Clinical trial NCT04675034: A Study of the Efficacy and Safety of MEDI7352 in Participants With Painful Osteoarthritis of the Knee
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Painful Osteoarthritis of the Knee
Keywords: Osteoarthritis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-12-19
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 investigational product (IP) are expected to complete the FU period.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

Exclusion Criteria:

1. Requires current treatment with another biologic therapeutic agent, disease-modifying antirheumatic drug (DMARD), or other immunosuppressants.
2. 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).
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.

Primary outcomes:
measure: Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12
timeFrame: Baseline (Day -7 to Day -1, inclusive) through Week 12
Secondary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12
timeFrame: Week 0 (Day 1; baseline) through Week 12
measure: Change From Baseline in WOMAC Physical Function Subscale to Week 12
timeFrame: Week 0 (Day 1; baseline) through Week 12
measure: Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12
timeFrame: Week 0 (Day 1; baseline) through Week 12
measure: Change From Baseline in WOMAC Pain Subscale Over Time
timeFrame: 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)
measure: Change From Baseline in WOMAC PF Subscale Over Time
timeFrame: 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)
measure: Change From Baseline in WOMAC Overall Score Over Time
timeFrame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
measure: Change From Baseline in WOMAC Stiffness Scores Over Time
timeFrame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
measure: Change From Baseline in PGA of OA Over Time
timeFrame: Baseline, Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
measure: Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition
timeFrame: Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
measure: Percentage of Participants With Improvement of >= 2 Points in PGA of OA
timeFrame: Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
measure: Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
measure: Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
measure: Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time
timeFrame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
measure: Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time
timeFrame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
measure: Serum Concentration of MEDI7352
timeFrame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352
timeFrame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
measure: ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline
timeFrame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 41 weeks (maximum observed duration)
measure: Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs
timeFrame: Day 1 through 41 weeks (maximum observed duration)
measure: Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination
timeFrame: Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 18 (Day 126), 28 (Day 168), 32 (Day 224), and 36 (Day 252)
measure: Total Neuropathy Score-Nurse (TNSn) Over Time
timeFrame: Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 196), and 32 (Day 224)
measure: Change From Baseline in Weight (kg) to Week 12
timeFrame: Baseline (Day -45 to -1) and Week 12
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 1 through 41 weeks (maximum observed duration)
measure: Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score
timeFrame: Baseline (Day 1; Week 0) and Day 252 (Week 36)
measure: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)
timeFrame: Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 168), and 32 (Day 224)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 41 weeks (maximum observed duration)
measure: Change From Baseline in C-reactive Protein Level to Week 12
timeFrame: Baseline (Day -7 to -1, inclusive) and Week 12
measure: Number of Participants With Injection Site Reactions
timeFrame: Day 1 through 41 weeks (maximum observed duration)
measure: Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints
timeFrame: Baseline (Day -45 to -1) and Week 32
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Bad Doberan
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Munich
country: Germany
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Elblag
country: Poland
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Puławy
country: Poland
facility: Research Site
city: Staszów
country: Poland
facility: Research Site
city: Toruń
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Zamosc
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: La Coruña
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Sabadell
country: Spain
facility: Research Site
city: Santiago De Compostela-Coruña
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Corby
country: United Kingdom
facility: Research Site
city: Enfield
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: High Wycombe
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Northwich
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Orpington
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
city: Rochdale
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Shipley
country: United Kingdom
facility: Research Site
Study officials:
References: