The Current Status of Clinical Trials on Biologics for Cartilage Repair and Osteoarthritis Treatment: An Analysis of ClinicalTrials.gov Data

Abstract

Objective: Biologics are increasingly used for cartilage repair and osteoarthritis (OA) treatment. This study aimed to provide an overview of the clinical trials conducted on this subject.

Design: Two-word combinations of two sets of key words "cartilage"; "joint"; "osteoarthritis" and "biologics"; "stem cells"; "cell implantation" were used to search the database of ClinicalTrials.gov and supplemented with searches of PubMed and EMbase. The registered trials were analyzed for clinical conditions, completion status, phases, and investigated biologics. Recently completed trials with posted/published results were summarized.

Results: From 2000 to 2022, a total of 365 clinical trials were registered at ClinicalTrials.gov to use biologics for cartilage repair and OA treatment. Since 2006, the number of registered trials accelerated at an annual rate of 16.4%. Of the 265 trials designated with a phase, 72% were early Phase 1, Phase 1, and Phase 2. Chondrocytes and platelet-rich plasma (PRP) were studied in nearly equal number of early- and late-stage trials. Mesenchymal stem/stromal cells (MSCs) were the most commonly investigated biologics (38%) and mostly derived from bone marrow and adipose tissue (70%). In last 5 years, 32 of the 72 completed trials posted/published results, among which seven Phase 3 trials investigated chondrocytes, PRP, bone marrow aspirate concentrate, hyaluronic acid, collagen membrane, and albumin.

Conclusions: There was a rapid increase in the number of registered clinical trials in recent years, using a variety of biologics for cartilage repair and OA treatment. Majority of the biologics still require late-stage trials to validate their clinical effectiveness.

Keywords: biologics; cartilage; clinical trial; osteoarthritis; registry.

Figure 1.

Analysis of 365 clinical trials on biologics for cartilage repair and osteoarthritis treatment. (A) Distribution of the 365 trials over the years. There are a few trials registered between 2000 and 2005. The annual trial registration is fluctuated but a 5-year moving trend shows stead increase after 2006. (B) Detailed trial phases of the 365 trials in percentages. Early Phase trials, including early Phase 1 trials to Phase 2/3 trials, make up a large collective group (52%), while Advanced trials, including Phases 3 and 4, make up 20% of the 365 trials. (C) The distribution of Early Phase trials vs. Advanced Phase trials over the years. The Early Phase trials increase at a more rapid pace than Advanced Phase trials. (D) The current status of the trials in percentage. (E) The trial status of Early Phase trials vs. Advanced Phase trials. Their statuses are similarly proportionated. 5. per Mov. Avg. = moving average per 5 years; Adv. Phase = Advanced Phase; incomplete = active + not recruiting + recruiting + by invitation; terminated = suspended + terminated + withdrawn.

Figure 2.

(A) The distribution of the 365 clinical trials per joints and medical conditions. A predominant target of the trials is knee OA. Note: Several trials were designed for both osteoarthritis and cartilage defect treatments and performed on multiple joints. (B) Distribution of the 365 clinical trials per types of biologics used. MSCs, PRP, chondrocytes, BMAC and HA are among the most often used biologics in the trials. Bio-molecules include antibodies, antagonists, growth factors and other biologically active major molecules; Amnionic includes products from amnionic tissue/fluid, placental tissue and umbilical cord. OA = osteoarthritis; MSCs = mesenchymal stem/stromal cells; PRP = platelet-rich plasma; BMAC = bone marrow aspirate concentrate; HA = hyaluronic acid; Defect = cartilage defect; TMJ = temporomandibular joint; SVF = adipose tissue stromal vascular fraction; micro-Fat = micro-fragmented fat tissue; Blood-deri. = blood derivatives; Other bio = other biologics.