A Study to Assess the Safety, Efficacy and Tolerability of Oral DFD-29 Capsules for the Treatment of Rosacea (MVOR-2)

Study Overview
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Brief Summary
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This is a 16-week, multicenter, randomized, parallel-group, double-blind, controlled study. After assessing eligibility during a screening period of up to 30 days, approximately 320 subjects at least 18 years old who are diagnosed with moderate to severe papulopustular rosacea will be randomized in a 3:3:2 ratio to DFD-29 (40 mg), Doxycycline capsules 40 mg, or Placebo once daily for 16 weeks. Of the 320 subjects, approximately 160 subjects are planned to be enrolled at 15 sites in the US, while the remaining subjects are to be enrolled at 14 sites in the EU.

Detailed Description
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This is a 16-week, multicenter, randomized, parallel-group, double-blind, controlled study. After assessing eligibility during a screening period of up to 30 days, approximately 320 subjects at least 18 years old who are diagnosed with moderate to severe papulopustular rosacea will be randomized in a 3:3:2 ratio to DFD-29 (40 mg), Doxycycline capsules 40 mg, or Placebo once daily for 16 weeks. Subject visits are scheduled at Screening, Baseline (Day 1), and Weeks 2, 4, 8, 12, and 16. Clinical assessments of efficacy will be conducted based on Investigator's Global Assessment modified scale without erythema (IGA), Clinician's Erythema Assessment (CEA), and total inflammatory lesion count at Weeks 2, 4, 8, 12, and 16 compared to Baseline. Laboratory assessments of blood (hematology and biochemistry) and urine (routine tests) will be conducted at Screening and Week 16 (end of study [EOS] or early termination) to assess for any changes in the safety parameters. Other safety assessments include vital signs, physical examination, urine pregnancy tests (for females of childbearing potential), and collection of AE data. The impact of the treatment on the quality of life (QoL) of the subjects will be assessed using the rosacea-specific tool RosaQoL in addition to the Dermatology Life Quality Index (DLQI) at Baseline and Weeks 2, 4, 8, 12, and 16.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel-Group, Active and Placebo Controlled Study to Assess the Safety, Efficacy and Tolerability of Oral DFD-29 Extended Release Capsules for the Treatment of Inflammatory Lesions of Rosacea Over 16 Weeks

Conditions
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Papulopustular Rosacea

Intervention / Treatment
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* Drug: DFD-29
* Drug: Doxycycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female subjects aged 18 years and above. Subjects must be in good general health as determined by the investigator and supported by the medical history. Subjects must have a clinical diagnosis of papulopustular rosacea with IGA grade 3 (moderate) or IGA grade 4 (severe) at Baseline. Subjects must have 15 to 60 (both inclusive) inflammatory lesions (papules and pustules) of rosacea over the face at Baseline. Subjects must have not more than 2 nodules or cysts at Baseline. Key Exclusion Criteria: Female subjects who are pregnant or nursing or planning to become pregnant during the study. Male subjects whose female partner is planning to conceive a child. Clinically significant abnormal laboratory test results that, in the opinion of the investigator, would compromise the subject's safety or ability to participate in the trial. History of organ transplant requiring immunosuppression, HIV, or other immune compromised state. History of lupus-like syndrome, autoimmune hepatitis, vasculitis, or serum sickness. Any clinically significant condition or situation other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multinational, multicenter, randomized, parallel-group, double-blind, controlled study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DFD-29<br>DFD-29 (40 mg) extended release capsules | Drug: DFD-29<br>* DFD-29 (40 mg) extended release capsules<br>|
| Active Comparator: Doxycycline 40 mg<br>Doxycycline 40 mg modified release capsules | Drug: Doxycycline<br>* Doxycycline 40 mg capsules<br>|
| Placebo Comparator: Placebo<br>Placebo capsules matching DFD-29 | Drug: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment (IGA) Treatment Success Compared to Placebo. | Proportion of subjects with IGA (modified scale without erythema) 'treatment success' - Grade 0 or 1 at Week 16 with at least 2 grade reduction from Baseline to Week 16, in the DFD-29 group compared to Placebo. The IGA is a 5-point scale ranging from '0'-Clear to '4' Severe, in which lower scores indicate a better outcome. | Baseline to Week 16 | 
| Total Inflammatory Lesion Count Reduction Compared to Placebo. | Total inflammatory lesion count (sum of papules, pustules, and nodules) reduction from Baseline to Week 16, in the DFD-29 group compared to Placebo. | Baseline to Week 16. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Total Inflammatory Lesion Count Compared to Placebo. | Percentage Change in Total inflammatory lesion count (sum of papules, pustules, and nodules) from Baseline to Week 16, in the DFD-29 group compared to Placebo. | Baseline to Week 16. | 
| IGA Treatment Success Compared to Doxycycline. | Proportion of subjects with IGA treatment success at week 16 in the DFD-29 group compared to Doxycycline capsules 40 mg. The IGA is a 5-point scale ranging from '0'-Clear to '4' Severe, in which lower scores indicate a better outcome. | Baseline to Week 16. | 
| Total Inflammatory Lesion Count Reduction Compared to Doxycycline. | Total inflammatory lesion count reduction from Baseline to week 16 in the DFD-29 group compared to Doxycycline capsules 40 mg. | Baseline to Week 16. | 
| Clinician's Erythema Assessment (CEA) Change Compared to Placebo. | Proportion of subjects with at least 2-grade reduction in CEA score from Baseline to Week 16 in the DFD-29 group compared to Placebo. The CEA is a 5-point scale ranging from '0' - No Redness to '4' - Fiery Redness, in which lower scores indicate a better outcome. | Baseline to Week 16. | 
| Change in Dermatology Life Quality Index (DLQI) Score Compared to Placebo. | Change in DLQI score from Baseline to Week 16 in the DFD-29 group compared to Placebo. The DLQI is a questionnaire with 10 questions. Each question is scored from 0 to 3. The total score can range from 0 to 30, where 0 means no impact of the disease on quality of life and 30 means maximum impact. Lower scores indicate better outcomes. | Baseline to Week 16. |