PROGRESS II: APSS-33-00: A Multicenter, Pilot Study of Autologous Protein Solution (APS) in Knee Osteoarthritis (OA)

• Sponsor: Zimmer Biomet (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02138890
• Collaborator: (none)
• Enrollment: 46
• Locations: 4
• Arms: 2
• Duration (Months): 76.5
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This double-blind, multicenter, randomized, controlled trial (RCT) will evaluate the efficacy of a single dose of Autologous Protein Solution (APS) in patients with osteoarthritis (OA) of the knee who have failed at least 1 conservative osteoarthritis (OA) therapy (e.g. physiotherapy, simple analgesics, intra-articular injection).

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Device: APS; Device: Saline	N/A

Detailed Description

A double-blind, multicenter, randomized, controlled trial (RCT) that will evaluate the efficacy of a single dose of Autologous Protein Solution (APS) in patients with Osteoarthritis (OA) of the knee who have failed at least 1 conservative OA therapy (e.g. physiotherapy, simple analgesics, intra-articular injection).

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Study of a Single, Intra-Articular Injection of Autologous Protein Solution (APS) in Patients With Osteoarthritis (OA) of the Knee
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Sep 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: APS injection Autologous Protein Solution	Device: APS; Intra-articular Injection
Placebo Comparator: Control Saline	Device: Saline; Intra-articular injection

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 6 Months in Pain Measured With WOMAC Questionnaire (Day 1, Week 2, Month 1, 3 and 6) [6 months]

   The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC pain subscale consisted of five questions scored from 0 to 4. The pain has a range of 0 (no pain) to 20 (maximal pain).

2. Pain Measured With WOMAC Questionnaire Subscale Pain at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months. [12 Months]

   The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC pain subscale consisted of five questions scored from 0 to 4. The pain has a range of 0 (no pain) to 20 (maximal pain).

Secondary Outcome Measures

1. Pain Measured With Visual Analogue Scale at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 Months]

   The Visual Analogue Scale is a common tool for measuring general pain. A 100 mm line is marked from 0 to 10 in 10 mm increments. Knee pain severity is indicated by drawing a vertical mark at the point on the line that best represents the severity of pain. No pain is indicated by the 0 at the far left, and the worst possible pain is indicated by the 100 at the far right.

2. Stiffness Measured With WOMAC Subscale Stiffness Questionnaire at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC Stiffness subscale consisted of two questions scored from 0 to 4. The Stiffness has a range of 0(no stiffness) to 8 (maximal stiffness)

3. Function on Daily Living Measured With WOMAC Subscale Questionnaire Physical Functioning at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC Physical Functioning subscale consisted of seventeen questions scored from 0 to 4. The Physical Functioning has a range of 0 (no functional limitation) to 68 (maximal functional limitation)

4. Pain as Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Pain at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.

5. Symptoms Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Symptoms at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.

6. Function in Daily Living Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Function in Daily Living at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.

7. Sports and Recreational (Sport/Rec) Activities Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Sport/Rec at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.

8. Quality of Life Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Quality of Life Questionnaire at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months [12 months]

   The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.

9. Physical Functioning Measured With Short Form-36 (SF-36) Subscale Physical Functioning Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

   The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. Eight subscales of the Short Form-36 questionnaire are used to derive Physical Component and Mental Component measures

10. Mental Health Measured With Short Form-36 (SF-36) Subscale Mental Health Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

11. Role Physical Measured With Short Form-36 (SF-36) Subscale Role Physical Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

12. Bodily Pain Measured With Short Form-36 (SF-36) Subscale Bodily Pain Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

13. General Health Measured With Short Form-36 (SF-36) Subscale General Health Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

14. Vitality Measured With Short Form-36 (SF-36) Subscale Vitality Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

15. Social Functioning Measured With Short Form-36 (SF-36) Subscale Social Functioning Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

16. Role Emotional Measured With Short Form-36 (SF-36) Subscale Role Emotional Questionnaire at Day 1, 6 Months and 12 Months [12 Months]

    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥40 years and ≤75 years.

• Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.

• Diagnosis of knee osteoarthritis (OA) Grade 2 or 3 according to the Kellgren-Lawrence scale

• Body mass index (BMI) ≤ 40.

• Failed at least 1 conservative OA therapy

• Signed an independent ethics committee (IEC) approved informed consent form (ICF).

Main Exclusion Criteria:

• Intra-articular Hyaluronic (HA) injection within 6 months- On Day 1 (pre-injection), presence of active infection or abnormal effusion in the knee as noted by a physical examination (e.g., erythema, redness, heat, swelling).

• Presence of symptomatic OA in the non-study knee.

• Diagnosed with rheumatoid arthritis (RA), Reiter's syndrome, psoriatic arthritis, ankylosing spondylitis, chondromalacia, arthritis secondary to other inflammatory diseases (e.g., inflammatory bowel disease [IBD], sarcoidosis, or amyloidosis) or of metabolic origin.

• Diagnosis of isolated patella-femoral joint osteoarthritis.

• Valgus/varus deformity judged by the investigator to be clinically significant.

• Disease of spine, hip or other lower extremity joints of sufficient degree to affect assessment of the signal knee. Patients with TKR at the contra-lateral knee or THR in either hip may be enrolled provided sufficient pain relief after TKR or THR which does not require additional analgesic relief.

• Untreated acute traumatic injury of the index knee.

• Presence of a symptomatic meniscal tear in the index knee

• Limited daily activity for reasons other than OA.

• Presence of surgical hardware or other foreign body in the index knee.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krems Hospital	Krems		Austria
2	Monica Hospitals	Antwerp		Belgium
3	Rizzoli Orthopaedic Institute	Bologna		Italy
4	Oslo University	Oslo		Norway

Sponsors and Collaborators

• Zimmer Biomet

Investigators

• Principal Investigator: DiMartino, MD, Bologna (Italy)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zimmer Biomet
• ClinicalTrials.gov Identifier: NCT02138890
• Other Study ID Numbers: BBI.CR.APS1.14
• First Posted: May 15, 2014
• Last Update Posted: Feb 5, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zimmer Biomet: Autologous Protein Solution; APS; Osteoarthritis; Intra Articular Injection
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Recruitment Details	Multicenter study, with 4 centers in Belgium, Italy, Austria and Norway. The first subject was enrolled on 8 May 2014.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution APS: Intra-articular Injection	Saline: Intra-articular injection
Period Title: Overall Study
STARTED	31	15
COMPLETED	30	15
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	APS Injection	Control	Total
Arm/Group Description	Autologous Protein Solution (APS): Intra-articular Injection	Saline: Intra-articular injection	Total of all reporting groups
Overall Participants	31	15	46
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	57.4	54.1	55.8
Sex: Female, Male (Count of Participants)
Female	13 41.9%	6 40%	19 41.3%
Male	18 58.1%	9 60%	27 58.7%
Region of Enrollment (participants) [Number]
Belgium	5 16.1%	3 20%	8 17.4%
Norway	14 45.2%	6 40%	20 43.5%
Italy	12 38.7%	6 40%	18 39.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 6 Months in Pain Measured With WOMAC Questionnaire (Day 1, Week 2, Month 1, 3 and 6)
Description	The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC pain subscale consisted of five questions scored from 0 to 4. The pain has a range of 0 (no pain) to 20 (maximal pain).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety/ITT population analysis population was utilized for this analysis.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	31	15
Day 1	11.5 (2.4)	11.8 (1.9)
Week 2	8.6 (4.0)	8.7 (4.1)
1 Months	7.0 (4.1)	8.4 (3.4)
3 Months	5.6 (3.9)	5.7 (4.2)
6 Months	5.0 (3.8)	5.6 (4.1)

2. Primary Outcome

Title	Pain Measured With WOMAC Questionnaire Subscale Pain at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months.
Description	The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC pain subscale consisted of five questions scored from 0 to 4. The pain has a range of 0 (no pain) to 20 (maximal pain).
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

This data describes mITT/PP analysis set

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution APS: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	11.5 (2.4)	11.8 (1.9)
Week 2	8.6 (4.0)	8.7 (4.1)
1 Month	7.0 (4.1)	8.4 (3.4)
3 Months	5.6 (3.9)	5.7 (4.2)
6 Months	5.0 (3.8)	5.6 (4.1)
12 Months	4.3 (4.0)	6.3 (3.9)

3. Secondary Outcome

Title	Pain Measured With Visual Analogue Scale at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The Visual Analogue Scale is a common tool for measuring general pain. A 100 mm line is marked from 0 to 10 in 10 mm increments. Knee pain severity is indicated by drawing a vertical mark at the point on the line that best represents the severity of pain. No pain is indicated by the 0 at the far left, and the worst possible pain is indicated by the 100 at the far right.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	5.5 (2.2)	6.5 (1.8)
Week 2	4.7 (2.6)	5.3 (2.0)
1 Month	4.0 (2.3)	5.2 (2.1)
3 Months	3.3 (2.0)	3.9 (2.1)
6 Months	3.1 (2.5)	4.1 (2.3)
12 Months	2.6 (2.5)	4.8 (2.2)

4. Secondary Outcome

Title	Stiffness Measured With WOMAC Subscale Stiffness Questionnaire at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC Stiffness subscale consisted of two questions scored from 0 to 4. The Stiffness has a range of 0(no stiffness) to 8 (maximal stiffness)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution APS: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	4.8 (1.7)	5.0 (1.2)
Week 2	4.0 (2.0)	3.6 (1.6)
1 Month	3.3 (1.8)	3.9 (1.3)
3 Months	3.0 (1.6)	3.4 (1.5)
6 Months	2.7 (2.0)	2.9 (1.6)
Month 12	2.7 (1.7)	3.0 (2.0)

5. Secondary Outcome

Title	Function on Daily Living Measured With WOMAC Subscale Questionnaire Physical Functioning at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The WOMAC LK 3.1 questionnaire is a validated tool commonly used for assessing knee pain, stiffness, and function. The WOMAC LK 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item is answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). A higher score indicates worse pain, stiffness, or functional limitation. The WOMAC Physical Functioning subscale consisted of seventeen questions scored from 0 to 4. The Physical Functioning has a range of 0 (no functional limitation) to 68 (maximal functional limitation)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	34.9 (12.4)	38.1 (9.3)
Week 2	30.2 (14.8)	29.4 (15.1)
1 Month	24.9 (14.7)	28.9 (10.8)
3 Months	21.5 (14.5)	20.4 (13.4)
6 Months	18.5 (13.0)	18.0 (12.7)
Month 12	15.6 (13.8)	20.4 (12.3)

6. Secondary Outcome

Title	Pain as Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Pain at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	39.9 (13.1)	37.9 (10.1)
Week 2	51.1 (19.7)	48.0 (16.6)
1 Month	58.2 (19.5)	51.8 (16.3)
3 Months	64.1 (20.7)	64.7 (20.8)
6 Months	66.6 (20.3)	65.9 (19.2)
Month 12	70.6 (21.5)	61.1 (18.5)

7. Secondary Outcome

Title	Symptoms Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Symptoms at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	47.8 (19.3)	46.4 (12.1)
2 Weeks	55.4 (22.0)	54.9 (17.1)
1 Month	64.2 (20.4)	56.1 (15.3)
3 Months	65.3 (17.4)	62.5 (14.6)
6 Months	67.2 (20.3)	63.3 (15.1)
Month 12	68.4 (21.4)	58.2 (17.4)

8. Secondary Outcome

Title	Function in Daily Living Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Function in Daily Living at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	48.6 (18.3)	44.0 (13.7)
Week 2	55.5 (21.8)	56.8 (22.2)
1 Month	63.4 (21.6)	57.5 (15.9)
3 Months	68.3 (21.3)	70.0 (19.8)
6 Months	72.8 (19.1)	73.5 (18.7)
Month 12	77.0 (20.3)	70.0 (18.1)

9. Secondary Outcome

Title	Sports and Recreational (Sport/Rec) Activities Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Sport/Rec at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	23.1 (25)	14.3 (9.4)
Week 2	29.0 (22.4)	23.2 (15.3)
1 Month	30.7 (27.6)	26.6 (18.8)
3 Months	37.7 (27.1)	40.2 (25.1)
6 Months	39.1 (25.3)	42.1 (23.7)
Month 12	47.1 (29.5)	37.1 (27.9)

10. Secondary Outcome

Title	Quality of Life Measured With Knee Injury and Osteoarthritis Outcome Score (KOOS) Subscale Quality of Life Questionnaire at Day 1, Week 2, 1 Month, 3 Months, 6 Months and 12 Months
Description	The KOOS questionnaire is a commonly used instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QOL) (4 questions). The previous week is used as the time period for answering the questions. A higher score on the KOOS questionnaire indicates no problems, and 0 indicates extreme problems. Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). on). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	26.5 (13.8)	22.3 (8.7)
Week 2	29.0 (22.4)	23.2 (15.3)
1 Month	30.7 (27.6)	26.8 (18.8)
3 Months	37.7 (27.1)	40.2 (25.1)
6 Months	39.1 (25.3)	42.1 (23.7)
Month 12	51.3 (25.3)	38.4 (19.3)

11. Secondary Outcome

Title	Physical Functioning Measured With Short Form-36 (SF-36) Subscale Physical Functioning Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. Eight subscales of the Short Form-36 questionnaire are used to derive Physical Component and Mental Component measures
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	35.8 (10.0)	33.9 (9.4)
6 Months	43.3 (9.2)	42.0 (9.6)
Month 12	43.5 (10.2)	42.2 (10.2)

12. Secondary Outcome

Title	Mental Health Measured With Short Form-36 (SF-36) Subscale Mental Health Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	51.5 (8.5)	50.8 (8.9)
Month 6	54.1 (7.7)	53.8 (6.0)
Month 12	55.2 (7.4)	53.0 (7.9)

13. Secondary Outcome

Title	Role Physical Measured With Short Form-36 (SF-36) Subscale Role Physical Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	38.5 (12.0)	38.8 (10.4)
Month 6	44.1 (12.4)	45.7 (11.1)
Month 12	46.0 (10.9)	42.4 (9.3)

14. Secondary Outcome

Title	Bodily Pain Measured With Short Form-36 (SF-36) Subscale Bodily Pain Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	36.7 (7.6)	35.0 (7.9)
Month 6	44.0 (10.9)	43.7 (7.2)
Month 12	47.0 (9.3)	39.2 (7.0)

15. Secondary Outcome

Title	General Health Measured With Short Form-36 (SF-36) Subscale General Health Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	36.7 (7.6)	35.0 (7.9)
Month 6	44.0 (10.9)	43.7 (7.2)
Month 12	47.0 (9.3)	39.2 (7.0)

16. Secondary Outcome

Title	Vitality Measured With Short Form-36 (SF-36) Subscale Vitality Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	51.7 (9.9)	50.6 (7.6)
Month 6	54.0 (8.8)	52.4 (6.5)
Month 12	54.6 (9.9)	53.1 (6.2)

17. Secondary Outcome

Title	Social Functioning Measured With Short Form-36 (SF-36) Subscale Social Functioning Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	43.7 (10.9)	44.5 (10.8)
Month 6	49.6 (9.7)	51.4 (7.4)
Month 12	51.5 (8.3)	47.6 (9.7)

18. Secondary Outcome

Title	Role Emotional Measured With Short Form-36 (SF-36) Subscale Role Emotional Questionnaire at Day 1, 6 Months and 12 Months
Description	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

The 12 Month efficacy analyses were done on the mITT/PP analysis set.

Arm/Group Title	APS Injection	Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection	Saline: Intra-articular injection
Measure Participants	29	14
Day 1	44.0 (13.7)	39.5 (13.5)
Month 6	48.1 (10.7)	47.5 (10.4)
Month 12	49.6 (10.5)	42.5 (9.8)

Adverse Events

Time Frame	Day 1, week 2, month 1, month 3, month 6 and month 12
Adverse Event Reporting Description	Adverse Event reporting through 12-Month time point
Arm/Group Title	APS Injection		Control
Arm/Group Description	Autologous Protein Solution: Intra-articular Injection		Saline: Intra-articular injection
All Cause Mortality
	APS Injection		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/15 (0%)
Serious Adverse Events
	APS Injection		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		1/15 (6.7%)
Injury, poisoning and procedural complications
Meniscus Injury	0/31 (0%)	0	1/15 (6.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/31 (3.2%)	1	0/15 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/31 (3.2%)	1	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	APS Injection		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/31 (45.2%)		6/15 (40%)
Gastrointestinal disorders
Toothache	2/31 (6.5%)	4	0/15 (0%)	0
General disorders
Pain	1/31 (3.2%)	2	0/15 (0%)	0
pyrexia	0/31 (0%)	0	1/15 (6.7%)	1
influenza like ilness	1/31 (3.2%)	1	0/15 (0%)	0
Hepatobiliary disorders
cholelithiasis	1/31 (3.2%)	1	0/15 (0%)	0
Immune system disorders
hypersensitivity	1/31 (3.2%)	1	0/15 (0%)	0
Infections and infestations
Influenza	2/31 (6.5%)	2	0/15 (0%)	0
Upper respiratory tract infection	1/31 (3.2%)	1	0/15 (0%)	0
Tooth abscess	0/31 (0%)	0	1/15 (6.7%)	1
Nasopharyngitis	1/31 (3.2%)	1	0/15 (0%)	0
Gastrointestinal infection	1/31 (3.2%)	1	0/15 (0%)	0
Bronchitis	0/31 (0%)	0	1/15 (6.7%)	1
Urinary tract infection	1/31 (3.2%)	1	0/15 (0%)	0
Injury, poisoning and procedural complications
Meniscus injury	0/31 (0%)	0	1/15 (6.7%)	1
Foot fracture	0/31 (0%)	0	1/15 (6.7%)	1
Ligament Injury	1/31 (3.2%)	1	0/15 (0%)	0
Metabolism and nutrition disorders
Vitamine D Deficiency	1/31 (3.2%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	5/31 (16.1%)	6	3/15 (20%)	7
Back pain	5/31 (16.1%)	8	1/15 (6.7%)	1
Joint crepitation	1/31 (3.2%)	1	0/15 (0%)	0
Joint effusion	0/31 (0%)	0	1/15 (6.7%)	1
Joint swelling	1/31 (3.2%)	1	0/15 (0%)	0
Joint warmth	1/31 (3.2%)	1	0/15 (0%)	0
Muscoskeletal Pain	0/31 (0%)	0	1/15 (6.7%)	1
Neck pain	2/31 (6.5%)	2	0/15 (0%)	0
Osteoarthritis	2/31 (6.5%)	2	0/15 (0%)	0
Rheumatic disorder	1/31 (3.2%)	1	0/15 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/31 (3.2%)	1	0/15 (0%)	0
Nervous system disorders
Headache	4/31 (12.9%)	4	1/15 (6.7%)	1
Psychiatric disorders
Alcoholic hangover	1/31 (3.2%)	1	0/15 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/31 (3.2%)	1	0/15 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/31 (0%)	0	1/15 (6.7%)	1
Vascular disorders
Hypertension	2/31 (6.5%)	2	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.