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AMZ001 for the Treatment of Knee Osteoarthritis Symptoms

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ClinicalTrials.gov Identifier: NCT03691844
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Amzell

Tracking Information
First Submitted Date  ICMJE September 18, 2018
First Posted Date  ICMJE October 2, 2018
Last Update Posted Date May 10, 2019
Actual Study Start Date  ICMJE October 4, 2018
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2018)
WOMAC pain sub-score [ Time Frame: baseline, week 4 ]
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee (double-blind treatment group only)
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
WOMAC pain sub-score [ Time Frame: week 4 ]
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-20 [extreme pain]) on target knee (double-blind treatment group only)
Change History Complete list of historical versions of study NCT03691844 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2018)
  • WOMAC total score and WOMAC function and stiffness [ Time Frame: baseline, week 4 ]
    Change from baseline in WOMAC total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20) (double-blind treatment group only)
  • ICOAP scores [ Time Frame: baseline, week 4 ]
    Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]) (double-blind treatment group only)
  • WOMAC pain weight-bearing score and non-weight-bearing score [ Time Frame: baseline, week 4 ]
    Change from baseline in WOMAC pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee (double-blind treatment group only)
  • Physical function [ Time Frame: baseline, week 4 ]
    Change from baseline in physical function assessed by the chair-stand test (double-blind treatment group only)
  • OMERACT-OARSI [ Time Frame: week 4 ]
    OMERACT-OARSI (Outcome Measures in Rheumatology - Osteoarthritis Research Society International) responder rate (double-blind treatment group only)
  • Total dose of rescue medication [ Time Frame: weeks 1 through 4 ]
    Total dose of rescue medication calculated as the sum of tablets used, based on pill counts (double-blind treatment group only)
  • Time between baseline and first use of rescue medication [ Time Frame: weeks 1 through 4 ]
    Time between baseline and first use of rescue medication (double-blind treatment group only)
  • WOMAC pain sub-score (dose comparison) [ Time Frame: baseline, week 4 ]
    Change from baseline in WOMAC pain sub-score (questions 1 to 5; score 0-20) between groups receiving AMZ001 QD and BID in the target knee (double-blind treatment group only)
  • ICOAP scores (dose comparison) [ Time Frame: baseline, week 4 ]
    Changes from baseline in constant and intermittent osteoarthritis pain assessed by ICOAP scores (0-44) between groups receiving AMZ001 QD and BID (double-blind treatment group only)
  • WOMAC pain weight-bearing score and non-weight-bearing score (dose comparison) [ Time Frame: baseline, week 4 ]
    Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) between groups receiving AMZ001 QD and BID (double-blind treatment group only)
  • Physical function (dose comparison) [ Time Frame: baseline, week 4 ]
    Changes from baseline in physical function assessed by the chair-stand test between AMZ001 QD and BID (double-blind treatment group only)
  • WOMAC total score and WOMAC function and stiffness (dose comparison) [ Time Frame: baseline, week 4 ]
    Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores between AMZ001 QD and BID (double-blind treatment group only)
  • Impact of osteoarthritis on daily living [ Time Frame: baseline, week 4 ]
    Changes from baseline in the impact of osteoarthritis on daily living as assessed by the Patient Global Assessment (PGA) score (0 [none] - 10 [extreme]) (double-blind treatment group only)
  • Work productivity [ Time Frame: baseline, week 4 ]
    Changes from baseline in work productivity and activity assessed by the Work Productivity and Active Impairment (WPAI scores 0-100% in four different categories: absenteeism, presenteesism, work productivity loss, and activity impairment) (double-blind treatment group only)
  • Change in quality of Life: EQ5D [ Time Frame: baseline, week 4 ]
    Changes from baseline in quality of life assessed by the EQ5D (score 0 [extremely poor] -100 [great] mm on a visual analogue scale) (double-blind treatment group only)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
  • WOMAC total score and WOMAC function and stiffness [ Time Frame: week 4 ]
    Change from baseline in WOMAC total score and WOMAC function (score 0-170) and stiffness (score 0-20) (double-blind treatment group only)
  • ICOAP scores [ Time Frame: week 4 ]
    Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]) (double-blind treatment group only)
  • WOMAC pain weight-bearing score and non-weight-bearing score [ Time Frame: week 4 ]
    Change from baseline in WOMAC pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee (double-blind treatment group only)
  • Physical function [ Time Frame: week 4 ]
    Change from baseline in physical function assessed by the chair-stand test (double-blind treatment group only)
  • OMERACT-OARSI [ Time Frame: week 4 ]
    OMERACT-OARSI (Osteoarthritis Research Society International) responder rate (double-blind treatment group only)
  • Total dose of rescue medication [ Time Frame: weeks 1 through 4 ]
    Total dose of rescue medication calculated as the sum of tablets used, based on pill counts (double-blind treatment group only)
  • Time between baseline and first use of rescue medication [ Time Frame: weeks 1 through 4 ]
    Time between baseline and first use of rescue medication (double-blind treatment group only)
  • WOMAC pain sub-score (dose comparison) [ Time Frame: week 4 ]
    Change from baseline in WOMAC pain sub-score (questions 1 to 5; score 0-20) between groups receiving AMZ001 QD and BID in the target knee (double-blind treatment group only)
  • ICOAP scores (dose comparison) [ Time Frame: week 4 ]
    Changes from baseline in constant and intermittent OA pain assessed by ICOAP scores (0-44) between groups receiving AMZ001 QD and BID (double-blind treatment group only)
  • WOMAC pain weight-bearing score and non-weight-bearing score (dose comparison) [ Time Frame: week 4 ]
    Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) between groups receiving AMZ001 QD and BID (double-blind treatment group only)
  • Physical function (dose comparison) [ Time Frame: week 4 ]
    Changes from baseline in physical function assessed by the chair-stand test between AMZ001 QD and BID (double-blind treatment group only)
  • WOMAC total score and WOMAC function and stiffness (dose comparison) [ Time Frame: week 4 ]
    Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores between AMZ001 QD and BID (double-blind treatment group only)
  • Impact of OA on daily living [ Time Frame: week 4 ]
    Changes from baseline in the impact of OA on daily living as assessed by the Patient Global Assessment (PGA) score (0 [none] - 10 [extreme]) (double-blind treatment group only)
  • Work productivity [ Time Frame: week 4 ]
    Changes from baseline in work productivity and activity assessed by the Work Productivity and Active Impairment (WPAI scores 0-100% in four different categories: absenteeism, presenteesism, work productivity loss, and activity impairment) (double-blind treatment group only)
  • Change in quality of Life: EQ5D [ Time Frame: week 4 ]
    Changes from baseline in quality of life assessed by the EQ5D (score 0 [extremely poor] -100 [great] mm on a visual analogue scale) (double-blind treatment group only)
Current Other Pre-specified Outcome Measures
 (submitted: October 9, 2018)
  • Safety endpoint (adverse events) [ Time Frame: weeks 1 through 4 ]
    Nature, incidence and severity of AEs
  • Safety endpoint (change in sitting systolic or diastolic blood pressure) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in sitting systolic or diastolic blood pressure)
  • Safety endpoint (change in sitting heart rate) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in sitting heart rate)
  • Safety endpoint (change in body temperature) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in body temperature)
  • Safety endpoint (12-lead ECG) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter 12-lead ECG (ventricular rate, PR, QRS, QT, QTc interval)
  • Safety endpoint (weight) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter weight
  • Safety endpoint (skin reactions) [ Time Frame: weeks 1 through 4 ]
    Nature, incidence, and severity of skin reactions on the application site
Original Other Pre-specified Outcome Measures
 (submitted: September 28, 2018)
  • Safety endpoint (adverse events) [ Time Frame: weeks 1 through 4 ]
    Nature, incidence and severity of AEs
  • Safety endpoint (change in sitting systolic or diastolic blood pressure) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in sitting systolic or diastolic blood pressure)
  • Safety endpoint (change in sitting heart rate) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in sitting heart rate)
  • Safety endpoint (change in body temperature) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter vital signs (change in body temperature)
  • Safety endpoint (12-lead ECG) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter 12-lead ECG (ventricular rate, PR, QRS, QT, QTc interval)
  • Safety endpoint (weight) [ Time Frame: weeks 1 through 4 ]
    Changes in laboratory safety parameter weight
  • Safety endpoint (skin reactions) [ Time Frame: weeks 1 through 4 ]
    Nature, incidence, and severity of skin reactions on the application site
  • Exploratory endpoint (WOMAC pain sub-score) [ Time Frame: week 4 ]
    Change from baseline in WOMAC pain sub-score (questions 1 to 5score 0 [no pain]-20 [extreme pain]) between groups receiving AMZ001 QD, BID and Voltaren® gel 1 % in the target knee
  • Exploratory endpoint (ICOAP scores) [ Time Frame: week 4 ]
    Changes from baseline in constant and intermittent OA pain assessed by ICOAP scores (score 0 [no pain]- 4 [extreme pain]) between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (WOMAC weight-bearing pain and non-weight bearing sub-score) [ Time Frame: week 4 ]
    Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (physical function) [ Time Frame: week 4 ]
    Changes from baseline in physical function assessed by the chair-stand test between AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (WOMAC score) [ Time Frame: week 4 ]
    Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores between AMZ001 QD, BID and Voltaren® gel 1 %
  • Exploratory endpoint (Pain Diary start) [ Time Frame: week 1 ]
    Change from baseline in the Pain Diary score between groups receiving AMZ001 QD, BID and Voltaren® gel 1 % in the target knee
  • Exploratory endpoint (Pain Diary end) [ Time Frame: week 4 ]
    Change from baseline in the weekly assessments of the Pain Diary score between groups receiving AMZ001 QD, BID and Voltaren® gel 1 % in the target knee
  • Exploratory endpoint (Clinically relevant pain reduction) [ Time Frame: weeks 1 through 4 ]
    Time to achieve a clinically relevant pain reduction defined as a decrease from baseline of at least 5 points out of 50 in the WOMAC pain sub-score in in each study group
  • Exploratory endpoint (Clinically relevant improvement) [ Time Frame: weeks 1 through 4 ]
    Time to achieve "moderate improvement" and time to achieve "high improvement" in OMERACT-OARSI response in each study group
  • Exploratory endpoint (OMERACT-OARSI) [ Time Frame: week 4 ]
    OMERACT-OARSI responder rate between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (amount of pain medication) [ Time Frame: weeks 1 through 4 ]
    Total dose of rescue medication calculated as the sum of tablets used, based on pill counts between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (time until pain medication) [ Time Frame: weeks 1 through 4 ]
    Time between baseline and first use of rescue medication in each study group
  • Exploratory endpoint (Work productivity) [ Time Frame: week 4 ]
    Changes from baseline in work productivity and activity assessed by the WPAI between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (Quality of life): EQ5D [ Time Frame: week 4 ]
    Changes from baseline in quality of life assessed by the EQ5D between groups receiving AMZ001 QD, BID, and Voltaren® gel 1 %
  • Exploratory endpoint (questionnaire assessment) [ Time Frame: week 4 ]
    Validation of subject's experience of satisfaction as measured by the satisfaction questionnaire. Also to use the study to validate these instruments being developed at this phase 2 stage of clinical development
  • Exploratory endpoint (questionnaire assessment) [ Time Frame: week 4 ]
    Validation of subject's experience of satisfaction as measured by the satisfaction of the assessment of pain as measured by the pain diary. Also to use the study to validate these instruments being developed at this phase 2 stage of clinical development
  • Exploratory endpoint (Comparison in diclofenac plasma levels) [ Time Frame: Weeks 2 and 4 ]
    Comparison in diclofenac plasma levels after application of AMZ001 QD, BID and Voltaren® gel 1 %
 
Descriptive Information
Brief Title  ICMJE AMZ001 for the Treatment of Knee Osteoarthritis Symptoms
Official Title  ICMJE A Placebo-controlled, Double-blind, Randomized, Trial of AMZ001 for the Treatment of Knee Osteoarthritis Symptoms
Brief Summary This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily.
Detailed Description This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily. Participants will be evaluated for osteoarthritis by X-ray images of the knees and one knee will be selected for treatment as the target knee. The study gel will be applied directly to that knee throughout the 4 weeks of the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
placebo-controlled, double-blind, randomized, parallel study
Masking: Double (Participant, Investigator)
Masking Description:
3 treatment arms will be double-blind, the 4th (comparator) will be single-blind
Primary Purpose: Treatment
Condition  ICMJE Osteoarthritis, Knee
Intervention  ICMJE
  • Drug: AMZ001
    diclofenac gel
  • Drug: Placebo
    Placebo
  • Drug: Comparator
    diclofenac gel
    Other Name: active comparator
Study Arms  ICMJE
  • Experimental: AMZ001 + Placebo
    on the target knee
    Intervention: Drug: AMZ001
  • Experimental: AMZ001
    on the target knee
    Intervention: Drug: AMZ001
  • Placebo Comparator: Placebo
    on the target knee
    Intervention: Drug: Placebo
  • Active Comparator: Comparator
    Diclofenac gel on the target knee
    Intervention: Drug: Comparator
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 28, 2018)
440
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2019
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and X-ray criteria.
  2. Pain score rated on an 11-point numerical rating scale of the target knee of ≥ 20 and ≤ 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening, after washout of any pain relief medication.
  3. Women of child-bearing potential must use at least an acceptably effective method of contraception from enrollment up to at least 3 months after the study end.
  4. Knee pain in the target knee for 14 days of the preceding month (knee pain due to osteoarthritis and not due to another condition such as bursitis, tendinitis, etc.) based on subject report.
  5. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral or topical NSAID prescribed by physician for 30 days prior to the Screening Visit and/or prescribed over-the-counter.
  6. Except for osteoarthritis, in reasonably good health as determined by the Investigator.

Exclusion Criteria:

  1. Known or suspected hypersensitivity to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the components in either of the investigation products, or any physical impediment to gel application on the target knee.
  2. Injection of corticosteroids or hyaluronic acid in the target knee within 6 months of screening or into any other joint within 30 days of screening.
  3. High dose oral/injected corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
  4. Major surgery or arthroscopy of the target knee within the previous year prior to screening.
  5. Planned surgery of the target knee within the next 3 months.
  6. Presence of an additional non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or pseudo-gout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug.
  7. Medical history of coronary artery bypass graft surgery.
  8. Current cancer or treatment for cancer within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area.
  9. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint of the target knee.
  10. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in hip(s) exceeds that of the target knee using the WOMAC Hip Pain subscore, presence of significant back pain, or at least one migraine attack within the past 12 months before screening, as reported by the subject.
  11. Body Mass Index > 45.0 kg/m2.
  12. Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of gel application, or significant skin disease including psoriasis, as judged by the investigator.
  13. Known presence of a ulcer or any gastrointestinal bleeding within 6 months prior to screening.
  14. Use of moderate or higher doses of opioid medication for the treatment of pain within 6 weeks before the screening visit.
  15. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the screening visit.
  16. History of alcohol or drug abuse within the past year prior to randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amzell 31 23 55 60 460 amzell-disclosure@amzell.com
Listed Location Countries  ICMJE Czechia,   Denmark,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03691844
Other Study ID Numbers  ICMJE AMZ001-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amzell
Study Sponsor  ICMJE Amzell
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amzell
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP