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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04675034
• Collaborator: (none)
• Enrollment: 300
• Locations: 93
• Arms: 5
• Anticipated Duration (Months): 35.1
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Painful Osteoarthritis of the Knee	Biological: MEDI7352; Biological: MEDI7352; Biological: MEDI7352; Biological: MEDI7352; Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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.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: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
• Primary Purpose: Treatment
• 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:
• Actual Study Start Date: Dec 2, 2020
• Anticipated Primary Completion Date: Nov 5, 2023
• Anticipated Study Completion Date: Nov 5, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Numerical Rating Scale pain scores [12 weeks]

   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

1. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale from [12 Weeks]

   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

2. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function [12 Weeks]

   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

3. Physician Global Assesment (PGA of OA) [12 Weeks]

   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).

4. ADA titre [12 weeks]

   Serum concentration of ADA titre

5. Adverse Events [Through study completion, an average of 10 months]

   Number of Participants with adverse events and serious adverse events

6. Anti-drug Antibodies (ADA) [through study completion, an average of 10 months]

   Presence of ADA to MEDI7352

7. concentration of MEDI7352 [through study completion, an average of 10 months]

   Serum concentration of MEDI7352

8. Percentage of responders as measured by the OARSI responder index using the OMERACT-OARSI [Weeks 2, 4, 8, 12, and 18]

   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

9. Vital Signs (Blood Pressure) in mmHg [Through study completion, an average of 10 months]

   Change from baseline supine and standing blood pressure in all participants

10. Vital Signs (Heart Rate) in beats per minute [Through study completion, an average of 10 months]

    Change from baseline heart rate in all participants

11. Vital Signs (Respiratory Rate) in breaths per minute [Through study completion, an average of 10 months]

    Change from baseline respiratory rate in all participants

12. Vital Signs (Temperature) in °C [Through study completion, an average of 10 months]

    Change from baseline temperature measurements in all participants

13. Clinical laboratory assessments [Through study completion, an average of 10 months]

    Number of Participants with abnormal laboratory values

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Montclair	California	United States	91763
2	Research Site	Clearwater	Florida	United States	33756
3	Research Site	Coral Gables	Florida	United States	33134
4	Research Site	Fort Myers	Florida	United States	33912
5	Research Site	Jupiter	Florida	United States	33458
6	Research Site	Tampa	Florida	United States	33606
7	Research Site	Valparaiso	Indiana	United States	46383
8	Research Site	Hazelwood	Missouri	United States	63042
9	Research Site	Lincoln	Nebraska	United States	68516
10	Research Site	Blue Ash	Ohio	United States	45242
11	Research Site	Oklahoma City	Oklahoma	United States	73103
12	Research Site	Duncansville	Pennsylvania	United States	16635
13	Research Site	Rapid City	South Dakota	United States	57702
14	Research Site	Dallas	Texas	United States	75231
15	Research Site	Houston	Texas	United States	77034
16	Research Site	Houston	Texas	United States	77055
17	Research Site	Burke	Virginia	United States	22015
18	Research Site	Bellevue	Washington	United States	98007
19	Research Site	London	Ontario	Canada	N6C 0A5
20	Research Site	Sherbrooke	Quebec	Canada	J1L 0H8
21	Research Site	Trois-Rivieres	Quebec	Canada	G8Z 1Y2
22	Research Site	Quebec		Canada	G1N 4V3
23	Research Site	Quebec		Canada	G1V 3M7
24	Research Site	Frederiksberg		Denmark	2000
25	Research Site	Tallinn		Estonia	10117
26	Research Site	Tartu		Estonia	50708
27	Research Site	Bad Doberan		Germany	18209
28	Research Site	Freiburg		Germany	79106
29	Research Site	Freiburg		Germany	79106
30	Research Site	Hamburg		Germany	20095
31	Research Site	Hamburg		Germany	22143
32	Research Site	Leipzig		Germany	04107
33	Research Site	Leipzig		Germany	04107
34	Research Site	Munich		Germany	80809
35	Research Site	Munich		Germany	80809
36	Research Site	Bialystok		Poland	15-897
37	Research Site	Białystok		Poland	15-351
38	Research Site	Bydgoszcz		Poland	85-065
39	Research Site	Bydgoszcz		Poland	85-065
40	Research Site	Elblag		Poland	82-300
41	Research Site	Gdynia		Poland	81-338
42	Research Site	Lodz		Poland	90-302
43	Research Site	Lodz		Poland	90-302
44	Research Site	Lublin		Poland	20-607
45	Research Site	Poznan		Poland	61-113
46	Research Site	Puławy		Poland	24-100
47	Research Site	Puławy		Poland	24-100
48	Research Site	Staszów		Poland	28-200
49	Research Site	Staszów		Poland	28-200
50	Research Site	Toruń		Poland	87-100
51	Research Site	Warszawa		Poland	00-874
52	Research Site	Zamosc		Poland	22-400
53	Research Site	Cape Town		South Africa	7130
54	Research Site	Cape Town		South Africa	7500
55	Research Site	Cape Town		South Africa	7550
56	Research Site	Durban		South Africa	4319
57	Research Site	Johannesburg		South Africa	2013
58	Research Site	Paarl		South Africa	7647
59	Research Site	Pinelands		South Africa	7405
60	Research Site	Pretoria		South Africa	2
61	Research Site	Stellenbosch		South Africa	7600
62	Research Site	Barcelona		Spain	08035
63	Research Site	Barcelona		Spain	08035
64	Research Site	Cordoba		Spain	14004
65	Research Site	Cordoba		Spain	14004
66	Research Site	Galdakao		Spain	48960
67	Research Site	La Coruña		Spain	15006
68	Research Site	Madrid		Spain	28034
69	Research Site	Madrid		Spain	28034
70	Research Site	Malaga		Spain	29010
71	Research Site	Sabadell		Spain	08208
72	Research Site	Santiago De Compostela-Coruña		Spain	15706
73	Research Site	Santiago de Compostela		Spain	15702
74	Research Site	Santiago de Compostela		Spain	15705
75	Research Site	Valencia		Spain	46010
76	Research Site	Cambridge		United Kingdom	CB2 0QQ
77	Research Site	Corby		United Kingdom	NN18 9EZ
78	Research Site	Coventry		United Kingdom	CV3 4FJ
79	Research Site	Enfield		United Kingdom	EN3 4GS
80	Research Site	Glasgow		United Kingdom	G51 4TF
81	Research Site	High Wycombe		United Kingdom	HP11 2QW
82	Research Site	Leeds		United Kingdom	LS7 4SA
83	Research Site	Leeds		United Kingdom	LS7 4SA
84	Research Site	London		United Kingdom	EC2Y 8EA
85	Research Site	London		United Kingdom	EC2Y 8EA
86	Research Site	Northwich		United Kingdom	CW9 7LS
87	Research Site	Northwood		United Kingdom	HA6 2RN
88	Research Site	Orpington		United Kingdom	BR5 3QG
89	Research Site	Preston		United Kingdom	PR2 9QB
90	Research Site	Rochdale		United Kingdom	OL11 4AU
91	Research Site	Rochdale		United Kingdom	OL11 4AU
92	Research Site	Salford		United Kingdom	M6 8HD
93	Research Site	Shipley		United Kingdom	BD18 3SA

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04675034
• Other Study ID Numbers: D5680C00003
• First Posted: Dec 19, 2020
• Last Update Posted: Aug 25, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Osteoarthritis
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Pain

Study Results

No Results Posted as of Aug 25, 2022