A Study of MEDI7352 in Painful Osteoarthritis of the Knee

A Randomised, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee

The purpose of this study is to assess the safety, drug levels and effects on the body of MEDI7352, in subjects with painful osteoarthritis of the knee.

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Biological: MEDI7352 for IV infusion; Biological: Placebo for IV infusion; Biological: MEDI7352 for Subcutaneous Injection; Biological: Placebo for Subcutaneous Injection

Detailed Description

An interleaved SAD/MAD Study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI7352 in subjects with painful osteoarthritis of the knee.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Research Site
• Sweden
  • Göteborg, Sweden, 413 45
    • Research Site
  • Stockholm, Sweden, 141 86
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT2 7BA
    • Research Site
  • London, United Kingdom, NW10 7EW
    • Research Site
  • Manchester, United Kingdom, M13 9NQ
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female subjects with painful osteoarthritis (OA) of the knee. Female subjects must be postmenopausal or surgically sterile.
• Body weight between 50kg and 145kg
• Willing and able to comply with the requirements of the protocol

Exclusion Criteria:

• Current treatment with another biologic therapeutic agent
• Current of historical diagnosis of RA
• Current diagnosis of an immunological condition that is associated with another form of arthritis in addition to OA, including traumatic arthritis or a seronegative spondyloarthropathy
• At risk of destructive arthropathy, including Rapidly Progressive Osteoarthritis (RPOA), osteonecrosis, spontaneous osteonecrosis of the knee, subchondral insufficiency fractures, hip dislocation and pathological fracture
• Presence of clinically significant neuropathy or other clinically significant disorder involving abnormal peripheral sensation.
• Current serious or unstable clinically important illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI7352 IV; Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.	Biological: MEDI7352 for IV infusion; MEDI7352 for IV infusion
Placebo Comparator: IV Placebo; Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.	Biological: Placebo for IV infusion; IV Placebo infusion
Experimental: MEDI7352 Subcutaneous Injection; 1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.	Biological: MEDI7352 for Subcutaneous Injection; MEDI7352 for subcutaneous injection
Placebo Comparator: Subcutaneous Placebo; 1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.	Biological: Placebo for Subcutaneous Injection; Subcutaneous Placebo Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352	Adverse events, serious adverse events,	All visits from screening up to 56 days post single dose/84 days post multiple dose
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352	Clinical laboratory assessments (serum chemistry, hematology, urinalysis)	All visits from screening up to 56 days post single dose/84 days post multiple dose
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352	12 Lead electrocardiogram (including QTc, QRS, PR intervals and ventricular rate)	All visits from screening up to 56 days post single dose/84 days post multiple dose
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352	Vital signs (systolic and diastolic BP), heart rate	All visits from screening up to 56 days post single dose/84 days post multiple dose
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352	MRI	At screening and at follow up visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma drug concentration versus time curves for MEDI7352	Area under the plasma drug concentration versus time curves from zero to infinity and to last observation (AUC 0-inf; AUC 0-t).	All visits from screening up to 56 days post single dose/84 days post multiple dose
Maximum observed plasma drug concentration (Cmax) of MEDI7352	Maximum observed plasma drug concentration (Cmax).	All visits from screening up to 56 days post single dose/84 days post multiple dose
Time to maximum observed plasma drug concentration (Tmax) of MEDI7352	Time to maximum observed plasma drug concentration (Tmax).	All visits from screening up to 56 days post single dose/84 days post multiple dose
Terminal plasma elimination half-life (t1/2) of MEDI7352	Terminal plasma elimination half-life (t1/2).	All visits from screening up to 56 days post single dose/84 days post multiple dose
Apparent clearance (CL/F).	Apparent clearance (CL/F).	All visits from screening up to 56 days post single dose/84 days post multiple dose
The presence of anti-drug antibodies (ADAs) to MEDI7352	The incidence of anti-drug antibodies (a measure of the body's immune response to the drug).	All visits from screening up to 56 days post single dose/84 days post multiple dose
Pain Numerical Rating Scale (NRS)	Numerical Rating Scale (NRS)	All visits from screening up to 56 days post single dose/84 days post multiple dose
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.	All visits from screening up to 56 days post single dose/84 days post multiple dose
Patients' Global Impression of Change Scale (PGIC)	Patients' Global Impression of Change Scale (PGIC)	All visits from screening up to 56 days post single dose/84 days post multiple dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: David Bell, MB BCh BAO MRCGP FFPM, Biokinetics

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2015
• Primary Completion (Actual): December 23, 2020
• Study Completion (Actual): December 23, 2020

Study Registration Dates

• First Submitted: July 2, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Chronic Pain
• Other Study ID Numbers: D5680C00001

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.
• 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 de-identified 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.

Drug and device information, study documents

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