Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack (NCT NCT04067492)

Enrollment was conducted at 11 clinical sites in Russian Federation. 54 subjects were screened and 47 subjects were enrolled (randomized) and treated, 44 subjects completed the study. The Safety Population and Efficacy Population included data from all 47 randomized patients to assess safety, treatment efficacy and pharmacodynamics.

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack

Change in pain intensity in the assessed joint 72 hours after the initiation of treatment with the test drug measured using the Visual Analogue Scale (VAS) in comparison to baseline. VAS is a hard copy 100 mm scale with the indications: "Absence of pain" on the left side of the scale (0 mm point) and "The most severe pain ever experienced" on the right side of the scale (100 mm point)) The better outcome would be "Absence of pain", the worse outcome would be "The most severe pain ever experienced".

Change in pain intensity in the assessed joint in 15, 30, 45 minutes, 1, 1.5, 2, 4, 8, 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug measured using the Visual Analogue Scale (VAS) and compared to baseline. VAS is a hard copy 100 mm scale with the indications: "Absence of pain" on the left side of the scale (0 mm point) and "The most severe pain ever experienced" on the right side of the scale (100 mm point)) The better outcome would be "Absence of pain", the worse outcome would be "The most severe pain ever experienced".

Proportion of patients who assessed the response to therapy with the test drug as "Excellent" or "Good" in 15, 30, 45 minutes, 1, 1.5, 2, 4, 8, 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug. The patient's response to therapy was assessed in the form of frequency tables by assessment point and therapy group. The rates of the response were specified in the evaluation form as: "Excellent", "Good", "Fair", "Weak", "Poor" (where "excellent" represents the best possible response to treatment and "poor" indicates the worst treatment response).

Change in the rate of swelling of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. The rates of swelling were specified in the evaluation form as: "absence" = no swelling, "mild" = palpable swelling, "moderate" = visible swelling, "severe" = bulging outside the joint (where "severe" represented the worst possible degree of swelling and "absence" was the best outcome).

Change in the rate of tenderness of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. Tenderness degrees: "absent" = no tenderness, "mild" = tenderness when touched, "moderate" = pain and flinching, "severe" = pain, flinching and withdrawal of the limb (where "severe" represents the worst possible degree of tenderness and "absent" is the best outcome).

Change in the rate of erythema of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline.The rates of "erythema" were specified as "absence", "presence", "impossible to evaluate".

Change in the rate of movement restrictions in the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. For the assessment, the categorical scale consistent with the Form for evaluation (Investigator's Assessment) of the restriction of movements was used. The rates of movement restrictions (amplitude of movements) were specified in the evaluation form as "1 - Normal range", "2 - Slightly limited range", " 3 - Moderately limited range" ,"4 - Severely limited range" and "5 - Joint movement is impossible " (where higher score means worse outcome).

Time to achieve the 50% decrease in pain intensity in the assessed joint relative to the baseline VAS level. VAS is a hard copy 100 mm scale with the indications: "Absence of pain" on the left side of the scale (0 mm point) and "The most severe pain ever experienced" on the right side of the scale (100 mm point)). The better outcome would be "Absence of pain", the worse outcome would be "The most severe pain ever experienced".

Time to use of the rescue medication was calculated as the time in hours from the date/time of administration (first dose) of the investigational product to the date/time of the first use of the rescue medication.

The proportion of patients who received the rescue medication within 72 hours of starting the investigational product therapy

The proportion of patients who received the rescue medication over the entire treatment period

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. (The result for each of the 8 categories ("Dressing and Grooming", "Arising", "Eating", "Walking", "Hygiene", "Reach", "Grip", "Activities") of the HAQ questionnaire was calculated as the maximum score of responses (on an ordinal scale from 0 (best) to 3 (worst): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3)) to questions included in this category. If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". The sum of points for the evaluated categories was calculated and divided by the number of categories, which gives a disability index in the range of 0 to 3.)

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2".

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2".

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2".

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2".

Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2".

Including area under the plasma concentration-time curve over the dosing interval (AUC0-tau)

Including Area under the active substance concentration-time curve from zero (before drug administration) to infinity (AUC0-∞)

Including Maximum concentration of the active substance (Cmax)

Including elimination constant (Kel)

Including Time to reach maximum concentration of the active substance (tmax)

Including terminal half-life (T 1/2)

Change in the serum rate of high-sensitive CRP (hs-CRP) in 24, 72 hours, on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug compared to baseline

Change in the rate of serum amyloid protein A in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of IL-1α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of IL-1β in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of IL-1RA in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of IL-6 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of IL-8 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline

Change in the serum rates of TNF-α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline