Trial Outcomes & Findings for Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES) (NCT NCT03818737)

NCT ID: NCT03818737

Last Updated: 2023-07-27

Results Overview

Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the "no pain" anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 475 participants
• Primary outcome timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
• Results posted on: 2023-07-27

Participant Flow

Participants were recruited from Duke University in Durham, North Carolina, Sanford Health in Fargo, North Dakota, The Emory Clinic in Atlanta, Georgia, Sanford Health in Sioux Falls, South Dakota, and the Andrews Institute in Gulf Breeze, Florida, USA. Participant enrollment began March 28, 2019 and all follow-up was complete by May 31, 2022.

Participant milestones

Measure	Bone Marrow Derived Mesenchymal Stem Cells (MSCs) Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection Participants randomized to the bone marrow derived MSCs, adipose-derived MSCs, or umbilical cord tissue MSCs study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Overall Study STARTED	118	119	118	120
Overall Study Received Study Intervention	107	109	116	108
Overall Study COMPLETED	97	93	103	97
Overall Study NOT COMPLETED	21	26	15	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)

Baseline characteristics by cohort

Measure	Bone Marrow Derived MSCs n=118 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=119 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=118 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=120 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.	Total n=475 Participants Total of all reporting groups
Age, Continuous	58.6 years STANDARD_DEVIATION 7.33 • n=5 Participants	58.2 years STANDARD_DEVIATION 7.31 • n=7 Participants	57.9 years STANDARD_DEVIATION 8.18 • n=5 Participants	58.3 years STANDARD_DEVIATION 8.05 • n=4 Participants	58.3 years STANDARD_DEVIATION 7.71 • n=21 Participants
Age, Customized Categorical age · 40 to 59 years of age	57 Participants n=5 Participants	63 Participants n=7 Participants	64 Participants n=5 Participants	62 Participants n=4 Participants	246 Participants n=21 Participants
Age, Customized Categorical age · 60 to 70 years of age	61 Participants n=5 Participants	56 Participants n=7 Participants	54 Participants n=5 Participants	58 Participants n=4 Participants	229 Participants n=21 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	63 Participants n=7 Participants	65 Participants n=5 Participants	71 Participants n=4 Participants	261 Participants n=21 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	56 Participants n=7 Participants	53 Participants n=5 Participants	49 Participants n=4 Participants	214 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	116 Participants n=5 Participants	113 Participants n=7 Participants	113 Participants n=5 Participants	114 Participants n=4 Participants	456 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	57 Participants n=21 Participants
Race (NIH/OMB) White	92 Participants n=5 Participants	99 Participants n=7 Participants	102 Participants n=5 Participants	104 Participants n=4 Participants	397 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	118 Participants n=5 Participants	119 Participants n=7 Participants	118 Participants n=5 Participants	120 Participants n=4 Participants	475 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Population: This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.

Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the "no pain" anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.

Outcome measures

Measure	Bone Marrow Derived MSCs n=101 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=102 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=111 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=101 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Change in Visual Analog Pain Scale (VAS-pain) Score Absolute Change from Baseline at Month 3	-28.8 units on a scale Standard Error 2.54	-17.8 units on a scale Standard Error 2.48	-17.3 units on a scale Standard Error 2.43	-21.1 units on a scale Standard Error 2.49
Change in Visual Analog Pain Scale (VAS-pain) Score Absolute Change from Baseline at Month 1	-20.2 units on a scale Standard Error 2.52	-15.9 units on a scale Standard Error 2.48	-16.7 units on a scale Standard Error 2.40	-25.2 units on a scale Standard Error 2.49
Change in Visual Analog Pain Scale (VAS-pain) Score Absolute Change from Baseline at Month 6	-23.2 units on a scale Standard Error 2.56	-21.6 units on a scale Standard Error 2.53	-19.7 units on a scale Standard Error 2.47	-22.7 units on a scale Standard Error 2.51
Change in Visual Analog Pain Scale (VAS-pain) Score Absolute Change from Baseline at Month 9	-21.9 units on a scale Standard Error 2.64	-17.9 units on a scale Standard Error 2.63	-16.5 units on a scale Standard Error 2.58	-23.3 units on a scale Standard Error 2.63
Change in Visual Analog Pain Scale (VAS-pain) Score Absolute Change from Baseline at Month 12	-25.5 units on a scale Standard Error 2.56	-19.9 units on a scale Standard Error 2.55	-20.6 units on a scale Standard Error 2.48	-22.3 units on a scale Standard Error 2.51

PRIMARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Population: This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.

The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.

Outcome measures

Measure	Bone Marrow Derived MSCs n=101 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=101 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=111 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=101 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score Absolute Change from Baseline at Month 6	18.1 score on a scale Standard Error 1.88	17.2 score on a scale Standard Error 1.87	15.4 score on a scale Standard Error 1.81	18.6 score on a scale Standard Error 1.85
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score Absolute Change from Baseline at Month 1	15.5 score on a scale Standard Error 1.85	15.4 score on a scale Standard Error 1.84	11.5 score on a scale Standard Error 1.77	19.2 score on a scale Standard Error 1.83
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score Absolute Change from Baseline at Month 3	19.2 score on a scale Standard Error 1.86	16.8 score on a scale Standard Error 1.84	12.8 score on a scale Standard Error 1.79	18.7 score on a scale Standard Error 1.83
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score Absolute Change from Baseline at Month 9	16.2 score on a scale Standard Error 193	14.7 score on a scale Standard Error 1.93	13.9 score on a scale Standard Error 1.88	16.3 score on a scale Standard Error 1.92
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score Absolute Change from Baseline at Month 12	18.9 score on a scale Standard Error 1.88	17.3 score on a scale Standard Error 1.88	16.4 score on a scale Standard Error 1.81	18.5 score on a scale Standard Error 1.85

SECONDARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Population: This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. This analysis includes participants who had complete information for each subscale of the KOOS questionnaire, allowing for calculation of the total KOOS score.

The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.

Outcome measures

Measure	Bone Marrow Derived MSCs n=100 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=95 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=109 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=101 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score Change from Baseline at Month 1	14.48 score on a scale Standard Deviation 14.95	14.34 score on a scale Standard Deviation 12.40	11.14 score on a scale Standard Deviation 12.47	17.70 score on a scale Standard Deviation 14.65
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score Change from Baseline at Month 3	18.63 score on a scale Standard Deviation 15.32	16.30 score on a scale Standard Deviation 16.02	13.85 score on a scale Standard Deviation 14.36	17.21 score on a scale Standard Deviation 16.97
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score Change from Baseline at Month 6	18.39 score on a scale Standard Deviation 16.96	17.53 score on a scale Standard Deviation 16.23	15.62 score on a scale Standard Deviation 14.66	17.44 score on a scale Standard Deviation 17.47
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score Change from Baseline at Month 9	14.17 score on a scale Standard Deviation 18.87	13.36 score on a scale Standard Deviation 16.91	13.96 score on a scale Standard Deviation 15.83	116.30 score on a scale Standard Deviation 18.54
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score Change from Baseline at Month 12	18.52 score on a scale Standard Deviation 18.93	17.61 score on a scale Standard Deviation 19.70	17.49 score on a scale Standard Deviation 18.34	19.27 score on a scale Standard Deviation 18.54

SECONDARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Population: This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.

The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being "no problem" and 3 being "most extreme problem"). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.

Outcome measures

Measure	Bone Marrow Derived MSCs n=100 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=101 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=111 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=100 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Change in EuroQuality of Life (EQ-5D-3L) Index Score Absolute Change from Baseline at Month 12	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01
Change in EuroQuality of Life (EQ-5D-3L) Index Score Absolute Change from Baseline at Month 1	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01
Change in EuroQuality of Life (EQ-5D-3L) Index Score Absolute Change from Baseline at Month 3	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01
Change in EuroQuality of Life (EQ-5D-3L) Index Score Absolute Change from Baseline at Month 6	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01	0.1 score on a scale Standard Error 0.01
Change in EuroQuality of Life (EQ-5D-3L) Index Score Absolute Change from Baseline at Month 9	0.0 score on a scale Standard Error 0.02	0.1 score on a scale Standard Error 0.02	0.1 score on a scale Standard Error 0.02	0.1 score on a scale Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Population: This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. Participants with incomplete responses are not included in the analysis for that domain.

The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.

Outcome measures

Measure	Bone Marrow Derived MSCs n=114 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=115 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=116 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=116 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Month 1	44.3 t-score Standard Deviation 6.54	43.8 t-score Standard Deviation 6.19	44.9 t-score Standard Deviation 5.97	45.0 t-score Standard Deviation 6.92
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Baseline	47.1 t-score Standard Deviation 7.89	47.5 t-score Standard Deviation 7.79	47.1 t-score Standard Deviation 7.31	48.2 t-score Standard Deviation 8.69
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Month 1	45.9 t-score Standard Deviation 7.46	45.4 t-score Standard Deviation 7.64	45.9 t-score Standard Deviation 7.73	45.4 t-score Standard Deviation 7.83
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Month 3	45.1 t-score Standard Deviation 7.34	45.4 t-score Standard Deviation 7.91	45.4 t-score Standard Deviation 7.15	45.5 t-score Standard Deviation 7.67
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Month 6	45.9 t-score Standard Deviation 7.45	45.8 t-score Standard Deviation 8.23	45.2 t-score Standard Deviation 7.51	45.3 t-score Standard Deviation 6.66
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Month 9	46.1 t-score Standard Deviation 8.04	45.4 t-score Standard Deviation 7.94	44.9 t-score Standard Deviation 6.53	45.1 t-score Standard Deviation 6.88
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Anxiety Score - Month 12	45.6 t-score Standard Deviation 8.10	45.3 t-score Standard Deviation 7.46	44.9 t-score Standard Deviation 7.25	45.2 t-score Standard Deviation 8.09
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Baseline	44.7 t-score Standard Deviation 5.70	45.0 t-score Standard Deviation 6.56	44.9 t-score Standard Deviation 6.34	45.6 t-score Standard Deviation 7.61
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Month 3	43.8 t-score Standard Deviation 5.56	44.0 t-score Standard Deviation 6.46	44.4 t-score Standard Deviation 5.88	446 t-score Standard Deviation 6.60
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Month 6	43.9 t-score Standard Deviation 5.98	44.9 t-score Standard Deviation 6.50	44.0 t-score Standard Deviation 5.44	44.0 t-score Standard Deviation 5.38
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Month 9	45.6 t-score Standard Deviation 6.99	45.2 t-score Standard Deviation 6.71	43.4 t-score Standard Deviation 5.03	44.1 t-score Standard Deviation 5.78
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Depression Score - Month 12	44.5 t-score Standard Deviation 6.33	43.9 t-score Standard Deviation 6.01	44.3 t-score Standard Deviation 6.05	44.5 t-score Standard Deviation 6.65
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Baseline	46.8 t-score Standard Deviation 8.35	47.0 t-score Standard Deviation 8.29	47.7 t-score Standard Deviation 7.39	48.5 t-score Standard Deviation 8.92
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Month 1	45.8 t-score Standard Deviation 8.94	45.8 t-score Standard Deviation 8.96	46.9 t-score Standard Deviation 8.45	46.2 t-score Standard Deviation 8.55
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Month 3	45.0 t-score Standard Deviation 9.35	45.3 t-score Standard Deviation 8.50	46.0 t-score Standard Deviation 7.86	44.8 t-score Standard Deviation 8.50
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Month 6	45.9 t-score Standard Deviation 9.52	46.1 t-score Standard Deviation 8.77	44.9 t-score Standard Deviation 8.57	45.1 t-score Standard Deviation 8.30
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Month 9	46.7 t-score Standard Deviation 9.39	46.1 t-score Standard Deviation 8.98	47.1 t-score Standard Deviation 8.35	46.8 t-score Standard Deviation 9.70
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Fatigue Score - Month 12	45.6 t-score Standard Deviation 9.09	45.2 t-score Standard Deviation 8.26	45.9 t-score Standard Deviation 8.66	45.3 t-score Standard Deviation 9.84
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Baseline	59.1 t-score Standard Deviation 6.06	58.6 t-score Standard Deviation 6.72	58.9 t-score Standard Deviation 5.58	60.4 t-score Standard Deviation 6.56
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Month 1	53.6 t-score Standard Deviation 7.76	52.5 t-score Standard Deviation 6.82	54.8 t-score Standard Deviation 7.98	53.3 t-score Standard Deviation 7.81
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Month 3	51.6 t-score Standard Deviation 8.17	52.1 t-score Standard Deviation 7.42	52.5 t-score Standard Deviation 7.86	53.5 t-score Standard Deviation 8.72
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Month 6	51.5 t-score Standard Deviation 8.80	51.5 t-score Standard Deviation 8.00	51.9 t-score Standard Deviation 7.71	53.6 t-score Standard Deviation 7.67
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Month 9	52.4 t-score Standard Deviation 8.55	52.3 t-score Standard Deviation 8.21	51.8 t-score Standard Deviation 8.14	53.2 t-score Standard Deviation 8.77
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Pain Score - Month 12	51.5 t-score Standard Deviation 8.47	50.8 t-score Standard Deviation 8.23	51.2 t-score Standard Deviation 8.26	52.7 t-score Standard Deviation 8.48
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Baseline	39.3 t-score Standard Deviation 5.30	40.3 t-score Standard Deviation 5.80	38.8 t-score Standard Deviation 4.04	38.3 t-score Standard Deviation 5.10
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Month 1	43.0 t-score Standard Deviation 7.30	43.6 t-score Standard Deviation 5.48	41.9 t-score Standard Deviation 6.07	43.3 t-score Standard Deviation 6.12
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Month 3	44.9 t-score Standard Deviation 7.77	44.3 t-score Standard Deviation 5.84	43.8 t-score Standard Deviation 6.81	42.9 t-score Standard Deviation 7.03
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Month 6	44.5 t-score Standard Deviation 7.33	45.2 t-score Standard Deviation 6.72	44.2 t-score Standard Deviation 6.59	43.0 t-score Standard Deviation 6.15
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Month 9	43.0 t-score Standard Deviation 7.32	44.6 t-score Standard Deviation 6.60	44.4 t-score Standard Deviation 7.17	43.0 t-score Standard Deviation 6.76
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Physical Function Score - Month 12	44.4 t-score Standard Deviation 7.81	45.2 t-score Standard Deviation 7.20	44.8 t-score Standard Deviation 7.25	43.6 t-score Standard Deviation 6.84
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Baseline	48.9 t-score Standard Deviation 7.00	49.7 t-score Standard Deviation 7.74	50.1 t-score Standard Deviation 7.92	50.2 t-score Standard Deviation 8.07
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Month 1	47.2 t-score Standard Deviation 7.48	48.4 t-score Standard Deviation 7.63	48.3 t-score Standard Deviation 8.66	49.2 t-score Standard Deviation 7.91
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Month 3	47.3 t-score Standard Deviation 7.94	48.3 t-score Standard Deviation 7.85	47.8 t-score Standard Deviation 7.90	47.9 t-score Standard Deviation 8.18
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Month 6	48.6 t-score Standard Deviation 8.31	48.9 t-score Standard Deviation 6.88	48.1 t-score Standard Deviation 7.89	48.9 t-score Standard Deviation 7.38
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Month 9	48.9 t-score Standard Deviation 7.50	48.5 t-score Standard Deviation 7.35	48.9 t-score Standard Deviation 7.77	47.9 t-score Standard Deviation 8.17
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Sleep Disturbance Score - Month 12	47.8 t-score Standard Deviation 8.42	49.0 t-score Standard Deviation 7.02	48.7 t-score Standard Deviation 8.05	48.8 t-score Standard Deviation 8.08
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Baseline	49.5 t-score Standard Deviation 8.24	47.9 t-score Standard Deviation 8.33	48.2 t-score Standard Deviation 7.18	46.9 t-score Standard Deviation 7.53
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Month 1	52.1 t-score Standard Deviation 8.69	51.6 t-score Standard Deviation 7.83	51.0 t-score Standard Deviation 7.65	51.5 t-score Standard Deviation 8.30
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Month 3	54.4 t-score Standard Deviation 9.36	53.3 t-score Standard Deviation 8.18	52.4 t-score Standard Deviation 8.25	51.6 t-score Standard Deviation 9.00
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Month 6	53.1 t-score Standard Deviation 8.77	52.7 t-score Standard Deviation 8.32	52.3 t-score Standard Deviation 8.15	52.0 t-score Standard Deviation 8.56
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Month 9	53.6 t-score Standard Deviation 9.02	52.6 t-score Standard Deviation 8.41	52.8 t-score Standard Deviation 8.33	52.4 t-score Standard Deviation 8.47
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Social Roles and Activities Score - Month 12	53.3 t-score Standard Deviation 9.02	53.5 t-score Standard Deviation 8.51	53.6 t-score Standard Deviation 8.05	52.2 t-score Standard Deviation 8.30

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: This analysis includes participants who successfully completed the MRI assessment at the indicated study visit. Some participants withdrew from the study prior to reaching study visits where the MRI was conducted. Some participants who attended the MRI visit were not able to hold still during the entire MRI and an accurate measurement could not be obtained.

An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.

Outcome measures

Measure	Bone Marrow Derived MSCs n=103 Participants Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=107 Participants Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=108 Participants Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=101 Participants Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Overall MRI Grade of Osteoarthritis Baseline	40.5 score on a scale Standard Deviation 6.19	39.7 score on a scale Standard Deviation 7.82	38.2 score on a scale Standard Deviation 7.77	38.9 score on a scale Standard Deviation 7.70
Overall MRI Grade of Osteoarthritis Month 6	40.4 score on a scale Standard Deviation 6.27	39.3 score on a scale Standard Deviation 7.55	38.3 score on a scale Standard Deviation 7.86	39.3 score on a scale Standard Deviation 7.88
Overall MRI Grade of Osteoarthritis Month 12	40.8 score on a scale Standard Deviation 6.01	39.8 score on a scale Standard Deviation 7.76	37.6 score on a scale Standard Deviation 7.81	39.0 score on a scale Standard Deviation 7.84

Adverse Events

Bone Marrow Derived MSCs

Serious events: 8 serious events

Other events: 53 other events

Deaths: 0 deaths

Adipose-derived MSCs

Serious events: 2 serious events

Other events: 64 other events

Deaths: 0 deaths

Umbilical Cord Tissue (UCT) MSCs

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Corticosteroid Injection

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bone Marrow Derived MSCs n=107 participants at risk Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=109 participants at risk Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=116 participants at risk Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=108 participants at risk Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic breast cancer	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.92% 1/109 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.86% 1/116 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Cardiac disorders Acute myocardial infarction	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angina pectoris	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Congenital, familial and genetic disorders Atrial fibrillation	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Cardiac disorders Myocardial infarction	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.86% 1/116 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Gastrointestinal disorders Large intestine perforation	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Hepatobiliary disorders Cholecystitis	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Infections and infestations Appendicitis	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	1.9% 2/108 • Number of events 2 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Infections and infestations Clostridium difficile colitis	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Infections and infestations Abdominal abscess	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Infections and infestations Sepsis	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Traumatic pneumothorax	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.86% 1/116 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Nervous system disorders Ischemic stroke	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.92% 1/109 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Nervous system disorders Migraine	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Nervous system disorders Partial seizures	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.86% 1/116 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Nervous system disorders Radiculopathy	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Renal and urinary disorders Nephrolithiasis	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.93% 1/108 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Vascular disorders Hypertension urgency	0.93% 1/107 • Number of events 1 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.

Other adverse events

Measure	Bone Marrow Derived MSCs n=107 participants at risk Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).	Adipose-derived MSCs n=109 participants at risk Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).	Umbilical Cord Tissue (UCT) MSCs n=116 participants at risk Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.	Corticosteroid Injection n=108 participants at risk Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.
Musculoskeletal and connective tissue disorders Arthralgia	25.2% 27/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	22.9% 25/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	25.9% 30/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	25.9% 28/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Musculoskeletal and connective tissue disorders Joint stiffness	12.1% 13/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	5.5% 6/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	6.9% 8/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	7.4% 8/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Musculoskeletal and connective tissue disorders Joint swelling	17.8% 19/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	14.7% 16/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	24.1% 28/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	7.4% 8/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Post procedural contusion	10.3% 11/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	37.6% 41/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	19.4% 21/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Post procedural haematoma	2.8% 3/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	11.0% 12/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	6.5% 7/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.
Injury, poisoning and procedural complications Procedural pain	26.2% 28/107 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	33.9% 37/109 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	0.00% 0/116 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.	24.1% 26/108 • Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.

Additional Information

Kenneth Mautner, MD

Emory University

Phone: 404-778-7142

Email: kmautne@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place