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A Phase 2 Clinical Trial Examining the Effects on Osteoarthritic Knee Pain of CGS-200-1, CGS-200-5 and Vehicle Control

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ClinicalTrials.gov Identifier: NCT03528369
Recruitment Status : Completed
First Posted : May 17, 2018
Results First Posted : December 17, 2019
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Propella Therapeutics

Tracking Information
First Submitted Date  ICMJE March 20, 2018
First Posted Date  ICMJE May 17, 2018
Results First Submitted Date  ICMJE December 2, 2019
Results First Posted Date  ICMJE December 17, 2019
Last Update Posted Date April 8, 2020
Actual Study Start Date  ICMJE May 14, 2018
Actual Primary Completion Date October 14, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2019)
Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 [ Time Frame: 35 days after the last dose of study drug on Day 4 ]
The Primary Efficacy endpoint of this study will be to examine the extent of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, relative to baseline, provided by once daily, one-hour application of Vehicle (CGS-200-0), CGS-200-1 and CGS-200-5 at Baseline (< 30 minutes prior to first daily application) and Day 35 (31 days after fourth daily application). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score is 5 questions relating to pain that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 500. Reduction in pain is expressed as a difference from baseline to Study Day 35. Positive numbers indicate increases and negative numbers indicate decreases. .
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2018)
  • Primary Efficacy Endpoint: Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 [ Time Frame: 35 days ]
    The Primary Efficacy endpoint of this study will be to examine the extent of reduction in the WOMAC pain score, relative to baseline, provided by once daily, one-hour application of Vehicle (CGS-200-0), CGS-200-1 and CGS-200-5 at Baseline (< 30 minutes prior to first daily application) and Day 35 (31 days after fourth daily application).
  • Primary Safety Endpoint #1: Frequency and severity of skin reaction Adverse Events (erythema, scaling, pruritus, or other) of clinical concern. [ Time Frame: 35 days ]
    The application of the study drug does not produce skin reactions (erythema, scaling, pruritus, or other) to a degree that is clinically of concern. Scoring of erythema and scaling at the application sites and of pruritus will be assessed per specified scoring systems.
  • Primary Safety Endpoint #2: Frequency of Serious Adverse Events (SAEs) related to the study treatment [ Time Frame: 35 days ]
    No SAE's either possibly, probably or definitely associated with study treatments.
  • Primary Safety Endpoint #3(a): The proportion of subjects with other than minimal - mild (Grade 1 or Grade 2) hematologic toxicities is not significantly different. [ Time Frame: 35 days ]
    Change, for any cell type or hematology parameter, from within normal limits to above or below normal limits. Grade per Rheumatology Common Toxicity Criteria v2.0. (RCTC) is amount of change. If high or low at screening, then change such that toxicity grade increases from level a screening. Comparison is between the CGS-200-5 group to the CGS-200-0 group or comparing the CGS-200-1 group to the CGS-200-0 group.
  • Primary Safety Endpoint #3(b): The proportion of subjects with other than minimal - mild (Grade 1 or Grade 2) serum chemistry toxicities is not significantly different. [ Time Frame: 35 days ]
    Change, for any analyte, from within normal limits to above or below normal limits. Grade per RCTC is amount of change. If high or low at screening, then change such that toxicity grade increases from level a screening. Comparison is between the CGS-200-5 group to the CGS-200-0 group or comparing the CGS-200-1 group to the CGS-200-0 group.
  • Primary Safety Endpoint #3(c): The proportion of subjects with other than minimal - mild (Grade 1 or Grade 2) urinalysis toxicities is not significantly different. [ Time Frame: 35 days ]
    Change, for any analyte, from within normal limits to above or below normal limits. Grade per RCTC is amount of change. If high or low at screening, then change such that toxicity grade increases from level a screening. Comparison is between the CGS-200-5 group to the CGS-200-0 group or comparing the CGS-200-1 group to the CGS-200-0 group.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2019)
  • Secondary Efficacy Endpoint #1: Extent of Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 5, 19, 64 and 94. [ Time Frame: Days 5, 19, 65 and 94 after the last dose of study drug on Day 4 ]
    The extent of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, relative to baseline, provided by once daily, one-hour application of CGS-200-0, CGS-200-1 and CGS-200-5 from Baseline to Day 5, 19, 64 and Day 94. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score is 5 questions relating to pain that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 500. Positive numbers indicate increases and negative numbers indicate decreases.
  • Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. [ Time Frame: 60 minutes after study drug application on Study Days 1,2,3,4 ]
    The average amount of burning-sting pain as reported by the subject using a 0 - 10 numerical rating scale (NRS). Higher scores indicate more pain.
  • Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. [ Time Frame: Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4 ]
    Day 5, 19, 35, 64 and 94 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score is 2 questions relating to stiffness that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 200. Positive numbers indicate increases and negative numbers indicate decreases.
  • Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. [ Time Frame: Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4 ]
    Day 5, 19, 35, 64 and 94 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function score is 17 questions relating to physical function that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 1700. Positive numbers indicate increases and negative numbers indicate decreases.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2018)
  • Secondary Efficacy Endpoint #1: Extent of reduction in WOMAC pain score from Baseline to Day 5, Day 19, Day 64, and Day 94 [ Time Frame: 5 days, 19 days, 64 days, and 94 days ]
    The extent of reduction in the WOMAC pain score, relative to baseline, provided by once daily, one-hour application of CGS-200-0, CGS-200-1 and CGS-200-5 from Baseline to Day 5, Baseline to Day 19, Baseline to Day 64, and Baseline to Day 94.
  • Secondary Efficacy Endpoint #2: WOMAC total, stiffness, and function scores from Baseline to Day 5, Day 19, Day 64, and Day 94 [ Time Frame: 5 days, 19 days, 64 days, and 94 days ]
    Day 5, 19, 35, 64 and 94 WOMAC scores on the stiffness and function subscales as well as total WOMAC score (including the WOMAC pain score).
  • Secondary Safety Endpoint #1: Frequency of specific Adverse Events (AEs) by study arm [ Time Frame: 94 days ]
    The distribution by study arms of specific AEs (i.e.: local application site reactions, and other AEs (inclusive of findings for hematology, serum chemistry and urinalysis).
  • Secondary Safety Endpoint #2: Usage of concomitant pain medications [ Time Frame: 94 days ]
    Evaluate the amount of concomitant pain medications used overtime
  • Secondary Tolerability Endpoint #1: Patient reported burning-stinging pain (BSP) during application of the study drug. [ Time Frame: 60 minutes ]
    The application of study drug does not produce BSP at the application site to a degree that is not acceptable to the subject. BSP at the application site will be assessed using a 0 - 10 numerical rating scale (NRS) without guideposts. "Acceptability" of BSP will be queried per subject at the end of each application period.
  • Secondary Tolerability Endpoint #2: Severity of pruritus during study drug application and up to 24 hours after application, as measured by numerical scale provided in Appendix F of the protocol. [ Time Frame: 1 day ]
    The application of the study drug does not produce pruritus during application or in the 24 hrs post-application to a degree that is not acceptable to the subject or, if bothersome to the subject, cannot be managed by application of ice or a cold pack or compress.
Current Other Pre-specified Outcome Measures
 (submitted: December 16, 2019)
  • Number of Subjects With Skin Reactions of Erythema or Pruritus. [ Time Frame: Study Day 1 through Study Day 35 after the first application of study drug (Study Day 1) ]
    Investigator reports of erythema or pruritus at the site of study drug application.
  • Number of Subjects With Durability of Efficacy Response [ Time Frame: Days 35, 64 and 94 day after the last dose of study drug on Study Day 4 ]
    Subjects who had a clinical response (i.e., reduction of at least 50% in WOMAC pain score) at the Day 5 visit and who remained at this reduction of pain score or lower at Days 19, 35, 64, and the Day 94 visit were considered to have a durable clinical response through Day 94. Subjects who had a clinical response at no more than one of the post Day 5 visits were considered to have a durable response through the last day at which reduction in WOMAC pain score is at least 50%. Subjects who had less than 50% WOMAC pain score reduction on two or more of the post Day 5 visits were considered to have failed to achieve a durable clinical response.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Clinical Trial Examining the Effects on Osteoarthritic Knee Pain of CGS-200-1, CGS-200-5 and Vehicle Control
Official Title  ICMJE A Phase 2 Double-Blind Clinical Trial to Examine the Comparative Effects on Osteoarthritic Knee Pain of CGS-200-1 (1% Capsaicin Topical Liquid), CGS-200-5 (5% Capsaicin Topical Liquid), and CGS-200-0 (Vehicle, No Capsaicin)
Brief Summary This is a multi-center, randomized, double-blind clinical trial to examine the comparative effects on OAKP of CGS-200-1 (1% Capsaicin content) (N=40), CGS-200-5 (5% Capsaicin content) (N=40), and CGS-200 Vehicle (no Capsaicin) (N=40) in subjects with OA of the knees according to the 1986 American College of Rheumatology (ACR) criteria. Assigned doses will be applied at the clinic for 60 minutes on each of four consecutive days.
Detailed Description

Subjects will be randomized to one of the three Arms in this study: CGS-200-1 or CGS-200-5 or CGS-200 Vehicle (CGS-200-0). All subjects will receive 4 consecutive days of treatment and will then be followed up until the Day 94 visit.

Even though both knee(s) will receive application of study test materials, with regard to reduction in WOMAC pain and VAS pain score associated with study treatments, only one knee will be indicated as the "Study Knee". This will be the knee with the highest WOMAC pain score at screening. If both knees have equal WOMAC pain scores at baseline, then the right knee will be considered the "Study Knee" with regard to WOMAC pain and VAS pain score reduction.

Data will be collected from Day 1 through Day 5 and then again on Days 19, 35, 64 and 94 for efficacy, tolerability, and safety measures. The Investigators, all site staff and Clinical Research Organization (CRO) personnel (except the Medical Monitor providing safety oversight) directly involved in the study will remain blinded to the treatment assignment throughout the trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Osteoarthritis, Knee
  • Pain
Intervention  ICMJE
  • Drug: CGS-200-1
    CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.
    Other Name: CGS-200 (1% capsaicin)
  • Drug: CGS-200-5
    CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.
    Other Name: CGS-200 (5% capsaicin)
  • Drug: CGS-200 Vehicle
    CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
    Other Name: CGS-200 (0% capsaicin)
Study Arms  ICMJE
  • Experimental: CGS-200-1
    CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4.
    Intervention: Drug: CGS-200-1
  • Experimental: CGS-200-5
    CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4.
    Intervention: Drug: CGS-200-5
  • Sham Comparator: CGS-200 Vehicle
    CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4.
    Intervention: Drug: CGS-200 Vehicle
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 Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2018)
122
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2018)
120
Actual Study Completion Date  ICMJE December 30, 2018
Actual Primary Completion Date October 14, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Osteoarthritis (OA) of both knees;
  • OA of both knees must be confirmed by tibiofemoral joint radiographs obtained within the past 6 months;
  • Rheumatoid factor (RF) negative and Erythrocyte sedimentation rate (ESR) <40 mm/hr;
  • Chronic knee pain in at least 1 knee for > 3 months;
  • WOMAC pain score of > 250 (using VAS WOMAC format) at screening, and at baseline, in at least one knee;
  • Knee pain score of > 5 on the NRS pain scale at screening, and at baseline, in at least one knee;
  • Knee pain is not potentially due to acute trauma unrelated to OA (no acute traumatic knee injury in medical history);
  • No burning-stinging pain, unrelated to subject's knee pain, at intended site of application;
  • Knee pain must be greater than pain in any other part of subject's body;
  • American College of Rheumatology (ACR) global functional status I, II, or III (excluding IV).

Exclusion Criteria:

  • Spontaneously improving or rapidly deteriorating OA of the knee;
  • Rheumatoid or psoriatic arthritis, or a form of arthritis (e.g. gout, pseudogout), Paget's disease of bone, or any other disease affecting the joints that are inconsistent with a diagnosis of idiopathic OA;
  • Labile or poorly controlled hypertension;
  • Use of steroids for 1 month prior to screening, or intraarticular-visco-supplementation within 3 months prior to screening;
  • Used any capsaicin-containing product on or in the vicinity of the knee within 4 weeks prior to screening;
  • Used topically applied products (including emollients or moisturizers) on or in the vicinity of the knees or shaved the knees within 2 days prior to the first application of study drug; or an open wound near the knee; cutaneous erythema or edema; any inflammatory skin lesions such as eczema or psoriasis; cutaneous infections; or any other compromise of the skin;
  • Requires or anticipates any surgical procedure within 3 months prior to screening, has had surgery on the affected joint within 6 months prior to screening, has a prosthesis in either knee, or would require surgery while participating in the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03528369
Other Study ID Numbers  ICMJE VZU00025
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
Plan to Share IPD: No
Responsible Party Propella Therapeutics
Study Sponsor  ICMJE Propella Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Vice President Clinical Operations Vizuri Health Sciences
PRS Account Propella Therapeutics
Verification Date December 2019

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