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

Painful Osteoarthritis of the Knee Clinical Trial

— 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:

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04675034
• Other study ID #: D5680C00003
• Secondary ID: 2020-003797-51
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2020
• Est. completion date: August 16, 2023

Study information

• Verified date: September 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: August 16, 2023
• Est. primary completion date: August 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee
• Pain
• Painful Osteoarthritis of the Knee

Intervention

Biological:
• MEDI7352
Dose A: MEDI7352 Q2W
• MEDI7352
Dose B: MEDI7352 Q2W
• MEDI7352
Dose C: MEDI7352 Q2W
• MEDI7352
Dose D: MEDI7352 Q2W
• Placebo
Placebo to match MEDI7352 Q2W

Locations

Country	Name	City	State
Denmark	Research Site	Frederiksberg
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Germany	Research Site	Bad Doberan
Germany	Research Site	Leipzig
Germany	Research Site	Munich
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Elblag
Poland	Research Site	Gdynia
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Pulawy
Poland	Research Site	Staszów
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Zamosc
South Africa	Research Site	Bellville
South Africa	Research Site	Pinelands
South Africa	Research Site	Pretoria
Spain	Research Site	Barcelona
Spain	Research Site	La Coruña
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Sabadell
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Santiago De Compostela-Coruña
Spain	Research Site	Valencia
United Kingdom	Research Site	Corby
United Kingdom	Research Site	Enfield
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	High Wycombe
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Northwich
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Orpington
United Kingdom	Research Site	Preston
United Kingdom	Research Site	Rochdale
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Shipley

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Denmark,  Estonia,  Germany,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	ADA titre	Serum concentration of ADA titre	12 weeks
Secondary	Adverse Events	Number of Participants with adverse events and serious adverse events	Through study completion, an average of 10 months
Secondary	Anti-drug Antibodies (ADA)	Presence of ADA to MEDI7352	through study completion, an average of 10 months
Secondary	concentration of MEDI7352	Serum concentration of MEDI7352	through study completion, an average of 10 months
Secondary	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
Secondary	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
Secondary	Vital Signs (Heart Rate) in beats per minute	Change from baseline heart rate in all participants	Through study completion, an average of 10 months
Secondary	Vital Signs (Respiratory Rate) in breaths per minute	Change from baseline respiratory rate in all participants	Through study completion, an average of 10 months
Secondary	Vital Signs (Temperature) in °C	Change from baseline temperature measurements in all participants	Through study completion, an average of 10 months
Secondary	Clinical laboratory assessments	Number of Participants with abnormal laboratory values	Through study completion, an average of 10 months