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

NCT04675034 | Completed Phase 2 Results DMC

• 2 other identifiers: D5680C000032020-003797-51
• Study Type: interventional
• Target: 345
• Locations: 5 countries
• Sites: 32

Brief Summary

This is a Phase IIb randomised, double-blind, placebo-controlled, dose-response study in participants 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 participants with moderate to severe chronic pain persistent for 3 months or more not adequately controlled by standard of care treatments.

Conditions

Painful Osteoarthritis of the Knee

Keywords

Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12

  Change from baseline in weekly average of daily NRS pain score to Week 12 is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = "no pain" to 10 = "most severe pain imaginable over the previous 24 hours". This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. A two-step multiple imputation procedure was used to address missing post-baseline scores.

  Baseline (Day -7 to Day -1, inclusive) through Week 12

Secondary Outcomes (29)

• Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12

  Week 0 (Day 1; baseline) through Week 12

• Change From Baseline in WOMAC Physical Function Subscale to Week 12

  Week 0 (Day 1; baseline) through Week 12

• Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12

  Week 0 (Day 1; baseline) through Week 12

• Change From Baseline in WOMAC Pain Subscale Over Time

  Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)

• Change From Baseline in WOMAC PF Subscale Over Time

  Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)

Study Arms (5)

MEDl7352 Dose 1

EXPERIMENTAL

Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period.

Drug: MEDI7352

MEDl7352 Dose 2

EXPERIMENTAL

Participants received 6 doses of SC MEDl7352 Dose 2 injection Q2W during a 12-week parallel-group treatment period.

Drug: MEDI7352

MEDl7352 Dose 3

EXPERIMENTAL

Participants received 6 doses of SC MEDl7352 Dose 3 injection Q2W during a 12-week parallel-group treatment period.

Drug: MEDI7352

MEDl7352 Dose 4

EXPERIMENTAL

Participants received 6 doses of SC MEDl7352 Dose 4 injection Q2W during a 12-week parallel-group treatment period.

Drug: MEDI7352

Placebo

PLACEBO COMPARATOR

Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period.

Other: Placebo

Interventions

MEDI7352 DRUG

Participants will receive SC injection of MEDI7352 as stated in arm description.

MEDl7352 Dose 1; MEDl7352 Dose 2; MEDl7352 Dose 3; MEDl7352 Dose 4

Placebo OTHER

Participants will receive SC injection of placebo as stated in arm description.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 nonsteroidal anti-inflammatory drugs (NSAID) or cyclooxygenase-2 (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.

You may not qualify if:

• Requires current treatment with another biologic therapeutic agent, disease-modifying antirheumatic drug (DMARD), or other immunosuppressants.
• Previously received any form of anti-nerve growth factor (NGF); received anti-tumour necrosis factors (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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (41)

Research Site

Frederiksberg, 2000, Denmark

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Tallinn, 10117, Estonia

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Tartu, 50708, Estonia

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Bad Doberan, 18209, Germany

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Leipzig, 04107, Germany

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Munich, 80809, Germany

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Bialystok, 15-351, Poland

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Bialystok, 15-897, Poland

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Bydgoszcz, 85-065, Poland

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Elblag, 82-300, Poland

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Gdynia, 81-338, Poland

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Lodz, 90-302, Poland

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Lublin, 20-607, Poland

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Poznan, 61-113, Poland

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Puławy, 24-100, Poland

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Staszów, 28-200, Poland

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Torun, 87-100, Poland

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Warsaw, 00-874, Poland

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Zamość, 22-400, Poland

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A Coruña, 15006, Spain

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Barcelona, 08035, Spain

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Madrid, 28034, Spain

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Málaga, 29010, Spain

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Sabadell, 08208, Spain

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Santiago de Compostela, 15702, Spain

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Santiago de Compostela, 15705, Spain

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Santiago de Compostela-Coruña, 15706, Spain

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Valencia, 46010, Spain

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Corby, NN18 9EZ, United Kingdom

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Enfield, EN3 4GS, United Kingdom

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Glasgow, G51 4TF, United Kingdom

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High Wycombe, HP11 2QW, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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London, EC2Y 8EA, United Kingdom

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Northwich, CW9 7LS, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Orpington, BR5 3QG, United Kingdom

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Preston, PR2 9QB, United Kingdom

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Rochdale, OL11 4AU, United Kingdom

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Salford, M6 8HD, United Kingdom

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Shipley, BD18 3SA, United Kingdom

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Related Links

• CSR Synopsis

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

Concomitant medication and therapies data do not necessarily evaluate the safety and are therefore not considered as outcome measures in this study.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

+1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants will be centrally assigned to randomised IP using an Interactive Response Technology/Randomisation and Trial Supply Management (IRT/RTSM) system. Before the study is initiated, telephone number and call-in directions for IRT and/or log in information and directions for RTSM will be provided to each site. The IRT/RTSM will provide investigator(s) or appropriate study personnel with kit identification number to be allocated to participant at IP dosing visit. Details for this will be described in IRT/RTSM user manual that will be provided to each centre. All participants, investigators, and study personnel involved in 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 study data to all study-related personnel. Unblinded AstraZeneca personnel who are not otherwise involved in study will prepare data for review and interim analyses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 investigational product (IP) are expected to complete the FU period.

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 19, 2020
• Study Start: December 2, 2020
• Primary Completion: August 16, 2023
• Study Completion: August 16, 2023
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

ES (2); GB (13); PL (13); DK (1); DE (3)