Trial Outcomes & Findings for Anti-TNF Agents for the Treatment of Rheumatoid Arthritis (NCT NCT00837434)

Last Updated: 2021-09-22

Results Overview

Analysis of the steady state composition of the B cell compartment were performed using ex-vivo multicolor flow cytometry on Ficoll isolated peripheral blood mononuclear cells (PBMCs). CD27+ switched memory B cells are a subset of B cells and are assessed by flow cytometry. CD27+ switched memory B cells are expressed as a percent of B cells. Lower CD27+ memory B cells indicate a decrease in the generation of B cell memory which may be caused by blocking lymphotoxin (LT) and tumor necrosis factor (TNF) signaling.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

63 participants

Primary outcome timeframe

Week 12

Results posted on

2021-09-22

Participant Flow

Participants were to be recruited from seven sites in the United States. Recruitment occurred at six sites. The first site was activated in April 2009. The first participant was randomized in July 2009 and the last participant was randomized in July 2013.

Participant milestones

Participant milestones
Measure	Etanercept Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Overall Study STARTED	43	20
Overall Study COMPLETED	34	19
Overall Study NOT COMPLETED	9	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Etanercept Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Overall Study Physician Decision	3	0
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawn by sponsor/regulatory agency	1	0
Overall Study Noncompliant	2	0
Overall Study Baseline assessments not done in time	1	0
Overall Study Unable to obtain study drug	1	0

Baseline Characteristics

Anti-TNF Agents for the Treatment of Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etanercept n=39 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.	Total n=58 Participants Total of all reporting groups
Age, Continuous	51.7 years STANDARD_DEVIATION 9.4 • n=99 Participants	52.7 years STANDARD_DEVIATION 14.0 • n=107 Participants	52.0 years STANDARD_DEVIATION 11.0 • n=206 Participants
Sex: Female, Male Female	31 Participants n=99 Participants	15 Participants n=107 Participants	46 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	4 Participants n=107 Participants	12 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=99 Participants	1 Participants n=107 Participants	9 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=99 Participants	18 Participants n=107 Participants	49 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	5 Participants n=99 Participants	1 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) White	30 Participants n=99 Participants	18 Participants n=107 Participants	48 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants	0 Participants n=107 Participants	4 Participants n=206 Participants
Region of Enrollment United States	39 participants n=99 Participants	19 participants n=107 Participants	58 participants n=206 Participants
Detection of Either IgM-Rheumatoid Factor or Antibodies to Cyclic Citrullinated Peptide Positive	30 participants n=99 Participants	14 participants n=107 Participants	44 participants n=206 Participants
Detection of Either IgM-Rheumatoid Factor or Antibodies to Cyclic Citrullinated Peptide Negative	9 participants n=99 Participants	5 participants n=107 Participants	14 participants n=206 Participants
Detection of IgM-Rheumatoid Factor (IgM RF) Positive	24 participants n=99 Participants	9 participants n=107 Participants	33 participants n=206 Participants
Detection of IgM-Rheumatoid Factor (IgM RF) Negative	15 participants n=99 Participants	10 participants n=107 Participants	25 participants n=206 Participants
Detection of Antibodies to Cyclic Citrullinated Antibody Peptide Positive	25 participants n=99 Participants	11 participants n=107 Participants	36 participants n=206 Participants
Detection of Antibodies to Cyclic Citrullinated Antibody Peptide Negative	14 participants n=99 Participants	8 participants n=107 Participants	22 participants n=206 Participants
Methotrexate Dosage	17.4 mg STANDARD_DEVIATION 4.0 • n=99 Participants	18.8 mg STANDARD_DEVIATION 3.8 • n=107 Participants	17.9 mg STANDARD_DEVIATION 3.9 • n=206 Participants
Years with Rheumatoid Arthritis	5.8 years STANDARD_DEVIATION 7.7 • n=99 Participants	4.3 years STANDARD_DEVIATION 5.2 • n=107 Participants	5.3 years STANDARD_DEVIATION 7.0 • n=206 Participants
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	1.4 scores on a scale STANDARD_DEVIATION 0.7 • n=99 Participants	1.3 scores on a scale STANDARD_DEVIATION 0.6 • n=107 Participants	1.4 scores on a scale STANDARD_DEVIATION 0.7 • n=206 Participants
C-reactive Protein (CRP) Level	14.1 mg/L STANDARD_DEVIATION 25.5 • n=99 Participants	13.3 mg/L STANDARD_DEVIATION 24.3 • n=107 Participants	13.8 mg/L STANDARD_DEVIATION 24.9 • n=206 Participants
Tender Joint Count	12.2 Joints STANDARD_DEVIATION 6.6 • n=99 Participants	12.6 Joints STANDARD_DEVIATION 7.2 • n=107 Participants	12.3 Joints STANDARD_DEVIATION 6.7 • n=206 Participants
Swollen Joint Count at Baseline	9.9 Joints STANDARD_DEVIATION 6.2 • n=99 Participants	9.4 Joints STANDARD_DEVIATION 5.9 • n=107 Participants	9.7 Joints STANDARD_DEVIATION 6.0 • n=206 Participants
Patient's Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS)	5.9 cm STANDARD_DEVIATION 2.6 • n=99 Participants	7.3 cm STANDARD_DEVIATION 2.0 • n=107 Participants	6.4 cm STANDARD_DEVIATION 2.5 • n=206 Participants
Disease Activity Score Using C-reactive Protein (DAS28-CRP)	5.2 scores on a scale STANDARD_DEVIATION 1.0 • n=99 Participants	5.4 scores on a scale STANDARD_DEVIATION 0.7 • n=107 Participants	5.3 scores on a scale STANDARD_DEVIATION 0.9 • n=206 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The Per Protocol population includes subjects with a baseline and week 12 (plus or minus 1 week) assessment that received at least 75% of the planned doses of either etanercept or adalimumab prior to week 12 and who did not have any serious protocol deviations.

Outcome measures

Outcome measures
Measure	Etanercept n=30 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=18 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of CD27+ Switched Memory B Cells at Week 12	13.2 Percentage of B Cells Standard Deviation 7.3	13.8 Percentage of B Cells Standard Deviation 7.2

SECONDARY outcome

Timeframe: Week 12

Population: The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for two participants who received Etanercept.

Good responders: change in DAS28-CRP (Baseline-Week12) \> 1.2 and Week 12 DAS-CRP score was \<\\= 3.2. If the conditions for non-response\* or good response were not met, the DAS28-CRP response was considered moderate. Participants with measurements for designated time points were included in the analysis. \[\*Non-responders had any of 4 conditions: change in DAS28-CRP (Baseline -Week 12) \<0.6; 0.6 \<\\= change in DAS28-CRP ( Baseline-Week 12) \< 1.2 with Week 12 DAS28-CRP score \> 5.1; a flare that required prednisone \> 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to \<\\= 10 mg/day by Week 8; or the participant required prednisone \> 20 mg/day at any time point\].

Outcome measures

Outcome measures
Measure	Etanercept n=37 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 12	86.5 percentage of participants	89.5 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Good responders had: change in DAS28-CRP (Baseline-Week 24) \> 1.2 and the Week 24 DAS-CRP score was \<= 3.2. If the conditions for non-response\* or good response were not met then the DAS28-CRP response was considered moderate.\[\*Non-responders had any of the 4 conditions: change in DAS28-CRP (Baseline -Week 24) \<0.6; 0.6 \<\\= change in DAS28-CRP ( Baseline-Week 24) \< 1.2 with Week 24 DAS28-CRP score \> 5.1 ; a flare that required prednisone \> 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to \<= 10 mg/day by Week 8; or the participant required prednisone \> 20 mg/day at any time point\]. Participants with measurements for designated time points were included in the analysis.

Outcome measures

Outcome measures
Measure	Etanercept n=34 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 24	88.2 percentage of participants	84.2 percentage of participants

SECONDARY outcome

Timeframe: Week 12

The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures: * Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

Outcome measures

Outcome measures
Measure	Etanercept n=37 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Meeting ACR20 Response Criteria at Week 12	67.6 percentage of participants	73.7 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Etanercept n=34 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Meeting ACR20 Response Criteria at Week 24	73.5 percentage of participants	84.2 percentage of participants

SECONDARY outcome

Timeframe: Week 12

The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures: * Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

Outcome measures

Outcome measures
Measure	Etanercept n=37 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Meeting ACR50 Response Criteria at Week 12	29.7 percentage of participants	47.4 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Etanercept n=34 Participants Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 Participants Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Percentage of Participants Meeting ACR50 Response Criteria at Week 24	38.2 percentage of participants	63.2 percentage of participants

Adverse Events

Etanercept

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Adalimumab

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Etanercept n=39 participants at risk Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 participants at risk Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.6% 1/39 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	0.00% 0/19 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/39 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Psychiatric disorders Suicide attempt	2.6% 1/39 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	0.00% 0/19 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.

Other adverse events

Additional Information

Director, Clinical Research Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Etanercept n=39 participants at risk Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Adalimumab n=19 participants at risk Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Blood and lymphatic system disorders Anaemia	23.1% 9/39 • Number of events 9 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	15.8% 3/19 • Number of events 3 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Blood and lymphatic system disorders Leukopenia	10.3% 4/39 • Number of events 7 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	10.5% 2/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Blood and lymphatic system disorders Lymphopenia	12.8% 5/39 • Number of events 5 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	15.8% 3/19 • Number of events 5 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Blood and lymphatic system disorders Neutropenia	7.7% 3/39 • Number of events 5 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Gastrointestinal disorders Nausea	5.1% 2/39 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
General disorders Fatigue	2.6% 1/39 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	10.5% 2/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Infections and infestations Bronchitis	10.3% 4/39 • Number of events 4 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	10.5% 2/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Infections and infestations Gastroenteritis	5.1% 2/39 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Infections and infestations Nasopharyngitis	10.3% 4/39 • Number of events 4 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	15.8% 3/19 • Number of events 4 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Infections and infestations Upper respiratory tract infection	10.3% 4/39 • Number of events 5 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Investigations Alanine aminotransferase increased	17.9% 7/39 • Number of events 9 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	21.1% 4/19 • Number of events 4 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Investigations Aspartate aminotransferase increased	25.6% 10/39 • Number of events 12 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	15.8% 3/19 • Number of events 3 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Investigations Blood creatinine increased	12.8% 5/39 • Number of events 6 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Musculoskeletal and connective tissue disorders Arthralgia	12.8% 5/39 • Number of events 5 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Musculoskeletal and connective tissue disorders Back pain	7.7% 3/39 • Number of events 3 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	0.00% 0/19 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Musculoskeletal and connective tissue disorders Pain in extremity	12.8% 5/39 • Number of events 6 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	10.5% 2/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Nervous system disorders Headache	15.4% 6/39 • Number of events 6 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 3/39 • Number of events 3 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	0.00% 0/19 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Skin and subcutaneous tissue disorders Dermatitis contact	7.7% 3/39 • Number of events 3 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	0.00% 0/19 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Skin and subcutaneous tissue disorders Rash	10.3% 4/39 • Number of events 4 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	10.5% 2/19 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Vascular disorders Hypertension	5.1% 2/39 • Number of events 2 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.	5.3% 1/19 • Number of events 1 • From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.