Back to resultsA Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee (BESPOKE)
Primary Purpose
Painful Osteoarthritis of the Knee
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI7352
MEDI7352
MEDI7352
MEDI7352
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Painful Osteoarthritis of the Knee focused on measuring Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
- 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.
- 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.
- 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:
- Requires current treatment with another biologic therapeutic agent, DMARD, or other Immunosuppressants.
- 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).
- Currently receiving strong opioids for any indication
- Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening
- Plasma donation within 28 days of screening or any blood donation or blood loss > 500 mL within 2 months of screening.
- Previous allogeneic bone marrow or stem cell transplant.
- Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research.
- Involvement in the planning and/or conduct of the study.
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5:
Arm Description
Dose A: MEDI7352 Q2W
Dose B: MEDI7352 Q2W
Dose C: MEDI7352 Q2W
Dose D: MEDI7352 Q2W
Placebo to match MEDI7352 Q2W
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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).
ADA titre
Serum concentration of ADA titre
Adverse Events
Number of Participants with adverse events and serious adverse events
Anti-drug Antibodies (ADA)
Presence of ADA to MEDI7352
concentration of MEDI7352
Serum concentration of MEDI7352
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
Vital Signs (Blood Pressure) in mmHg
Change from baseline supine and standing blood pressure in all participants
Vital Signs (Heart Rate) in beats per minute
Change from baseline heart rate in all participants
Vital Signs (Respiratory Rate) in breaths per minute
Change from baseline respiratory rate in all participants
Vital Signs (Temperature) in °C
Change from baseline temperature measurements in all participants
Clinical laboratory assessments
Number of Participants with abnormal laboratory values
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04675034
Brief Title
A Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee
Acronym
BESPOKE
Official Title
: A Randomised, Double-blind, Placebo-controlled, Dose-response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee:
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 2, 2020 (Actual)
Primary Completion Date
August 16, 2023 (Actual)
Study Completion Date
August 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Osteoarthritis of the Knee
Keywords
Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a Phase IIb, multinational, multicentre, randomised, double-blind, placebo-controlled, dose-response study of MEDI7352 in participants 18 to 80 years of age (inclusive) with moderate-to-severe chronic pain of the knee. The study consists of a screening period of up to 45 days, a 12-week treatment period, and a 24-week follow-up (FU) period.
Daily pain scores (as measured on an 11-point numerical rating scale [NRS]) recorded at the first screening visit and from Day -7 to Day -1 will be used be used to determine eligibility.
Participants will be randomised to one of 4 doses of MEDI7352 or placebo. Each participant will receive 6 doses of MEDI7352 or placebo during the treatment period.
After the end-of-treatment (EOT) visit at Week 12, participants will enter the FU period, which comprises 3 clinic visits (Weeks 18, 32, and 36) and 4 FU phone calls (Weeks 15, 21, 24, and 28). All participants who receive IP are expected to complete the FU period.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All participants will be centrally assigned to randomised IP using an IRT/RTSM system. Before the study is initiated, the telephone number and call-in directions for the IRT and/or the log in information and directions for the RTSM will be provided to each site.
The IRT/RTSM will provide the investigator(s) or appropriate study personnel with the kit identification number to be allocated to the participant at the IP dosing visit.
Details for this will be described in the IRT/RTSM user manual that will be provided to each centre.
All participants, investigators, and study personnel involved in the conduct of the study will be blinded to treatment assignment. The unblinded study personnel (eg, site pharmacist) will not participate in study procedures or data analysis prior to unblinding of the study data to all study-related personnel. Unblinded AstraZeneca personnel who are not otherwise involved in the study will prepare data for review and interim analyses.
Allocation
Randomized
Enrollment
390 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Dose A: MEDI7352 Q2W
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Dose B: MEDI7352 Q2W
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Dose C: MEDI7352 Q2W
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Dose D: MEDI7352 Q2W
Arm Title
Cohort 5:
Arm Type
Placebo Comparator
Arm Description
Placebo to match MEDI7352 Q2W
Intervention Type
Biological
Intervention Name(s)
MEDI7352
Intervention Description
Dose A: MEDI7352 Q2W
Intervention Type
Biological
Intervention Name(s)
MEDI7352
Intervention Description
Dose B: MEDI7352 Q2W
Intervention Type
Biological
Intervention Name(s)
MEDI7352
Intervention Description
Dose C: MEDI7352 Q2W
Intervention Type
Biological
Intervention Name(s)
MEDI7352
Intervention Description
Dose D: MEDI7352 Q2W
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo to match MEDI7352 Q2W
Primary Outcome Measure Information:
Title
Numerical Rating Scale pain scores
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale from
Description
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
Time Frame
12 Weeks
Title
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function
Description
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
Time Frame
12 Weeks
Title
Physician Global Assesment (PGA of OA)
Description
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).
Time Frame
12 Weeks
Title
ADA titre
Description
Serum concentration of ADA titre
Time Frame
12 weeks
Title
Adverse Events
Description
Number of Participants with adverse events and serious adverse events
Time Frame
Through study completion, an average of 10 months
Title
Anti-drug Antibodies (ADA)
Description
Presence of ADA to MEDI7352
Time Frame
through study completion, an average of 10 months
Title
concentration of MEDI7352
Description
Serum concentration of MEDI7352
Time Frame
through study completion, an average of 10 months
Title
Percentage of responders as measured by the OARSI responder index using the OMERACT-OARSI
Description
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
Time Frame
Weeks 2, 4, 8, 12, and 18
Title
Vital Signs (Blood Pressure) in mmHg
Description
Change from baseline supine and standing blood pressure in all participants
Time Frame
Through study completion, an average of 10 months
Title
Vital Signs (Heart Rate) in beats per minute
Description
Change from baseline heart rate in all participants
Time Frame
Through study completion, an average of 10 months
Title
Vital Signs (Respiratory Rate) in breaths per minute
Description
Change from baseline respiratory rate in all participants
Time Frame
Through study completion, an average of 10 months
Title
Vital Signs (Temperature) in °C
Description
Change from baseline temperature measurements in all participants
Time Frame
Through study completion, an average of 10 months
Title
Clinical laboratory assessments
Description
Number of Participants with abnormal laboratory values
Time Frame
Through study completion, an average of 10 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
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.
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.
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:
Requires current treatment with another biologic therapeutic agent, DMARD, or other Immunosuppressants.
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).
Currently receiving strong opioids for any indication
Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening
Plasma donation within 28 days of screening or any blood donation or blood loss > 500 mL within 2 months of screening.
Previous allogeneic bone marrow or stem cell transplant.
Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research.
Involvement in the planning and/or conduct of the study.
Facility Information:
Facility Name
Research Site
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Facility Name
Research Site
City
Tallinn
ZIP/Postal Code
10117
Country
Estonia
Facility Name
Research Site
City
Tartu
ZIP/Postal Code
50708
Country
Estonia
Facility Name
Research Site
City
Bad Doberan
ZIP/Postal Code
18209
Country
Germany
Facility Name
Research Site
City
Leipzig
ZIP/Postal Code
04107
Country
Germany
Facility Name
Research Site
City
Munich
ZIP/Postal Code
80809
Country
Germany
Facility Name
Research Site
City
Bialystok
ZIP/Postal Code
15-897
Country
Poland
Facility Name
Research Site
City
Białystok
ZIP/Postal Code
15-351
Country
Poland
Facility Name
Research Site
City
Bydgoszcz
ZIP/Postal Code
85-065
Country
Poland
Facility Name
Research Site
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Research Site
City
Gdynia
ZIP/Postal Code
81-338
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-302
Country
Poland
Facility Name
Research Site
City
Lublin
ZIP/Postal Code
20-607
Country
Poland
Facility Name
Research Site
City
Poznan
ZIP/Postal Code
61-113
Country
Poland
Facility Name
Research Site
City
Puławy
ZIP/Postal Code
24-100
Country
Poland
Facility Name
Research Site
City
Staszów
ZIP/Postal Code
28-200
Country
Poland
Facility Name
Research Site
City
Toruń
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
00-874
Country
Poland
Facility Name
Research Site
City
Zamosc
ZIP/Postal Code
22-400
Country
Poland
Facility Name
Research Site
City
Bellville
ZIP/Postal Code
7530
Country
South Africa
Facility Name
Research Site
City
Pinelands
ZIP/Postal Code
7405
Country
South Africa
Facility Name
Research Site
City
Pretoria
ZIP/Postal Code
2
Country
South Africa
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
La Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Research Site
City
Santiago De Compostela-Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Research Site
City
Santiago de Compostela
ZIP/Postal Code
15702
Country
Spain
Facility Name
Research Site
City
Santiago de Compostela
ZIP/Postal Code
15705
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Research Site
City
Corby
ZIP/Postal Code
NN18 9EZ
Country
United Kingdom
Facility Name
Research Site
City
Enfield
ZIP/Postal Code
EN3 4GS
Country
United Kingdom
Facility Name
Research Site
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Research Site
City
High Wycombe
ZIP/Postal Code
HP11 2QW
Country
United Kingdom
Facility Name
Research Site
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
EC2Y 8EA
Country
United Kingdom
Facility Name
Research Site
City
Northwich
ZIP/Postal Code
CW9 7LS
Country
United Kingdom
Facility Name
Research Site
City
Northwood
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Research Site
City
Orpington
ZIP/Postal Code
BR5 3QG
Country
United Kingdom
Facility Name
Research Site
City
Preston
ZIP/Postal Code
PR2 9QB
Country
United Kingdom
Facility Name
Research Site
City
Rochdale
ZIP/Postal Code
OL11 4AU
Country
United Kingdom
Facility Name
Research Site
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Research Site
City
Shipley
ZIP/Postal Code
BD18 3SA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
A Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee
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