Time: Within 8 weeks post Visit 1
o
Form: Treatment Initiation Visit
o
Investigator Assessments: Initiation of biologic or targeted therapy, changes to medical
history, comorbidities and concomitant medications
•
Visit 3: 24-week Follow-up*****
o
Time: 24-weeks post treatment initiation (+2 weeks or -4 weeks)
o
Forms:
•
Follow Up Visit (FUV)
•
Patient Reported Outcomes (PRO)
•
End of Study (EOS)
o
FUV Investigator Assessments: Changes to medical history, comorbidities, and

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concomitant medications, physician global assessment of disease activity, 28- tender 
and swollen joint count, and RA treatment adherence 
o
PRO Assessments: Patient global assessment of pain and disease activity, RAPID3, and Health
Assessment Questionnaires (HAQ)
o
Obtain patient samples for research-only testing: Blood collection for PAXgene® tubes
(2), serum separator tube (1); anti-CCP and CRP***
•
Unscheduled Visit: Blood Re-Draw*
o
Time: Within 2 weeks of scheduled blood-draw
o
Forms:
•
Unscheduled Visit Blood Re-Draw (UVBD)
o
UVBD Investigator Assessment: Changes to medical history, comorbidities and
concomitant medications 
o
PRO Assessments: None
o
Obtain patient samples for research-only testing: Blood collection for PAXgene® tubes
(2), serum separator tube (1); anti-CCP and CRP***
•
Unscheduled Visit: Change in Therapy*****
o
Time: N/A [Visit to be completed when a participant changes class of b/tsDMARD
therapy initiated at Visit 2]
o
Forms:
•
Unscheduled Visit Change in Therapy (UVCT)
•
Patient Reported Outcomes (PRO)
•
End of Study (EOS)
o
UVCT Investigator Assessments: Changes to medical history, comorbidities, and
concomitant medications, physician global assessment of disease activity, 28- tender
and swollen joint count, and RA treatment adherence
o
PRO Assessments: Patient global assessment of pain and disease activity, RAPID3,
Health Assessment Questionnaires (HAQ)
o
Obtain patient samples for research-only testing: Blood collection for PAXgene® tubes
(2), serum separator tube (1); anti-CCP and CRP***
*Clinical data and blood samples can be collected within 1 week of the initial screening/baseline visit. If the
original MSRC blood sample fails at Visit 1, Visit 3, or Unscheduled Visit: Change in Therapy and a recollection
is required, up to 2 weeks is allowed to complete an Unscheduled Visit: Blood Re-Draw.
**RF testing not necessary if previous results available via subject’s medical record and are within 1 year of Visit
1.
*** Anti-CCP and CRP values will be obtained by Scipher Medicine Laboratory for research purposes only and
will not be returned to the Investigator, patient nor enrolling sites. Patient samples must be shipped within 24
hours of the blood draw, but ideally the same day or next morning to avoid test failure. No samples should be
shipped on Saturday.
****If according to standard of care at treatment center, sites will be permitted to conduct Visit 2 over the phone
or virtual setting. Visit 2 may be conducted following Scipher Medicine Laboratory receiving and processing the
subject’s whole blood and serum collected at Visit 1, within 5 business days.
*****In-class therapy switch or adjustments to dose, route of administration, or frequency of b/tsDMARD
therapy initiated at Visit 2 will be permitted and rationale for change will be recorded. If a therapy from a
different class of b/tsDMARDs is initiated from Visit 2, the therapy, dose, route of administration, frequency and
rationale for changing therapy will be collected and a major protocol deviation will be recorded. In addition, the
patient will complete their Unscheduled Visit: Change in Therapy at that time.
The date of study treatment initiation (Visit 2) constitutes the index date for the beginning of the follow-up. The 
0-8 weeks period following Visit 1 will be used to ascertain all baseline data is collected and the patient has
initiated a treatment within this time frame. The 24-week follow-up (Visit 3) will be defined as the visit window
at 24 weeks (+2 weeks or -4 weeks) from the index date.

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Depending on final enrolled sample numbers and biostatistical power calculations and feasibility analyses, a data 
review may be conducted that may outline different follow-up (Visit 3) windows such as 24 (+6) weeks and 24 
(+8) weeks. In these instances, a minor protocol deviation will be recorded for patients whose Visit 3 assessments 
were collected outside 24-week (+2 weeks or -4 weeks) window, and they may be included in the final analyses.     
7.2. Participant Identification, Recruitment, Pre-Screening  
Before Visit 1 (Pre-Screening), patient charts may be reviewed to determine eligibility for the study. Participants 
will be identified and recruited by, but not limited to, clinicians and other health care personnel at participating 
sites, online and printed marketing material, and radio and television advertisements. The identification and 
recruitment of participants will protect privacy and be free of undue influence. All patient-facing material will be 
submitted to the IRB for approval prior to use.   
7.3. Screening 
At Visit 1, potential study participants will be screened by study team members according to inclusion and 
exclusion criteria as outlined in the “Section 6.3 Patient Selection Criteria” above, and informed consent will be 
obtained. 
7.4. Informed Consent Process 
At Visit 1, a written informed consent form (ICF) will be used to document consent of the patient. This must be 
obtained prior to recording of any tests or assessments under this protocol.   
The IRB approved informed consent form (ICF) will adhere to ICH GCP guidelines and comply with the United 
States Code of Federal Regulations as detailed in 21 CFR §50.25 and the Declaration of Helsinki. 
7.5. Enrollment 
1.
At Visit 1, patients will complete the informed consent form (ICF) process prior to any study specific
assessments being conducted. Each patient will be assigned a unique study identification number that will be
used to track their de-identified data throughout their participation in the study.
2.
At Visit 1, patient name, birth month and year and study identification number will be stored on a secure and
HIPAA-compliant research database. The sponsor will have  access to these data as applicable to appropriately
conduct the study and adhere to consent and opt-in consent at time of enrollment.
3.
At Visit 2, after the patient initiates one of the following targeted therapy options listed below, the patient will
be considered enrolled into the study:
•
JAK inhibitor therapy (only tofacitinib or upadacitinib)
•
T-cell inhibitor therapy (abatacept)
•
IL-6 inhibitor therapy (only tocilizumab)

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7.6. Schedule of Assessments 
1Changes to medical history and concomitant medications will be collected at all visits in the case report form 
(CRF). Information collected will include any changes to medication list and medical history collected at Visit 1. 
2Test result can be pulled from patient record if test results are within 1 year of Visit 1. If test result is not 
available, a new test is to be ordered using standard local lab ordering practices. 
3Anti-CCP and CRP values will be obtained by Scipher Medicine Laboratory for research purposes only and will 
not be returned to the Investigator, patient nor enrolling sites. 
4Only 3 questions (Questions I and J, and PtGA) from the RAPID3 assessment will be collected on the patient 
assessment form and the score will be computed based on these answers and related questions from HAQ by 
sponsor.  
5b/tsDMARD therapy the patient is on at time of Visit 1, if applicable, will be collected; Visit 2 will collect new 
Procedure 
Visit 1 
(Screening/ 
Baseline) 
Visit 2 
(Treatment 
Initiation) 
Visit 3 
(24-Week 
Follow-up)7 
Unscheduled Visit: 
Blood Re-Draw 
Unscheduled Visit: 
Change in Therapy 
Visit windows 
+1 week6
Within 8 weeks of 
Screening/Baseline 
+2 weeks or
-4 weeks
Within 2 weeks of 
scheduled blood-draw 
N/A 
Informed 
consent 
X 
Eligibility 
criteria 
X 
Medical history1 
X 
X 
X 
X 
X 
Prior medication 
history for RA 
X 
28-Joint count
for tenderness
X 
X 
X 
28-Joint count
for swelling
X 
X 
X 
Comorbidities 
X 
X 
X 
Smoking status 
X 
X 
X 
X 
X 
Height 
X 
X 
X 
Weight 
X 
X 
X 
RF2 
X 
Anti-CCP3 
X 
X 
X 
X 
2x PAXgene®
tubes 
X 
X 
X 
X 
1x Serum 
Separator tube 
X 
X 
X 
X 
CRP3 
X 
X 
X 
X 
Physician global 
assessment of 
disease activity 
X 
X 
X 
Patient global 
assessment of 
pain and disease 
activity 
X 
X 
X 
RAPID3 
assessment4 
X 
X 
X 
Health 
Assessment 
Questionnaire 
X 
X 
X 
Initiation of 
biologic or 
targeted therapy5 
X 
Rx Adherence 
Check 
X 
X 
b/tsDMARD 
therapy5 
X 
X 
X 
Concomitant 
medications1 
X 
X 
X 
X 
X 

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b/tsDMARD initiated; Between Visit 2 (index date) and Visit 3, in-class therapy switch or adjustments to dose, 
route of administration, or frequency of b/tsDMARD therapy initiated at Visit 2 will be permitted and rationale 
for change will be recorded. If a therapy from a different class of b/tsDMARDs is initiated following Visit 2, the 
therapy, dose, route of administration, frequency, and rationale for changing therapy will be collected and a major 
protocol deviation will be recorded. The patient will complete their Unscheduled Visit: Change in Therapy at that 
time. 
6Clinical data and blood samples can be collected within 1 week of the initial screening/baseline visit. If the 
original MSRC blood sample fails at Visit 1, Visit 3, or Unscheduled Visit: Change in Therapy and a recollection 
is required, up to 2 weeks allotted to complete Unscheduled Visit: Blood Re-Draw.  
7If there are no therapy class changes to the b/tsDMARD therapy initiated at Visit 2, patient will complete Visit 3 
after 24-weeks (+2 weeks or -4 weeks) of Visit 2, index date.  
7.7. Research Specimen Collection 
Whole blood and serum will be collected at Visit 1, Visit 3, and if applicable, Unscheduled Visit: Change in 
Therapy or Unscheduled Visit: Blood Re-Draw. Blood will be collected in two 2.5 mL PAXgene® tubes and one 
8-10 mL serum separator tube for a total 12 mL blood collection at Visit 1, Visit 3, and if applicable, Unscheduled
Visit: Change in Therapy or Unscheduled Visit: Blood Re-Draw. Blood will be processed according to
appropriate standard lab procedures.
Anticipated volume of blood to be drawn per patient over the scheduled study visits should not exceed 48 mL, 
unless standard of care tests are required. If the initial (Visit 1), follow-up (Visit 3), and/ or, if applicable, 
Unscheduled Visit: Change in Therapy MSRC analysis fails, a patient may have an Unscheduled Visit: Blood Re-
Draw performed for an additional blood draw for the MSRC analysis. 
Additional tests may be run on the participant’s samples. This will be explicitly stated in the consent form. 
7.8. Study Treatments 
Patients are to initiate their targeted therapy per clinical guidance of the Investigator at Visit 2, index date. Patients 
can be b/tsDMARD-naïve or TNFi-exposed only at Visit 1, prior to enrollment. 
7.8.1. Therapy, Dose, Modes of Administration 
Dosage and selection of biologic or targeted therapy is at the Investigator’s discretion, if within the FDA 
approved label.  
Before Visit 3, in-class therapy switch or adjustments to dose, route of administration, or frequency of 
b/tsDMARD therapy initiated at Visit 2 will be permitted and rationale for change will be recorded. If a therapy 
from a different class of b/tsDMARDs is initiated from Visit 2, the therapy, dose, route of administration, 
frequency and rationale for changing therapy will be collected and a major protocol deviation will be recorded. 
The patient will complete their Unscheduled Visit: Change in Therapy at that time.  
Information, including therapy, dose, route of administration, frequency, rational for change, and changes in 
medical history will be recorded for any change in b/tsDMARD therapy initiated at Visit 2 (index) in the study 
electronic data capture (EDC) system. 
7.8.2. Stratification 
Patients will be stratified based on the four potential biologic or targeted therapies in an approximate ratio of 
225:225:225:225 for tofacitnib (JAKi): upadacitinib (JAKi): tocilizumab (IL-6i): and abatacept (T-cell inhibitor). 
These ratios are subject to change and at the discretion of study sponsor. Final cohort numbers will be outlined in 
the CVAP and associated SAP. If during the study, certain therapy arms are fully enrolled, the study sponsor may 
limit additional patients from enrolling and participating in the study within fully enrolled therapy arms.  
7.8.3. Duration of Study and Treatment Selection 

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The study is 24 weeks (+2 weeks or - 4 weeks) in duration and is indexed after the patient’s therapy is initiated at 
Visit 2 (index date) and associated clinical and laboratory data are collected. 
7.8.4. Cost to Participants and Medication Expenses  
This study is an observational study, and the Sponsor will not cover any medication costs or standard of care labs 
associated with this study. The Sponsor will pay for research procedures associated with the study and necessary 
for follow-up. Participants will not incur any costs, nor will insurance be billed for research procedures in this 
study which include venipuncture and medical record retrieval if applicable. Participants will not be compensated 
for any missed visits.  
7.8.5. Concomitant Treatments 
If the Investigator deems it medically necessary, a patient’s concomitant treatment can be adjusted after Visit 1 
and before Visit 3. Any changes to the dose, route of administration, frequency, and rational for change of 
concomitant medications during the course of the study will be collected at all study visits including Visit 2 
(index), Visit 3 (24-week follow-up), and if applicable, Unscheduled Visit: Blood Re-Draw and/or Unscheduled 
Visit: Change in Therapy. 
7.8.6. Participant Reimbursement 
Patients will be reimbursed for their time participating in the study. Participants will qualify for visit 
compensation after the completion of the corresponding visit and all visit-related procedures. Participants will be 
compensated the following amounts for each respective visit completed: $100 for Visit 1, $50 for Visit 2, $100 
for Visit 3 or an Unscheduled Visit: Change in Therapy, and $50 for an Unscheduled Visit: Blood Re-Draw.  
7.8.7. Patient Withdrawal/ Completion  
Patients may withdraw from the study at any time without prejudice to their care. The Investigator and/or the 
Sponsor or designee may withdraw patients at any time who violate the study protocol, to protect the patient for 
safety reasons, for administrative or other reasons at any time. It will be documented whether each patient 
completes the determined follow-up visits or not and rationale for withdrawal. 
8. Data Collected and Statistical Methods
8.1. Metadata Summary 
The following data will be collected from the study-eligible patients at Visit 1. 
Domain 
Variables 
Demographics 
•
Age (calculated from birth month and year)
•
Sex at birth
•
Race (American Indian or Alaskan Native, Asian, Black or African
American, Native Hawaiian or Other Pacific Islander, White,
Other, Unknown)
•
Ethnicity (Hispanic, Non-Hispanic, Not reported, Unknown)
•
Geography (zip code and state of residence)
•
Height, Weight, BMI
Lifestyle 
•
Smoking (current, former, or never smoker)
RA related 
•
Date of RA diagnosis
•
Seropositivity (seropositive or seronegative)
o
RF status (positive or negative)
o
Anti-CCP status (positive or negative)
•
CRP
•
CDAI at baseline

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•
Previous use of TNFi therapy
•
TJC and SJC at baseline
•
PGA at baseline
•
PtGA at baseline
•
RAPID3 at baseline
•
HAQ at baseline
Concurrent RA medication dosage, route, frequency, and duration 
•
csDMARDs
•
Folic Acid
•
NSAIDs
•
Glucocorticoids
Comorbidities 
(Medical 
History) 
•
Cardiovascular disease (including but not limited to Myocardial
infarction, Cerebral Vascular Accident (CVA), Transient Ischemic
Attack (TIA), Congestive Heart Failure (CHF))
•
Hypertension
•
Anemia or other blood disease
•
Lung disease
•
Diabetes
•
Ulcer or stomach disease
•
Kidney disease
•
Liver disease
•
Cancer
•
Osteoarthritis, degenerative arthritis
•
Back Pain
•
Fractures spine, hip, or leg
•
Depression
Patient data will be collected from clinical assessments, medical records, laboratory results, and surveys at 
screening/ baseline (Visit 1), treatment initiation (Visit 2), 24-week follow-up visit (Visit 3), Unscheduled Visit: 
Blood Re-Draw, and Unscheduled Visit: Change in Therapy and entered in the study EDC.  
If a completed medical records release form is on file, comprehensive demographic, medical, and health 
information (if available) may be directly collected from the patient’s electronic medical records by the study sites 
or sponsor. Electronic Medical Records (EMR) data may be obtained indefinitely following a patient’s enrolment 
unless the patient withdraws authorization.  
CRP and anti-CCP data from the Visit 1, Visit 3, Unscheduled Visit: Blood Re-Draw, and Unscheduled Visit: 
Change in Therapy samples will be stored at Scipher Medicine’s Clinical Laboratory Improvement Amendments 
(CLIA)-certified and College of American Pathologists (CAP)-accredited laboratory.  
In order to reduce the loss of patients to follow-up, all patients will be asked for their personal contact information 
and an alternate person’s contact information. Patients may be directly contacted by the Investigator or 
Sponsor/designee in order to support study follow-up. The designated alternate contact person may also be 
directly contacted in the event the patient cannot be reached.  
For patients who are lost to follow-up, Investigator or Sponsor/designee will search available health status 
databases to determine vital status and cause of death in the case of mortality.  

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8.2. Statistical Methods 
Additional information regarding the statistical methods and plan will supersede the following section (if 
applicable) and will be documented in the SAP for the Clinical Validation of MSRC. Samples to validate the 
classifier will be utilized from this study as well as retrospective samples collected in prior studies. This will be 
outlined in the CVAP and associated SAP.  
8.2.1. Baseline Data 
The primary and demographic variables will be examined with summary statistics, including means, medians, 
standard deviations (SD), minimum, and maximum values for continuous variables, and frequencies and 
proportions for categorical variables. 
8.2.2. Analysis of Primary Outcome of Interest 
MSRC performance characteristics will be determined by analyzing the samples collected in this study, with 
consideration of samples collected from other studies, and comparing the predicted response labels to the true 
clinical classifications.   
8.2.3. Missing Data  
Missing data will be minimized through rigorous conduct of data collection and monitoring as described in 
Section 8.1. No statistical methods will be employed to address missing data. 
8.2.4. Sample Size 
Approximately 1,500 participants will be enrolled in this study. Samples are to be collected prospectively for this 
study, with at least 300 patients enrolled the study for each standard of care therapy. The power analysis and 
sample size calculation details will be outlined in the CVAP and associated SAP. 
9. Data Handling and Record Keeping
9.1. Study Database 
Data will be collected in the study database through a secure, electronic database capture (EDC) system or an 
electronic data transfer via an encrypted secure sockets layer protocol as applicable. 
Electronic case report forms will be maintained in the EDC, and all relevant observations and data related to the 
protocol-defined assessments will be recorded. This will include, at minimum, medical history, laboratory results, 
sample collection records, treatment information, and patient reported assessments. 
Participants birth month and year will be recorded to determine satisfaction of inclusion criterion (age ≥18 at time 
of first study activity). 
Prior to recording data in the eCRF, Investigators and site staff will be trained on how to use the EDC system. 
Investigators or the assigned trained and qualified site staff are responsible for ensuring timely and accurate data 
entry into the EDC system within 5 business days. Records of the patient visits will be filed as source documents 
for this study and used to input the data into the study database. If applicable, site specific assigned trained and 
qualified Sponsor or Sponsor designee may record timely and accurate data entry into the EDC system within 5 
business days.   
Investigators or assigned Sponsor or Sponsor designees are responsible for overseeing the eCRFs, including 
resolving data queries, reviewing and approving all changes to the patient data, and providing final approval of 
the data. The Investigator will provide final approval by electronically signing and dating each eCRF. Signed 
eCRFs will be retained in secure archives. 
The study database will be password protected and access provided only to trained and authorized personnel. Data 

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collected into the study database may include protected health information (PHI). This PHI will not be shared 
beyond the Sponsor/designee or regulatory bodies as warranted and allowed based on patient’s consent and 
optional opt-ins. 
9.2. Inspection of Records 
Sponsor or its designee will be allowed to conduct site visits either remotely or at the Investigator’s clinical 
research facilities for the purpose of monitoring any aspect of the study. The Investigator agrees to allow the 
Sponsor or its designee to inspect the facilities, patient medical records, source documents, and any other records 
relevant to conduct the study. Data containing patient health information will be maintained in a confidential 
manner. If necessary, source documents containing PHI will be protected and may be transferred to the Sponsor 
or Sponsor designee via a secure, HIPAA compliant portal. Data containing patient health information will be 
maintained in a confidential manner. 
9.3. Retention of Records 
All primary data that are a result of the original observations and activities of the study and that are necessary for 
the reconstruction and evaluation of any study report will be retained in a secure archive at the study site for a 
period not less than 6 years after the last approval of a marketing application in an International Council for 
Harmonization (ICH) region, and until there are no pending or contemplated marketing applications in an ICH 
region, or until at least 6 years have lapsed since the formal discontinuation of the clinical development of the 
MSRC. All relevant country and region-specific requirements that may be more stringent than the 6 years 
included in ICH shall be followed. 
The site will maintain an Investigator Site File (ISF), which will be maintained at the study site and in accordance 
with local and Federal regulations, as applicable. The site must keep this ISF current and available for review by 
the Sponsor, IRB, and/or regulatory bodies. 
9.4. Optional Medical Record Retrieval, Linking to Electronic Health Records, and/or Tokenized 
Healthcare Data 
As part of this study, protected health information, with the participant's consent, will be accessed to confirm 
medical information pertaining to the participant's medical history, symptoms, and diagnostic tests 
performed for rheumatoid arthritis and relevant comorbidities to collect all required study-related data.  
Participants have the option to also authorize via a HIPAA-compliant authorization (“HIPAA form”) additional 
access to medical records and claims data related to their rheumatoid arthritis condition or other autoimmune or 
immune-mediated conditions. The HIPAA form will authorize participants’ physicians to give study personnel, 
including the study sponsor access to the participants’ electronic health records and medical claims data. This may 
include but is not limited to authorizing the identifiable pairing of tokenized healthcare data with study data and 
residual blood samples on an ongoing basis. This will be explicitly stated in study consent form.  
9.5. Confidentiality of Records 
All study sites, laboratories, and parties supporting this study must comply with HIPAA, where applicable. All 
data and records generated throughout this study will be kept confidential in accordance with local and Federal 
policies. 
At consent, personal identifying information, including subject name, zip code, birth month and year, and contact 
information will be collected and stored on a secure and HIPAA-compliant research database. 
Following consent, each subject will be assigned a unique study identification number that will be used to track 
their de-identified data. Sample tubes collected and sent to Sponsor or delegates may include PHI. Upon receipt of 
samples, the unique study identification number will replace PHI during processing and prior to storage. 

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Records that may have patient identifying information will be kept confidential in accordance with applicable 
guidelines, regulations, and laws, as described in Section 12.2. 
9.6. Review of Records 
Sponsor and/or its designee will review source documents (i.e., medical records, laboratory results) and data 
collected throughout the study as applicable. In addition, an auditor, IRB, FDA, or national or local regulatory 
authorities may access and review applicable source documents, records, and data. All patients will be notified 
and provide consent to this possibility, during the consenting process. 
10.
Quality Control
10.1. Data Quality  
Site and data monitoring will occur in accordance with the clinical monitoring plan. Data captured in the study 
database will be compared against the source data for completeness and accuracy. Discrepancies will be addressed 
and corrected, if required, by qualified site personnel and sponsor as applicable. 
eCRF data will also be routinely reviewed for timeliness, errors, accuracy, and omissions. Data queries will be 
created and submitted to the sites for data requiring further clarification. Qualified site personnel will address 
queries and correct data in the study database. 
10.2. Protocol Deviations 
Study sites and database will be evaluated for protocol deviations which include but are not limited to: 
•
Minor protocol deviations:
o
Depending on final enrolled sample numbers and biostatistical power calculations and feasibility
analyses, a data review may be conducted that may outline different follow-up (Visit 3) windows
such as 24 (+6) weeks and 24 (+8) weeks. In these instances, a minor protocol deviation will be
recorded for patients whose Visit 3 assessments were collected outside 24-week (+2 weeks or -4
weeks) window, and they may be included in the final analyses.
•
Major protocol deviations:
o
If a therapy from a different class of b/tsDMARD is initiated after Visit 2’s therapy, the new
therapy, dose, route of administration, frequency and rationale for changing therapy will be
collected and a major protocol deviation will be recorded. The patient will complete their
Unscheduled Visit: Change in Therapy at that time.
o
If study assessments and procedures are conducted prior to obtaining a signed ICF, a major
protocol deviation will be recorded, the patient will be excluded from completing the study, and
the End of Study (EOS) form will be completed.
o
If a participant entered the study or initiated treatment at Visit 2 but did not satisfy the inclusion
and exclusion criteria outlined in Section 6.3, a major protocol deviation will be recorded, the
patient will be excluded from completing the study, and the End of Study (EOS) form will be
completed.
A quarterly deviation meeting will be held by Sponsor to evaluate deviations identified during the study. Data 
integrity mitigation will be completed to ensure statistical power is not jeopardized and/or need for protocol 
amendments as applicable. The number and type of protocol deviations will be analyzed by the Sponsor to review 
the events by site to determine if the deviations could affect the integrity of the study data. The study 
biostatistician will report findings to the Sponsor. Sites with multiple deviations may be required to have 
remediation training as applicable. 
10.3. Publications 
If any results of the study are presented at scientific conferences or published, the subject’s identity will remain 
confidential. 

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10.4. Future Use of Data or Specimens 
De-identified data and samples collected and processed throughout the study may be used for future research 
and/or distributed to other investigators or third parties for future efforts at the discretion of the Sponsor. This 
includes but is not limited to Research & Development (R&D), Verification and Validation (V&V), or other 
commercial purposes.  
MSRC samples processed at Scipher Medicine’s CAP-accredited and CLIA-certified laboratory from study 
participants will also be de-identified and used for future research and/or distributed to partners, other third parties 
or investigators. Future research and other efforts include but is not limited to extracting and sequencing 
DNA/RNA or other analytical methodologies on the blood and serum samples. Future efforts may also include 
discovering novel biomarkers for disease diagnosis, monitoring, or progression as well as discovering new disease 
mechanisms, therapeutic targets, and therapies for autoimmune disorders. 
De-identified data and specimen samples may be stored indefinitely or until the sample is exhausted following 
study completion. The de-identified data and specimens may be shared with research/institutions, third parties 
outside of Sponsor without additional informed consent from the participant or the legally authorized 
representative. This could include for-profit companies. 
Participants may withdraw from the study at any time. Following a written request, if applicable, efforts will be 
made to remove their data and specimens. 
11. Safety Assessments
11.1. Risk/Benefit Assessment and Anticipated and Unanticipated Adverse Device Effects 
This is a minimal risk study and potential risks include standard risks associated with a venipuncture procedure, 
including: 
Faintness, inflammation of the vein, bruising, temporary discomfort, and bleeding at the site of puncture. Though 
rare, infection may also occur. No unanticipated adverse device effects (UADE) will be reported for this study.  
The blood draw and MSRC test is not expected to result in either anticipated or unanticipated adverse device 
effects (UADE) as it involves the analysis of ex-vivo blood samples from the participants and results will not be 
returned to the Investigator, patient nor enrolling sites during the study. The final MSRC being developed, 
trained, and validated will be determined by Scipher. In addition, all test results obtained for research-purposes 
only, including anti-CCP and CRP, will not be returned to Investigator, patients nor enrolling sites and will be 
conducted by the Scipher laboratory which is certified under the Clinical Laboratory Improvement Amendments 
(CLIA) and is College of American Pathologists (CAP)-accredited. 
There are no investigational therapies being evaluated per the protocol. Patients will be treated for their RA in 
accordance with the standard of care by their treating physician. The Investigator is expected to follow all aspects 
of the FDA prescribing information when administering a pharmaceutical product in the course of treatment of 
patients included in this study. 
Additional risks include a potential for loss of confidentiality by participating in this study. 
No direct benefits from the study will be experienced by the patient.  
11.2. Alternatives to Participation 
Options include not participating or participating in other observational research studies. Not participating in this 
study will have no impact on the clinical care provided by clinician. 
12. Regulatory, Ethical, and Study Oversight

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12.1. Ethics Review 
The protocol, ICF, and any advertisements must be approved or given a favorable opinion in writing by an IRB. 
The Investigator must submit written and dated verification of the IRB approval to Sponsor or designee before he 
or she can enroll any patients into the study. 
The Sponsor/designee or Investigator will inform the IRB of any amendment to the protocol in accordance with 
local requirements. The protocol must be re-approved by the IRB upon receipt of amendments and annually, if 
required per local regulations. 
Initial IRB approval, and all materials approved by the IRB for this study including the patient consent form and 
recruitment materials must be maintained by the Investigator and made available for inspection. 
12.2. Compliance and Ethical Conduct of the Study 
The Sponsor, Investigators, study staff, and designees will conduct the study in accordance with the protocol and 
with the following ethical principles that have their origin in the Declaration of Helsinki and are consistent with 
ICH, GCP, and other applicable local and federal laws, regulations, and guidelines. These include: 
•
Consensus ethical principles derived from international guidelines including the Declaration of Helsinki
and Council for International Organizations of Medical Sciences (CIOMS) International Ethical
Guidelines
•
International Conference on Harmonisation Good Clinical Practice (ICH GCP) and United States (US)
Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21
CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812
•
Applicable ICH E6 (R2) Good Clinical Practice (GCP) Guidelines and Human Subject Protection (HSP)
•
Applicable ISO20916 (In vitro diagnostic medical devices – Clinical performance studies using specimens
from human participants)
•
Good study practice standards
The investigator will be responsible for the following: 
•
Providing written summaries of the status of the study to the IRB/IEC annually or more frequently in
accordance with the requirements, policies, and procedures established by the IRB/IEC
•
Providing oversight of the conduct of the study at the site and adherence to requirements of 21 CFR, ICH
guidelines, the IRB/IEC, and all other applicable local regulations
In addition, the investigators and clinical study site staff who are responsible for the conduct, management, or 
oversight of this clinical trial must have completed Human Subjects Protection and ICH GCP Training.  
12.3. Regulatory Status 
The MSRC is a minimal risk device and is exempt from 21 CFR 812.2(c) IDE regulation. The test results of the 
Laboratory Developed Test being researched, developed, and validated in this study will not be returned to the 
Investigator, patient nor study sites. In addition, the device is:  
•
properly labeled in accordance with 21 CFR 809.10(c)
•
noninvasive and does not require invasive sampling procedure in accordance with 21 CFR 812.3(k) as the
test requires routine blood sampling that involves a simple venipuncture
•
not used as a diagnostic procedure without confirmation of the diagnosis by another, medically
established diagnostic product or procedure
12.4. Financial Disclosure 

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Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial information as 
requested to allow the sponsor to submit complete and accurate financial certification or disclosure statements to 
the appropriate regulatory authorities. Investigators are responsible for providing information on financial 
interests during the course of the study and for 1 year after completion of the study.  
13. Protocol Revision History
Rev. # 
Effective Date 
Summary of Changes 
1.0 
22-Feb-2024
Initial Release 
14. References
1.
Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi:
10.1038/nrdp.2018.1.
2.
Matcham F, Scott IC, Rayner L, et al. The impact of rheumatoid arthritis on quality-of-life assessed using the
SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014 Oct;44(2):123-30. doi:
10.1016/j.semarthrit.2014.05.001.
3.
Osterhaus JT, Purcaru O, Richard L. Discriminant validity, responsiveness and reliability of the rheumatoid
arthritis-specific Work Productivity Survey (WPS-RA). Arthritis Res Ther. 2009;11(3):R73. doi:
10.1186/ar2702.
4.
Verstappen SM, van Albada-Kuipers GA, et al. A good response to early DMARD treatment of patients with
rheumatoid arthritis in the first year predicts remission during follow up. Ann Rheum Dis. 2005 Jan;64(1):38-
43. doi: 10.1136/ard.2003.014928.
5.
Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the
TICORA study): a single-blind randomised controlled trial. Lancet. 2004; 364(9430):263–9. doi:
10.1016/S0140-6736(04)16676-2.
6.
Solomon DH, Bitton A, Katz JN, et al. Review: treat to target in rheumatoid arthritis: fact, fiction, or
hypothesis? Arthritis Rheumatol. 2014 Apr;66(4):775-82. doi: 10.1002/art.38323.
7.
Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the
Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. doi:
10.1002/acr.24596.
8.
Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid
arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis.
2020 Jun;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655.
9.
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the
Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1-26. doi: 10.1002/art.39480.
10. Mellors T, Withers JB, Ameli A, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification
of Response to Tumor Necrosis FactorInhibitor Therapies in Rheumatoid Arthritis Patients. Netw Syst
Med. 2020 July;3(1):91-104. doi:10.1089/nsm.2020.0007.
11. Cohen S, Wells AF, Curtis JR, et al. A Molecular Signature Response Classifier to Predict Inadequate
Response to Tumor Necrosis Factor-α Inhibitors: The NETWORK-004 Prospective Observational
Study. Rheumatol Ther. 2021 Sep;8(3):1159-1176. doi: 10.1007/s40744-021-00330-y.
12. Jones A, Rapisardo S, Zhang L, et al. Analytical and clinical validation of an RNA sequencing-based assay
for quantitative, accurate evaluation of a molecular signature response classifier in rheumatoid
arthritis. Expert Rev Mol Diagn. 2021 Nov;21(11):1235-1243. doi: 10.1080/14737159.2021.2000394.
13. Rendas-Baum R, Wallenstein GV, Koncz T, et al. Evaluating the efficacy of sequential biologic therapies for
rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res
Ther. 2011 Feb 16;13(1):R25. doi:10.1186/ar3249.
14. Incerti, D, Jansen, JP. A Description of the IVI-RA Model v2.0. 2020; last updated January 2020.
15. Kay J, Upchurch KS. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology (Oxford).
2012 Dec;51 Suppl 6:vi5-9. doi:10.1093/rheumatology/kes279.

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15. Appendix
15.1. List of Abbreviations and Key Terms
Abbreviation or 
Specialist Term 
Explanation 
ACR 
American College of Rheumatology 
AE 
Adverse event 
AATT 
Alternative approved targeted therapy 
altMOA 
Alternative mechanism of action (non-TNFi therapy) 
bDMARD 
Biologic disease modifying anti-rheumatic drug 
CCP 
Anti-cyclic citrullinated peptide antibodies 
CD20 
Cluster of differentiation 20 
CDAI 
Clinical disease activity index 
CRF 
Case report form 
CRP 
C-reactive protein
csDMARD 
Conventional synthetic disease-modifying antirheumatic drug 
CVAP 
Clinical Validation Analysis Plan 
DAS28 
Disease activity score, 28-joint version 
DMARD 
Disease modifying anti-rheumatic drug 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
EMR 
Electronic Medical Records 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
IEC 
Independent ethics committee 
IL-6 
Interleukin-6 
IRB 
Institutional Review Board 
JAK 
Janus kinase 
MSRC 
Molecular signature response classifier 
NSAID 
Non-steroidal anti-inflammatory drug 
RA 
Rheumatoid arthritis 
RAPID3 
Routine Assessment of Patient Index 3 
RF 
Rheumatoid factor 
RNA 
Ribonucleic acid 
Rx 
Treatment 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
TIM 
Targeted immune modulators 
TNFɑ 
Tumor necrosis factor alpha 

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TNFi 
Tumor necrosis factor inhibitor 
tsDMARD 
Targeted small molecule synthetic disease modifying anti-rheumatic drug 
T2T 
Treat to target 
UADE 
Unanticipated adverse device effect 
US 
United States 
15.2. Definitions 
Terms 
Definition of Terms 
Alternative Approved 
Targeted Therapy (AATT) 
Alternative approved targeted therapy is a protocol-defined 
pharmacologically active agent approved in the territory or region in 
which the patient is being treated (e.g., for rheumatoid arthritis) other 
than a TNFi agent. 
Baseline 
Assessments of patients as they enter the study. 
Endpoint 
Variable that pertains to the efficacy or safety evaluations of a study. 
Enrollment 
The point at which the patient a biologic or targeted therapy at Visit 2. 
Investigational period 
Period when major interests of protocol objectives are observed, when 
the intervention is given to a patient and that continues until the last 
assessment after the intervention. 
b/tsDMARD-naïve 
Patient has no history of initiating a biologic or targeted synthetic disease 
modifying antirheumatic drug (b/tsDMARD) at baseline (visit 1) 
including therapies from the following drug classes: TNFi (including 
TNFi biosimilars), JAKi, IL-1i, B-cell inhibitor, T-cell inhibitor, and IL-
6i 
csDMARD failure 
Patient treated with a csDMARD > 3 months and did not achieve an 
adequate response (low disease activity or remission)  
csDMARD 
contraindication 
Specific patient situations or factors that would make csDMARD therapy 
inadvisable to patient as it may be harmful (i.e., pregnancy, severe 
hypersensitivity, hepatotoxicity, etc.) 
csDMARD intolerance 
Inability for patient to tolerate adverse effects of csDMARD therapy (i.e., 
nausea, vomiting, abdominal pain, etc.) 
Comorbidity Active 
Patient has a condition (outlined in Section 8.1 Comorbidities) that is 
being treated and managed at the time of assessment visit. 
Comorbidity Inactive 
Patient has a history of a condition (outlined in Section 8.1 
Comorbidities) that is not being treated or managed at the time of 
assessment visit.  
Screening 
A process of active consideration of potential patients for enrollment in a 
study. 
Screen failure 
Potential patient who did not meet 1 or more criteria required for 
participation in a study. 
Screening period 
Period before entering the investigational period, usually from the time 
when a patient signs the consent until just before assigned therapy 
is given to a patient. 
Study period 
Period from the first site initiation to the last site completing the study. 
TNFi-exposed 
Patient has a history of initiating a TNFi therapy, did not reach treat-to-
target goals of low disease activity or remission by the time of baseline 
visit, has not initiated an altMOA therapy (non-TNFi therapy) prior to 
Visit 1, and is being considered for a change in b/tsDMARD therapy.  

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Treatment initiation 
The point at which a biologic or targeted therapy to treat RA is initiated. 
Variable 
Any entity that varies; any attribute, phenomenon or event that can have 
different qualitative or quantitative values. 
15.3. 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis 
The 2010 ACR/EULAR RA classification criteria below are intended to be applied to patients who present with 
definite swelling of at least one joint on clinical examination, for whom another diagnosis (e.g. SLE, PsA, gout) 
does not better account for the synovitis.15  
The points from each of domains A through D are added and the sum is considered to be the total score. A total 
score of >6 is needed to classify a patient as having definite RA.15  
Domain 
Category 
Point Score 
A 
Joint involvement (0-5 points)a 
1 large joint 
0 
2-10 large joints
1 
1-3 small joints (large joints not counted)
2 
4-10 small joints (large joints not counted)
3 
>10 joints including at least one small joint
5 
B 
Serology (at least one test needed for classification; 0-3 points)b 
Negative RF and negative ACPA 
0 
Low positive RF or low positive ACPA 
2 
High positive RF or high positive ACPA 
3 
C 
Acute-phase reactants (at least one test needed for classification; 0-1 point)c 
Normal CRP and normal ESR 
0 
Abnormal CRP or abnormal ESR 
1 
D 
Duration of symptomsd 
<6 weeks 
0 
>6 weeks
1 
aJoint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging 
evidence of synovitis. DIP joints, first CMC joints and first MTP joints are excluded from assessment. Large 
joints refers to shoulders, elbows, hips, knees and ankles. Small joints refers to MCP joints, PIP joints, second 
through fifth MTP joints, thumb IP joints and wrists. 
bNegative means less than or equal to the upper limit of normal (ULN); low positive means >ULN; high 
positive means >3× ULN. 
cNormal and abnormal are determined by local laboratory standards. 
dDuration of symptoms as per patient’s self-report. 

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15.4. 
Informed Consent Form (ICF) 
Informed Consent Form 
and Authorization to Use and Disclose Protected Health Information 
Sponsor / Study Title: 
PREDICT Therapy Selection for JAK, T-Cell, or IL-6 
Inhibitor Therapies, Using a Molecular Signature Response 
Classifier (PREDICT) 
Protocol Number: 
PREDCIT-001 
Principal Investigator: 
(Study Doctor) 
«PiFullName» 
Telephone: 
«IcfPhoneNumber» 
Address: 
«PiLocations» 
WHY IS THIS RESEARCH BEING DONE? 
This research is being done to make new tests, called precision medicine tests, that can help your doctor 
choose the medicine that is right for you and based on your own biology. Data collected in this study 
will be used to research, develop, and test whether a new test can predict which therapies you are most 
likely to respond to that are specific to your rheumatoid arthritis (RA) (Janus Kinase (JAK), T-Cell, and 
IL-6 inhibitor therapies). This future test being researched will help doctors decide which therapy is 
likely to work or not work but will not inform your current medical care.  
The information collected in this study will be taken from routine clinical assessments, your blood 
sample, medical records, and a few surveys the study staff will complete. Data collected from the study 
may be used for research, development, and testing that the lab test works. 
This is a prospective, multi-center-observational study conducted in the United States. This study does 
not involve any experimental drugs or devices. The study plans to enroll approximately 1,100 patients. 
Scipher Medicine is paying for this study. There is no cost to you to enroll and participate in this study. 
You will also have the option to authorize access to your future medical records and claims data solely 
related to your rheumatoid arthritis condition or other medical conditions after the conclusion of the 
study to help inform future research efforts. 
WHAT HAPPENS TO ME IF I AGREE TO TAKE PART IN THIS RESEARCH? 
Once you have consented to participate in the study by written signature, you can immediately start 
“Visit 1” study steps. These steps include the review of your medical history, health assessment 
questionnaires, and a blood draw. The reason for the blood draw is to run C-Reactive Protein (CRP) and 
anti-cyclic citrullinated peptide antibodies (anti-CCP) tests that will be used in the research study but 
results will not be returned to you nor used in your medical care. This study will require new tests for 
each blood draw since these can change with time. In addition, your blood will be used to look at your 
biology. This will be done by sequencing ribonucleic acid (RNA). RNA is the information your body 

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uses as the instructions to make proteins in your body. RNA and data collected in the study helps us 
predict which therapies are right for you. 
Your blood will be collected at Visit 1, Visit 3, and/or (if applicable) unscheduled visits: Change in 
Therapy and/or Blood Re-Draw. Unscheduled visits may occur if your  blood sample collected was not 
able to run all of the tests on it. Approximately 12 mL (1 tablespoon = 15mL) of blood will be drawn at 
study Visit 1 and 3, and/ or, if applicable, Unscheduled Visit: Change in Therapy and/ or Blood Re-
Draw, which is about 2.5% of what would be drawn if you were to donate your blood. 
For Visit 2, you will return or discuss over the phone with your study doctor which new biologic or 
targeted therapy you will start. The clinical care study team will review your health and medication 
history with you to identify any changes since Visit 1. They will also reaffirm your eligibility to go 
ahead with the study. You are not being instructed to try any investigational therapy. The therapy you 
start at Visit 2 will be the same if you were not in this research study. 
For Visit 3, this will occur approximately six months after starting your new biologic or targeted 
therapy. Every effort should be made so that Visit 3 occurs six months after starting treatment, but a date 
four weeks before or two weeks after the target six month visit will be accepted. After confirming you 
have been taking your medicine for the past six months, the same tests that were conducted on Visit 1 
will be repeated. These include the same health assessment questionnaires, collection of approximately 
12mL of blood for RNA testing, anti-CCP and CRP testing and a standard clinical evaluation (for 
example, swollen/tender joint counts). Your doctor may change your therapy during the study. If you 
switch to a therapy that is in the same category as what you started at Visit 2 you can remain in the 
study. If a new therapy from a different category is started before six months, you will complete the 
Unscheuled Visit: Change in Therapy and conclude the study. 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to participate in this study, you will complete 3 scheduled study-specified visits (Visit 1 = 
screening/baseline, Visit 2 = treatment initiation, and Visit 3 = 6 month follow-up or Unscheduled 
Therapy Change Visit) over the maximum span of 7 months, starting at the time that you complete Visit 
2.  
COULD BEING IN THIS STUDY HARM ME? 
This study does not involve any investigational drugs or devices, or medical procedures outside of your 
standard rheumatoid arthritis healthcare. Standard blood draws using a venipuncture procedure will be 
needed. This procedure will not be different from a standard blood draw done at your doctor’s office or 
laboratory. Though rare, you may experience slight bruising or discomfort at the site of the blood draw. 
Rarely, there may be an infection, or you may feel dizzy. 
Though your information will be kept confidential and private, there is a risk of loss of privacy. There 
may be risks which are currently unknown. 
WILL BEING IN THIS RESEARCH BENEFIT ME? 
There is no direct benefit to you by participating in this study. 
WILL IT COST ME MONEY TO TAKE PART IN THIS RESEARCH? 
This research study is intended to observe standard care of patients with RA. The study will not cover 
the cost of your RA management including treatments, standard of care labs or radiology tests that are 
ordered by your doctor. 

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IS PARTICIPATION IN THIS STUDY REQUIRED? 
Your participation in this study is completely voluntary. It is your choice whether to participate or not 
and you may change your mind and stop at any time. Choosing not to participate in the study or leaving 
the study after you join will not result in any penalty or loss of benefits to which you are otherwise 
entitled.  
 
If you decide to leave this study, contact your study doctor’s office as soon as possible so they can 
withdraw you from the study. Once you withdraw, no additional information will be collected from you.  
 
WHAT HAPPENS TO THE INFORMATION COLLECTED FOR THIS RESEARCH? 
All information that you provide will be kept strictly confidential. Other than your contact information 
and information needed to conduct the study, information collected about you throughout the study will 
not directly identify you once deidentified (meaning any personal information like name or address that 
can identify you will be removed) with unique study number. Information, such as your zip code will be 
collected and stored in a secure place and used only for research with the unique study number. 
 
Some of your information and medical records will be shared with individuals and organizations that 
conduct or watch over this research, including: 
• Sponsor 
• People who work with the Sponsor 
• Government agencies, such as the U.S. Food and Drug Administration (FDA) 
• Institutional Review Board (IRB)  
 
These people may look at your records to make sure the study has been done the right way. They also 
want to make sure that your health information has been collected the right way, or for other reasons that 
are allowed under the law. This means that absolute confidentiality cannot be guaranteed. 
 
We may publish or present the results of this research. However, any information that can identify you 
will be removed so your identity is protected.  
 
We protect your information from disclosure to others to the extent required by law. We cannot promise 
complete privacy as there is a risk of loss of confidentiality in registries, though the amount of private 
information shared will be the minimal amount needed to conduct the study. 
 
Data and specimens collected in this study might be deidentified and used for future research  and other 
efforts or distributed to other investigators or other third-parties without your knowledge. Future efforts 
may include conducting additional tests and discovering new markers that help diagnose, treat, or 
monitor diseases.  
 
While the precision medicine test uses RNA isolated from your blood samples to predict whether or not 
you are likely to respond to specific therapies (i.e., JAK, T-Cell, or IL-6 inhibitor therapy), DNA and 
Ribonucleic acid (RNA) isolated from your blood samples may also be used. Your blood sample and 
deidentified data may be used for research or commercial efforts. Your deidentified data and blood 
sample will be stored indefinitely or until the sample is exhausted following study completion.  
 
ALTERNATIVES TO PARTICIPATION  
The only alternative is to not participate in this study. 
 

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WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you have questions, concerns or complaints about the study, please contact the study 
doctor at the telephone number listed on the first page of this consent document.  
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research subjects. If you have any questions about your rights as a research subject, and/or concerns or 
complaints about this research study, contact: 
By mail 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
Or call toll free 
877-992-4724
Or by email 
adviser@advarra.com
Please reference the following number when contacting the Study Subject Adviser: PREDICT-001. 
WHAT IF I AM INJURED BECAUSE OF TAKING PART IN THIS STUDY? 
If you are injured or get sick because of procedures in this research, call your study doctor immediately. 
Your study doctor will provide emergency medical treatment. Your insurance may be billed for this 
treatment. The Sponsor will pay any charges that are not covered by your insurance policy or the 
government if the injury was not due to your underlying illness or condition and was not caused by you 
or some other third party. No other payment is routinely available from the study doctor or Sponsor. 
To pay medical expenses, the Sponsor may need to know information about you such as your name, date 
of birth, and Medicare Beneficiary Identifier (MBI). This is because the Sponsor must check to see if 
you receive Medicare and if you do, report the payment it makes to Medicare. 
WHAT IF NEW INFORMATION BECOMES AVAILABLE? 
We will tell you about any new information that may affect your health, welfare, or choice to stay in this 
research. 
CAN I BE REMOVED FROM THIS RESEARCH WITHOUT MY APPROVAL? 
The study doctor or the Sponsor of this research can remove you from this research without your 
approval. Possible reasons include: 
•
You knowingly provide false or misleading information
•
The study is cancelled by the Sponsor
The Sponsor or the IRB may decide to stop the study at any time. 
WILL I BE REIMBURSED FOR MY TIME TAKING PART IN THIS RESEARCH? 
You will be reimbursed for your time taking part in this research. You will be compensated the 
following amounts for each visit completed: $100 for Visit 1 (screening/ baseline), $50 for Visit 2 
(treatment initiation), $100 for Visit 3 (6 month follow-up) and/or, if applicable, $50 for each 
unscheduled visit.  
WHAT IF SOMETHING IS DEVELOPED FROM THIS RESEARCH? 
Your deidentified specimens and clinical data may be used for commercial profit. You will not receive a 
share in this commercial profit. 

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STATEMENT OF CONSENT: 
I have read and understand the information in this informed consent document. I have had an 
opportunity to ask questions and all of my questions have been answered to my satisfaction. I 
voluntarily agree to participate in this study until I decide otherwise. I do not give up any of my legal 
rights by signing and dating this consent document. I will receive a copy of this signed and dated 
consent document. 
______________________________________________________________________ 
Printed Name of Adult Subject Capable of Consent 
Date 
______________________________________________________________________ 
Signature of Adult Subject Capable of Consent 
Date 
______________________________________________________________________ 
Printed Name of Person Obtaining Consent 
Date 
______________________________________________________________________ 
Signature of Person Obtaining Consent 
Date 

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OPTION TO BE CONTACTED IN THE FUTURE 
The study staff and sponsor may want to contact you in the future. These are both optional. 
Do you give your permission for the investigator or staff to contact you regarding your willingness to 
participate in future research studies?            
    Yes 
   No  
Initials_________ 
Do you give your permission for the study staff or sponsor to contact you to receive periodic email/ 
mail* with health-related articles, tips, and educational resources relevant to your disease?    
*All relevant material will comply with relevant data privacy regulations such as HIPAA.
   Yes 
 
   No  
Initials_________ 
If yes to either or both, email, mailing address, and/or phone to be used for future contact 
Email: ________________________________________________________________ 
Mailing Address: 
(Street)_______________________________________________________________ 
(City) _______________________(State) _______________ (Zipcode)____________ 
Phone Number: ________________________________________________________ 
   Yes 
 
   No  
Initials_________ 

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AUTHORIZATION TO USE AND DISCLOSE 
PROTECTED HEALTH INFORMATION 
Federal privacy laws protect the use and release of your health information and related information that 
identifies you. We refer to this information as “health data.” Health data may include: 
•
Your name
•
Address (street, city, state, zip code)
•
Phone number
•
Date of birth
•
Medical history
•
Information from your study visits, including all test results.
If you enroll in the research study described in the informed consent form (above), the study doctor and 
study staff will use and share your health data with others as explained below. In addition, you hereby 
authorize your doctor to share your existing records with the study doctor and study staff. If you agree to 
the described uses and sharing of your health data, then after reading this entire document, please sign 
your name at the end on the line provided. If you have questions, you may ask the researcher who is 
reviewing the informed consent for the research with you or you can contact the researcher listed below.  
In this study, we may collect health data about you from: 
•
Past, present, and future medical records
•
Study records, including research office visits, tests, interviews, and questionnaires
Why will health data about you be used or shared with others? 
Your health data will be used to conduct and oversee the study, including for instance: 
•
To complete this research.
•
To evaluate the results of the study.
•
To check that the study is being done properly.
Who may see, use, and share your health data and why they may need to do so: 
For this study, the study staff may share health data about you with authorized users. Authorized users 
may include: 
•
Representatives of Scipher Medicine Corporation.
•
Representatives of Advarra IRB (an Institutional Review Board that reviews this study).
•
The Food and Drug Administration (FDA) and other US federal and state agencies.
•
Governmental agencies of other countries.
•
Outside individuals and companies, such as laboratories and data storage companies, that work
with the researchers and sponsor and need to access your information to conduct this study.
•
Other research doctors and medical centers participating in this study, if applicable.
•
A data safety monitoring board which oversees this study, if applicable.
Some people or groups who get your health data might not have to follow the same privacy rules that we 
follow and might use or share your health data without your permission in ways that are not described in 
this form. We share your health data only when we must, and we ask anyone who receives it from us to 
take measures to protect your privacy. However, once your identifiable information is shared, we cannot 
control all the ways that others use or share it and cannot promise that it will remain private. 
The results of this research study may be published in a medical journal or used to teach others. 

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However, your name or other identifiable information will not be used for these purposes without your 
specific permission. 
For how long will health data about me be used or shared with others? 
Because research is an ongoing process, we cannot give you an exact date when we will either destroy 
or stop using or sharing your health data. Your permission to use and share your health data does not 
expire. 
Your Privacy Rights 
You have the right not to sign this form that allows us to use and share your health data for research; 
however, if you don’t sign it, you can’t take part in this research study. Refusing to sign will not affect 
your present or future care and will not cause any penalty or loss of benefits to which you are otherwise 
entitled. 
You have the right to withdraw your permission for us to use or share your health data for this research 
study. If you want to withdraw your permission, you must notify the person at the following address: 
Client Services Representative 
500 Totten Pond Road, Floor 6 
Waltham, MA 02451 
(855) 724-7437 Opt. 2
client_services_team@scipher.com
Support@Scipher.com
Once permission is withdrawn, you cannot continue to take part in the study. If you withdraw your 
permission, no new health data that identifies you will be gathered after your written request is received. 
However, health data about you that as already been gathered may still be used and given to others as 
described in this form.  
If you decide not to sign and date this form, you will not be able to take part in the study. 
Optional Future Medical Record Release 
□By checking this box, you agree to allow your existing physician(s) to share and the sponsor, Scipher
Medicine Corporation, to access, use and share your future medical records and claims’ data related
solely to your rheumatoid arthritis condition or other medical conditions after the conclusion of the
study to help inform future research. This may include but is not limited to allowing access to your
future medical records and associated claims data as well as authorizing the identifiable pairing of your
healthcare data with study data and left-over blood samples on an ongoing basis. This permission can be
withdrawn at any time by notifying the person at the following address:
Client Services Representative 
500 Totten Pond Road, Floor 6 
Waltham, MA 02451 
(855) 724-7437 Opt. 2
client_services_team@scipher.com
Support@Scipher.com

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If you withdraw your permission, no new health data that identifies you will be gathered after your 
written request is received. However, health data about you that as already been gathered may still be 
used and given to others as described in this form.  
STATEMENT OF AUTHORIZATION 
I have read this form and its contents were explained. My questions have been answered. I voluntarily 
agree to allow study staff to collect, use and share my health data as specified in this form. I will receive 
a signed and dated copy of this form for my records. I am not giving up any of my legal rights by 
signing and dating this form.  
______________________________________________________________________ 
Printed Name of Subject 
______________________________________________________________________ 
Signature of Subject  
 
 
 
 
Date 

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15.5. 
CRF: Screening/ Baseline Visit (SBV) 

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15.6. 
CRF: Patient Reported Outcomes (PRO) 

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15.7. 
CRF: Treatment Initiation Visit (TI)  

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15.8. 
CRF: 24-week Follow-Up Visit  

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15.9. 
CRF: End of Study (EOS) 
 
 

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15.10. CRF: Unscheduled Visit: Change in Therapy (UVCT) 

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15.11. CRF: Unscheduled Visit: Blood Re-Draw  

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