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Efficacy and Safety Trial of PTP-001 (MOTYS) for Symptomatic Knee Osteoarthritis

18 juillet 2022 mis à jour par: Bioventus LLC

A Multiple Arm, Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase 2 Study of Intra-Articular Administration of an Allogeneic Human Placental Tissue Particulate (PTP-001) for the Treatment of Knee Osteoarthritis

Evaluation of safety, tolerability and efficacy of a single intra-articular (IA) injection of PTP-001, an allogeneic placental tissue particulate, in individuals with knee osteoarthritis (OA).

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Description détaillée

This is a multiple arm, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-arm, phase 2 study of intra-articular administration of an allogeneic human placental tissue particulate (PTP-001) for the treatment of knee osteoarthritis. The study is planned to be conducted outside the United States. A total of approximately 210 participants are planned to be randomized to receive 1 of 2 doses of PTP-001 (100 mg or 200 mg) or saline vehicle control (placebo) injection. The purpose of the trial is to evaluate the efficacy, safety and tolerability of a single low dose and high dose of PTP-001 compared to placebo over a 26-week period.

Type d'étude

Interventionnel

Inscription (Anticipé)

210

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • New South Wales
      • Botany, New South Wales, Australie, 2019
        • Emeritus Research Sydney
      • Broadmeadow, New South Wales, Australie, 2292
        • Genesis Research Services
      • Saint Leonards, New South Wales, Australie
        • Royal North Shore Hospital
      • Sydney, New South Wales, Australie, 2010
        • Holdsworth House Medical Practice
    • Victoria
      • Camberwell, Victoria, Australie, 3124
        • Emeritus Research Melbourne
      • Quebec, Canada, G1W 4R4
        • Centrede Recherche Saint-Louis
    • Ontario
      • Hamilton, Ontario, Canada, L8M 1K7
        • Hamilton Medical Research Group
      • Hamilton, Ontario, Canada, L8N 4A6
        • McMaster University Department of Surgery St. Joseph's Healthcare Hamilton
      • Toronto, Ontario, Canada, M3J 0K2
        • Canadian Phase Onward Inc.
    • Quebec
      • Québec, Quebec, Canada, G1N4V3
        • Diex Recherche Quebec Inc.
      • Sherbrooke, Quebec, Canada, J1L 0H8
        • DIEX Recherche Sherbrooke Inc.
      • Gandrup, Danemark, 9362
        • Sanos Clinic Nordjylland
      • Herlev, Danemark, 2730
        • Sanos Clinic
      • Vejle, Danemark, 7100
        • Sanos Clinic Syddanmark

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

40 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Participants are eligible to be included in the study only if all of the following criteria apply:

    1. Male or female, aged 40 to 80 years
    2. Symptomatic knee OA with Kellgren-Lawrence radiographic classification of 2 or 3 (mild or moderate) as assessed by the central reading facility
    3. Target knee pain ≥ 20 and ≤ 40 out of 50 the WOMAC®NRS 3.1 pain questionnaire (sum of 5 questions) at screening and baseline
    4. Onset of symptomatic OA of the target knee was at least 6 months prior to screening
    5. Insufficient or failed response or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs, as reported by the participant
    6. IF FEMALE, must meet all of the following:

      • Not breast feeding
      • Not planning to become pregnant during the study
      • If of childbearing potential, must have a negative pregnancy test result within 72 hours prior to receiving the intra-articular injection, and must commit to the use of a highly effective form of birth control (See Appendix A) for at least 12 weeks after the injection
    7. Willingness to remain on the same oral "rescue" (as needed) analgesic as the only pharmacologic treatment for knee pain during the study
    8. Willingness to abstain from taking any illicit or unauthorized medications for treatment of OA or any other concurrent condition during the study
    9. Written informed consent is obtained from the participant

Exclusion Criteria:

  • Participants are excluded from the study if any of the following criteria apply:

    1. Participant is non-ambulatory (unable to walk >50 feet without assistance)
    2. Clinically severe obesity as defined by the National Institutes of Health (body mass target ≥40 kg/m2)
    3. Contralateral knee pain equal to or exceeding the pain in the target knee (on the WOMAC® NRS3.1 pain questionnaire) at screening and/or baseline
    4. Clinically significant effusion of the target knee at either the screening or baseline visits determined by physical examination (e.g., ballotable patella or positive bulge sign). Note: Participants presenting with effusion may be enrolled in the study after undergoing knee aspiration to remove excess fluid in the target joint.
    5. Severe (excessive) malalignment of the tibial-femoral axis, assessed radiographically
    6. Presence of active infection of the target knee or systemic infection requiring treatment within the 3 months prior to screening
    7. Clinical diagnosis of inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, etc.) established by clinical history, examination, or serology
    8. Participant is receiving, has received, or plans to receive any of the following therapies

      • Prior administration of hyaluronic acid, extended release corticosteroid (e.g., Zilretta®), platelet-rich plasma (PRP), or stem cell therapies by intra-articular injection(s) of the target knee within 6 months prior to screening
      • Prior intra-articular corticosteroid within 3 months prior to screening or into any other joint within 30 days prior to screening
      • Current chronic systemic use of corticosteroids in doses exceeding 10 mg prednisolone-equivalents daily
      • Treatment with any investigational therapy (drug, device, or biologic) within 3 months prior to screening or is planned for the duration of the study
      • Treatment with immunosuppressive medication or chemotherapy within the past 5 years
    9. Chronic use of narcotics or alcohol abuse within the past 6 months prior to screening
    10. Surgery to the target knee (including arthroscopy) within 6 months prior to receiving the intra-articular injection or planned surgery to the target knee within 6 months after the injection
    11. Participant previously underwent arthroplasty of the target knee
    12. Presence of joint instability or complaints of locking, intermittent limitation in range of motion, or loose body sensation, suggestive of internal derangement of the knee (either extremity)
    13. Symptomatic OA of the non-target knee that is not responsive to paracetamol (acetaminophen) or oral nonsteroidal anti-inflammatory drugs (NSAIDs).
    14. Diagnosis of lower extremity gout or pseudo-gout in the past 6 months
    15. Osteonecrosis of either knee
    16. Significant acute (within the past 3 months) injury to the target knee
    17. History of receiving a solid organ or hematologic transplant
    18. History of malignancy, radiotherapy, or chemotherapy for malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin
    19. History of prior radiation therapy of the target knee
    20. History of autoimmune disease affecting the musculoskeletal system
    21. Known (documented) history of acquired immune deficiency syndrome or human immunodeficiency virus
    22. Any condition causing pain in or around the target knee (e.g., radiating pain, pain in another region of the ipsilateral lower extremity) that may interfere with assessment(s) of the target knee
    23. Other chronic pain anywhere in the body that requires the chronic use of analgesic medications, such as fibromyalgia, neuropathic pain, low back pain, etc.
    24. Presence of contraindications for use of 3 g/day of orally administered paracetamol/acetaminophen due to known hypersensitivity or hepatic impairment.
    25. Known presence of any concurrent medical condition (e.g., hematologic renal, hepatic, cardiac, or coagulation abnormalities) that in the investigator's judgment would interfere with the required study assessments and study participation
    26. Participant is involved in litigation (e.g., worker's compensation) for a medical condition or injury at any anatomical site

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: PTP-001 200 mg
A single intra-articular injection in the target knee of PTP-001 200 mg.
Allogeneic human placental tissue particulate (PTP-001) is administered as a single intra-articular injection to the target knee after resuspension with saline.
Expérimental: PTP-001 100 mg
A single intra-articular injection in the target knee of PTP-001 100 mg.
Allogeneic human placental tissue particulate (PTP-001) is administered as a single intra-articular injection to the target knee after resuspension with saline.
Comparateur placebo: Placebo/saline
A single intra-articular injection in the target knee of 4mL of placebo control - physiological saline (0.9% sodium chloride injection, USP).
The placebo control, physiological saline (0.9% sodium chloride injection, USP), is administered as an intra-articular injection to the target knee.
Autres noms:
  • Sérum physiologique

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Efficacy - Change from pretreatment baseline in the WOMAC pain subscale
Délai: At 6 months
To evaluate the change from pretreatment baseline in the WOMAC pain sub-score in the target knee on an 11-box numerical rating scale, with categories from 0 (none) to 10 (extreme), normalized on scales of 0-100.
At 6 months
Safety - Incidence of local and systemic AEs
Délai: Over 6 months
To assess the long-term (6 months) incidence of local and systemic AEs, and consists of physical examination, laboratory values, AEs, AESI, and immunogenicity testing.
Over 6 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change from pretreatment baseline in pain intensity assessed by participant self report (WOMAC Pain subscale).
Délai: At 2 weeks, 3 months, 4 months, 5 months.
WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) is measured on an 11-box numerical rating scale, with categories from 0 (none) to 10 (extreme), normalized to a scale of 0-100, where higher score represents higher pain.
At 2 weeks, 3 months, 4 months, 5 months.
Change from pretreatment baseline in function assessed by participant self-report (WOMAC Function subscale).
Délai: At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC C (measure of physical function) is measured on 11-point NRS ranging from 0 (none) to 10 (extreme), where higher score represents higher difficulties in physical function.
At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
Change from pretreatment baseline in the weekly average of daily pain assessed by patient self report (NRS).
Délai: At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
The question is an average daily (24-h) pain intensity score on a 0 to 10 NRS scale with 0 indicating 'no pain' and 10 indicating 'pain as bad as you can imagine'.
At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
Change from pretreatment baseline in patient global assessment of OA (PGA-OA) assessed by participant self report.
Délai: At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
Considering all the ways knee osteoarthritis affects the participants, the question is an average daily (24-h) self-reported global assessment on an 11-box numerical rating scale, with 0 indicating "very good" and 10 indicating "very poor".
At 2 weeks, 3 months, 4 months, 5 months, and 6 months.
Change from pretreatment baseline in participant self-reported quality of life measured by SF-36 overall score, PCS, and MCS.
Délai: At 3 months and 6 months.

The SF-36 measures 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health, and has 2 summary scores (physical and mental). The physical health measure includes 4 scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items).

The assessment is performed on a scale of 0 (maximum disability)-100 (no disability) with higher scores indicating better health status.

At 3 months and 6 months.
Response to PTP-001 on the OMERACT-OARSI responder criteria.
Délai: At 2 weeks, 3 months, and 6 months.
The OMERACT-OARSI responder criteria involve changes that are deemed to be clinically relevant in the three domains: pain, function, and Patient Global Assessment. For each of these domains, ranges are defined for absolute and percent changes from baseline that correspond to "high improvement" and "moderate improvement". OMERACT-OARSI response is defined as either i) improvement in pain or physical function ≥50% and an absolute change ≥20 mm on a 100-mm visual analog scale; or (2) improvement of ≥20% and with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment (PGA).
At 2 weeks, 3 months, and 6 months.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Collaborateurs

Les enquêteurs

  • Chercheur principal: Moin Khan, MD, McMaster University Department of Surgery St. Joseph's Healthcare Hamilton

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

30 septembre 2021

Achèvement primaire (Anticipé)

31 octobre 2022

Achèvement de l'étude (Anticipé)

30 novembre 2022

Dates d'inscription aux études

Première soumission

19 octobre 2021

Première soumission répondant aux critères de contrôle qualité

19 octobre 2021

Première publication (Réel)

29 octobre 2021

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

19 juillet 2022

Dernière mise à jour soumise répondant aux critères de contrôle qualité

18 juillet 2022

Dernière vérification

1 juillet 2022

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • KOA-21-02

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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