pAF for the Treatment of Osteoarthritis

NCT04886960 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 128491
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis

Conditions

Osteo Arthritis Knee

Keywords

Amniotic Fluid; Osteo Arthritis

Outcome Measures

Primary Outcomes (1)

• Repeat Allogeneic Intra-articular Injection Within 6 Months.

  Participants in both the SOC and pAF treatment arms may require and/or request rescue medication (i.e. SOC injection) at any time and will be given per PI discretion as part of standard of care. The clinicians will not know which study arm the study participant is in but will treat the participant with the SOC injection. This information will be documented and collected in the Electronic Medical Record (EMR), as well as the study's electronic data capture system. Participants will not be given any additional pAF injections throughout the study period. The participant will continue to be treated with SOC injections as needed. The outcome will be an indicator of whether or not a subject received a rescue medication within 6 months.

  6 months

Secondary Outcomes (4)

• Knee Injury and Osteoarthritis Outcome Score (KOOS)

  6 months

• Visual Analog Scale for Pain (VAS Pain)

  6 months

• Single Assessment Numerical Evaluation (SANE)

  6 months

• Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT)

  6 months

Other Outcomes (1)

• Number of Treatment Emergent Adverse Events (AEs) Directly Related to the Injection.

  1 day, 2 days, 1 month, 3 months, 6 months, 12 months

Study Arms (2)

Amniotic Fluid Injection

EXPERIMENTAL

Amniotic Fluid Injection, 3ml, one time dose.

Biological: Amniotic Fluid Injection

Standard of Care Steroid Injection

ACTIVE COMPARATOR

Corticosteroids, 3ml, one time dose.

Other: Standard of Care

Interventions

Amniotic Fluid Injection BIOLOGICAL

Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis

Also known as: Processed Amniotic Fluid, pAF, Human Amniotic Fluid, hAF

Amniotic Fluid Injection

Standard of Care OTHER

Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis

Also known as: Corticosteriods 3ml, one time dose

Standard of Care Steroid Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are between the ages of 18-70 years
• A confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings consistent with Kellgren-Lawrence Stage 2-3 disease
• Patients who have failed conservative treatment (e.g. steroid, activity modification, therapy, etc.) within 3 months
• Unilateral or bilateral chronic knee joint pain \>4 months
• Patients who are able to ambulate (i.e. not wheelchair bound)
• Patient reported a typical pain of at least 4 out of 10 during the past week using VAS numeric pain scale (0-10)
• Patients who are of childbearing potential must agree to use adequate contraception for 90 days after study drug injection

You may not qualify if:

• Subjects who have had a previous injection (i.e. steroid, platelet rich plasma, or other) within the last 3 months
• A focal chondral defect, defined by x-ray evaluation
• BMI \>40 as defined by NIH Clinical Guidelines Body Mass Index
• Concurrent participation in another investigational trial involving systemic administration of agents (within the previous 30 days) or plans to participate in any other allogeneic stem cell therapy trial during the 12 month follow-up period
• Clinical suspicion of infection at injection site
• Any surgeries within 4 weeks, other than diagnostic surgery
• Insulin or self-reported non-insulin dependent diabetic evident of HgA1c ≥8% among known diabetics
• Unable to consent to an English Language Consent Form
• Frank mechanical issues (i.e. locking of the knee)
• Workman's Compensation cases
• Rheumatoid arthritis
• Patients with a known allergy to local anesthetics or components of the study drug (pAF or steroid injection)
• Patients with vascular claudication or neurologic disorders affecting the index lower limb
• Patients with inflammatory arthropathies or connective tissue disorders; or
• Patients with known alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or have used medical marijuana within 7 days of study enrollment

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah Orthopedic Center

Salt Lake City, Utah, 84108, United States

Location

Related Publications (19)

• Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum. 2009 Dec;60(12):3546-53. doi: 10.1002/art.24984.

  PMID: 19950287 BACKGROUND

• Underwood MA, Gilbert WM, Sherman MP. Amniotic fluid: not just fetal urine anymore. J Perinatol. 2005 May;25(5):341-8. doi: 10.1038/sj.jp.7211290.

  PMID: 15861199 BACKGROUND

• Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschlager M. Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? Hum Reprod. 2003 Jul;18(7):1489-93. doi: 10.1093/humrep/deg279.

  PMID: 12832377 BACKGROUND

• Bottai D, Cigognini D, Nicora E, Moro M, Grimoldi MG, Adami R, Abrignani S, Marconi AM, Di Giulio AM, Gorio A. Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations. Restor Neurol Neurosci. 2012;30(1):55-68. doi: 10.3233/RNN-2011-0620.

  PMID: 22377907 BACKGROUND

• Johnson, H.L., Peritoneal Immunization. The American Journal of Surgery, 1936. 34(2): p. 266-271

  BACKGROUND

• Shimberg, M., The Use of Amniotic Fluid Concentrate in Orthopedic Conditions. The Journal of Bone and Joint Surgery, 1938(20): p. 167-177

  BACKGROUND

• Ismail MA, Salti GI, Moawad AH. Effect of amniotic fluid on bacterial recovery and growth: clinical implications. Obstet Gynecol Surv. 1989 Aug;44(8):571-7. doi: 10.1097/00006254-198908000-00001. No abstract available.

  PMID: 2668811 BACKGROUND

• Ojo VA, Okpere EE, Obaseiki-Ebor EE. Antimicrobial properties of amniotic fluid from some Nigerian women. Int J Gynaecol Obstet. 1986 Apr;24(2):97-101. doi: 10.1016/0020-7292(86)90002-0.

  PMID: 2874087 BACKGROUND

• Siggers J, Ostergaard MV, Siggers RH, Skovgaard K, Molbak L, Thymann T, Schmidt M, Moller HK, Purup S, Fink LN, Frokiaer H, Boye M, Sangild PT, Bering SB. Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates. Am J Physiol Gastrointest Liver Physiol. 2013 May 15;304(10):G864-75. doi: 10.1152/ajpgi.00278.2012. Epub 2013 Mar 21.

  PMID: 23518680 BACKGROUND

• Ozgenel GY, Filiz G, Ozcan M. Effects of human amniotic fluid on cartilage regeneration from free perichondrial grafts in rabbits. Br J Plast Surg. 2004 Jul;57(5):423-8. doi: 10.1016/j.bjps.2003.12.021.

  PMID: 15191823 BACKGROUND

• Ozgenel GY, Filiz G. Combined application of human amniotic membrane wrapping and hyaluronic acid injection in epineurectomized rat sciatic nerve. J Reconstr Microsurg. 2004 Feb;20(2):153-7. doi: 10.1055/s-2004-820772.

  PMID: 15011124 BACKGROUND

• Karacal N, Kosucu P, Cobanglu U, Kutlu N. Effect of human amniotic fluid on bone healing. J Surg Res. 2005 Dec;129(2):283-7. doi: 10.1016/j.jss.2005.03.026.

  PMID: 15916770 BACKGROUND

• Castro-Combs J, Noguera G, Cano M, Yew M, Gehlbach PL, Palmer J, Behrens A. Corneal wound healing is modulated by topical application of amniotic fluid in an ex vivo organ culture model. Exp Eye Res. 2008 Jul;87(1):56-63. doi: 10.1016/j.exer.2008.04.010. Epub 2008 Apr 30.

  PMID: 18555991 BACKGROUND

• Nyman E, Huss F, Nyman T, Junker J, Kratz G. Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: in vitro studies of re-epithelialisation in human skin wounds. J Plast Surg Hand Surg. 2013 Apr;47(2):89-92. doi: 10.3109/2000656X.2012.733169. Epub 2013 Jan 29.

  PMID: 23356944 BACKGROUND

• Weissenbacher T, Laubender RP, Witkin SS, Gingelmaier A, Schiessl B, Kainer F, Friese K, Jeschke U, Dian D, Karl K. Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid. BMC Res Notes. 2012 Jul 24;5:375. doi: 10.1186/1756-0500-5-375.

  PMID: 22827842 BACKGROUND

• Merimee TJ, Grant M, Tyson JE. Insulin-like growth factors in amniotic fluid. J Clin Endocrinol Metab. 1984 Oct;59(4):752-5. doi: 10.1210/jcem-59-4-752.

  PMID: 6384254 BACKGROUND

• Hung M, Bounsanga J, Voss MW, Saltzman CL. Establishing minimum clinically important difference values for the Patient-Reported Outcomes Measurement Information System Physical Function, hip disability and osteoarthritis outcome score for joint reconstruction, and knee injury and osteoarthritis outcome score for joint reconstruction in orthopaedics. World J Orthop. 2018 Mar 18;9(3):41-49. doi: 10.5312/wjo.v9.i3.41. eCollection 2018 Mar 18.

  PMID: 29564213 BACKGROUND

• Winterstein AP, McGuine TA, Carr KE, Hetzel SJ. Comparison of IKDC and SANE Outcome Measures Following Knee Injury in Active Female Patients. Sports Health. 2013 Nov;5(6):523-9. doi: 10.1177/1941738113499300.

  PMID: 24427427 BACKGROUND

• Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003 May 25;1:17. doi: 10.1186/1477-7525-1-17.

  PMID: 12801417 BACKGROUND

MeSH Terms

Interventions

Platelet Activating Factor; MICU1 protein, human; Standard of Care

Intervention Hierarchy (Ancestors)

Choline; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds; Phospholipid Ethers; Glycerophospholipids; Phosphatidic Acids; Glycerophosphates; Phospholipids; Membrane Lipids; Lipids; Blood Coagulation Factors; Biological Factors; Autacoids; Inflammation Mediators; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Protocol deviations and participant eligibility were monitored throughout the study. Procedures were in place to document any errors in treatment administration or deviations from eligibility criteria.

Results Point of Contact

• Title: Jamie Egbert, MPH
• Organization: University of Utah Health: Department of Orthopaedics

jamie.egbert@utah.edu

801-587-7109

Study Officials

• David Petron, MD

  University of Utah Orthopaedic Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Half of the patients will be in the SOC treatment arm and half of the patients will be in the AF arm. The PI and patients will be blinded as to the arm in which they will be participating. Once the randomization number is obtained, unblinded research staff will prepare the appropriate study drug. The injections will be blinded to the research coordinator in charge of data entry, the treating physician and the patient.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 14, 2021
• Study Start: July 8, 2021
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)