A Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee (BESPOKE)

: A Randomised, Double-blind, Placebo-controlled, Dose-response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee:

This is a Phase 2b randomised, double-blind, placebo-controlled, dose-response study in subjects with painful osteoarthritis (OA) of the knee. The study will assess the safety and efficacy of multiple doses of MEDI7352 compared to placebo, as well as the pharmacokinetics, pharmacodynamics and immunogenicity of MEDI7352 in subjects with moderate to severe chronic pain persistent for 3 months or more not adequately controlled by standard of care treatments.

Study Overview

• Status: Completed
• Conditions: Painful Osteoarthritis of the Knee
• Intervention / Treatment: Biological: MEDI7352; Biological: MEDI7352; Biological: MEDI7352; Biological: MEDI7352; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 2000
    • Research Site
• Estonia
  • Tallinn, Estonia, 10117
    • Research Site
  • Tartu, Estonia, 50708
    • Research Site
• Germany
  • Bad Doberan, Germany, 18209
    • Research Site
  • Leipzig, Germany, 04107
    • Research Site
  • Munich, Germany, 80809
    • Research Site
• Poland
  • Bialystok, Poland, 15-897
    • Research Site
  • Białystok, Poland, 15-351
    • Research Site
  • Bydgoszcz, Poland, 85-065
    • Research Site
  • Elblag, Poland, 82-300
    • Research Site
  • Gdynia, Poland, 81-338
    • Research Site
  • Lodz, Poland, 90-302
    • Research Site
  • Lublin, Poland, 20-607
    • Research Site
  • Poznan, Poland, 61-113
    • Research Site
  • Puławy, Poland, 24-100
    • Research Site
  • Staszów, Poland, 28-200
    • Research Site
  • Toruń, Poland, 87-100
    • Research Site
  • Warszawa, Poland, 00-874
    • Research Site
  • Zamosc, Poland, 22-400
    • Research Site
• South Africa
  • Bellville, South Africa, 7530
    • Research Site
  • Pinelands, South Africa, 7405
    • Research Site
  • Pretoria, South Africa, 2
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • La Coruña, Spain, 15006
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Malaga, Spain, 29010
    • Research Site
  • Sabadell, Spain, 08208
    • Research Site
  • Santiago De Compostela-Coruña, Spain, 15706
    • Research Site
  • Santiago de Compostela, Spain, 15702
    • Research Site
  • Santiago de Compostela, Spain, 15705
    • Research Site
  • Valencia, Spain, 46010
    • Research Site
• United Kingdom
  • Corby, United Kingdom, NN18 9EZ
    • Research Site
  • Enfield, United Kingdom, EN3 4GS
    • Research Site
  • Glasgow, United Kingdom, G51 4TF
    • Research Site
  • High Wycombe, United Kingdom, HP11 2QW
    • Research Site
  • Leeds, United Kingdom, LS7 4SA
    • Research Site
  • London, United Kingdom, EC2Y 8EA
    • Research Site
  • Northwich, United Kingdom, CW9 7LS
    • Research Site
  • Northwood, United Kingdom, HA6 2RN
    • Research Site
  • Orpington, United Kingdom, BR5 3QG
    • Research Site
  • Preston, United Kingdom, PR2 9QB
    • Research Site
  • Rochdale, United Kingdom, OL11 4AU
    • Research Site
  • Salford, United Kingdom, M6 8HD
    • Research Site
  • Shipley, United Kingdom, BD18 3SA
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must understand the nature of the study and must give signed and dated written informed consent prior to the initiation of any study procedures, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. For participants participating in the optional genetic research, a separate signed and dated optional genetic research ICF must be provided prior to collection of samples for optional genetic research that supports the Genomics Initiative. If a participant declines to participate in the genetic research, this will have no influence on the ability of a participant to participate in the study.
3. The participant should be willing and able to understand and comply with all protocol-specified restrictions and procedures and be able to use an electronic patient-reported outcome (ePRO) device as judged by the investigator.
4. The participant must be considered likely to comply with the study protocol and to have a high probability of completing the study, as judged by the investigator.
5. The participant must be willing and able to discontinue all analgesic therapy with NSAID or COX-2 inhibitors from the start of the washout period until the end of the FU period. This includes over-the-counter (OTC) pain medications and topical analgesics that contain an NSAID or COX-2 inhibitor.

Exclusion Criteria:

1. Requires current treatment with another biologic therapeutic agent, DMARD, or other Immunosuppressants.
2. Previously received any form of anti-NGF; received anti-TNFs including but not limited to golimumab, certolizumab, infliximab, adalimumab, etanercept, or rituximab within 12 months prior to screening, or other biological DMARDs (including but not limited to abatacept, tocilizumab, and tofacitinib), or other immunosuppressants within 6 months prior to screening (with the exception of inhaled or topical corticosteroids).
3. Currently receiving strong opioids for any indication
4. Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening
5. Plasma donation within 28 days of screening or any blood donation or blood loss > 500 mL within 2 months of screening.
6. Previous allogeneic bone marrow or stem cell transplant.
7. Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research.
8. Involvement in the planning and/or conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Dose A: MEDI7352 Q2W	Biological: MEDI7352; Dose A: MEDI7352 Q2W; Biological: MEDI7352; Dose B: MEDI7352 Q2W; Biological: MEDI7352; Dose C: MEDI7352 Q2W; Biological: MEDI7352; Dose D: MEDI7352 Q2W
Experimental: Cohort 2; Dose B: MEDI7352 Q2W	Biological: MEDI7352; Dose A: MEDI7352 Q2W; Biological: MEDI7352; Dose B: MEDI7352 Q2W; Biological: MEDI7352; Dose C: MEDI7352 Q2W; Biological: MEDI7352; Dose D: MEDI7352 Q2W
Experimental: Cohort 3; Dose C: MEDI7352 Q2W	Biological: MEDI7352; Dose A: MEDI7352 Q2W; Biological: MEDI7352; Dose B: MEDI7352 Q2W; Biological: MEDI7352; Dose C: MEDI7352 Q2W; Biological: MEDI7352; Dose D: MEDI7352 Q2W
Experimental: Cohort 4; Dose D: MEDI7352 Q2W	Biological: MEDI7352; Dose A: MEDI7352 Q2W; Biological: MEDI7352; Dose B: MEDI7352 Q2W; Biological: MEDI7352; Dose C: MEDI7352 Q2W; Biological: MEDI7352; Dose D: MEDI7352 Q2W
Placebo Comparator: Cohort 5: Placebo to match MEDI7352 Q2W	Biological: Placebo; Placebo to match MEDI7352 Q2W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Rating Scale pain scores	Change in the weekly average of daily NRS pain scores from baseline to Week 12. Average daily pain scores in the target joint will be recorded from a scale of 0 = "no pain" to 10 = "most severe pain imaginable over the previous 24 hours.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale from	Change in the WOMAC pain subscale from baseline to Week 12. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain	12 Weeks
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function	Change in the WOMAC physical function subscale from baseline to Week 12 The WOMAC physical function subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function	12 Weeks
Physician Global Assesment (PGA of OA)	Change in the PGA of OA from baseline to Week 12. The PGA of OA is a 5-point scale used to assess symptoms and activity impairment due to OA of the knee. Participants are asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities).	12 Weeks
ADA titre	Serum concentration of ADA titre	12 weeks
Adverse Events	Number of Participants with adverse events and serious adverse events	Through study completion, an average of 10 months
Anti-drug Antibodies (ADA)	Presence of ADA to MEDI7352	through study completion, an average of 10 months
concentration of MEDI7352	Serum concentration of MEDI7352	through study completion, an average of 10 months
Percentage of responders as measured by the OARSI responder index using the OMERACT-OARSI	Percentage of responders as measured by the OARSI responder index using the OMERACT-OARS (Outcome Measures in Rheumatology Clinical Trials -OMERACT and Osteoarthritis Research Society International OARSI) at Weeks 2, 4, 8, 12, and 18	Weeks 2, 4, 8, 12, and 18
Vital Signs (Blood Pressure) in mmHg	Change from baseline supine and standing blood pressure in all participants	Through study completion, an average of 10 months
Vital Signs (Heart Rate) in beats per minute	Change from baseline heart rate in all participants	Through study completion, an average of 10 months
Vital Signs (Respiratory Rate) in breaths per minute	Change from baseline respiratory rate in all participants	Through study completion, an average of 10 months
Vital Signs (Temperature) in °C	Change from baseline temperature measurements in all participants	Through study completion, an average of 10 months
Clinical laboratory assessments	Number of Participants with abnormal laboratory values	Through study completion, an average of 10 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Osteoarthritis
• Additional Relevant MeSH Terms: Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Pain
• Other Study ID Numbers: D5680C00003; 2020-003797-51 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool.

Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be In place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No