A Phase II Study to Evaluate Efficacy & Safety of AUR101 in Patients of Moderate-to-Severe Psoriasis

Study Overview
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Brief Summary
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This will be a multicenter, double-blind, double-dummy, placebo controlled, randomized study to evaluate efficacy and safety of AUR101 (RORgamma inhibitor) in patients with moderate-to-severe psoriasis. Approximately 90 patients with chronic moderate-to-severe plaque psoriasis will be randomized to the 2 dose groups of AUR101 and one group of Placebo. The patients will receive the treatment for 12 weeks.

Detailed Description
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This will be a multicenter, double-blind, double-dummy, placebo controlled, randomized study to evaluate efficacy and safety of two doses of AUR101 in patients with moderate-to-severe psoriasis. Approximately 90 patients with chronic moderate-to-severe plaque psoriasis (defined as Psoriasis Area and Severity Index (PASI) ≥12 and Body Surface Area (BSA) involved ≥10%) will be randomized to the 2 dose groups of AUR101 and placebo in the ratio of 1:1:1. The patients in each arm will receive AUR101 of 400 mg twice daily or AUR101 600 mg twice daily or matching placebo twice daily for 12 weeks in a double blind, double dummy fashion. Every patient will receive 12 weeks of treatment. All the patients will be followed up for 14 ± 2 days of their last dose for safety assessment. A subset of approximately 25 patients, who consent, will be asked to come for plasma PK assessment in week 4 of dosing. Efficacy evaluation will be done by PASI, DLQI and BSA assessment. Safety assessment will be done by AEs and regular lab assessment.

Official Title
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A Phase II, Multicenter, Double-blind, Double-dummy, Placebo Controlled, Randomized, Study to Evaluate the Efficacy and Safety of Two Doses of AUR101 in Patients With Moderate-to-Severe Psoriasis

Conditions
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Chronic Plaque-type Psoriasis

Intervention / Treatment
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* Drug: AUR101
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Confirmed diagnosis of chronic plaque-type psoriasis, diagnosed at least 6 months before screening 2. Psoriasis of at least moderate severity, defined as PASI≥12 and involved BSA≥10 % at screening and Day 1 3. Adult males or females,≥18 to ≤ 65 years of age. 4. Ability to communicate well with the investigator and to comply with the requirements of the entire study 5. Willingness to give written informed consent (prior to any study related procedures being performed) and ability to adhere to the study restrictions and assessments schedule. Exclusion Criteria: 1. History of erythrodermic, guttate, or pustular psoriasis within last 12 months 2. Efficacy failure on any biologic (e.g. interleukin (IL) -17 antibodies or anti-TNF agents) for the treatment of psoriasis. 3. Static 5-point IGA mod 2011 scale of 0 to 2 at screening or Day 1. 4. BMI ≥ 35 kg/m2 5. Current treatment or history of treatment for psoriasis with IL-17 or IL-12/23 antagonist biological agents within 6 months prior to study day 1 6. Current treatment or history of treatment for psoriasis with other biological agents within 3 months prior to study day 1. 7. Current treatment or history of treatment for psoriasis with non-biological systemic medications or phototherapy within 4 weeks prior to study day 1. 8. Treatment with medicated topical agents within 2 weeks prior to study day 1. 9. History or presence of any medical or psychiatric disease, or clinically significant laboratory at screening, 10. Evidence of organ dysfunction 11. Any major recent surgery history within 3 months prior to screening 12. Alcohol abuse or drug abuse 13. History of malignancy 14. Positive for HIV, Hepatitis B or Hepatitis C at screening. 15. Patient with known past history of systemic tuberculosis or currently suspected or known to have tuberculosis 16. Patient expected to be started on anti-tubercular therapy either for treatment or prophylaxis of tuberculosis. 17. Suspected tuberculosis infection as evident from a positive QuantiFERON TBGold test (QFT) at screening. Patients with a positive QFT test may participate in the study if further work up as per the opinion of the investigator . 18. History of hypersensitivity or idiosyncratic reaction to any investigational RORgamma inhibitors or any of the excipients of study drug 19. Past gastrointestinal surgery or recent (within 3 months) / current history of gastrointestinal disease. 20. Positive pregnancy test for women of child bearing potential (WOCBP) at the screening or randomization visit 21. Male patients with partners of childbearing potential not willing to use reliable contraception methods. 22. Pregnant or lactating women or WOCBP who are neither surgically sterilized nor willing to use reliable contraceptive methods 23. Has received another new chemical entity/investigational drug within 28 days or 5 half-lives of investigational drug prior to study day 1. 24. Use of herbal remedies, mega dose vitamins and minerals during the 2 weeks prior to the first administration of investigational product. 25. Patients who have received live or attenuated vaccine in the 4 weeks prior to study day 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm-1 400 mg BID<br>400 mg AUR101 twice daily | Drug: AUR101<br>* Inhibitor of RORγ<br>* Other names: No other names;|
| Experimental: Arm-2 600 mg BID<br>600 mg AUR101 twice daily | Drug: AUR101<br>* Inhibitor of RORγ<br>* Other names: No other names;|
| Placebo Comparator: Arm-3 - Matching Placebo BID<br>Matching Placebo twice daily | Drug: Matching Placebo<br>* Drug-Placebo of AUR101 tablet<br>* Other names: No other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving Psoriasis Area and Severity Index (PASI) 75 (i.e. 75% Reduction From Baseline PASI Score). (Scores Range From 0 (Minimum) to 30 (Maximum)) | Proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75 (i.e. 75% reduction from baseline PASI score). (Scores range from 0 (minimum) to 30 (maximum)); The PASI is a scoring system to evaluate the baseline and response of therapy in psoriasis. Regulators commonly accept PASI 75 for measuring primary response of psoriasis in patients with Psoriasis. PASI 75 is a binary outcome that indicates a 75% or greater improvement in PASI from baseline | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving Psoriasis Area and Severity Index (PASI) 75 (i.e. 75% Reduction From Baseline PASI Score). (Scores Range From 0 (Minimum) to 30 (Maximum)) | Proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75 (i.e. 75% reduction from baseline PASI score). (Scores range from 0 (minimum) to 30 (maximum)); The PASI is a scoring system to evaluate the baseline and response of therapy in psoriasis. PASI 75 is a binary outcome that indicates a 75% or greater improvement in PASI from baseline. These secondary measures are measured as Week 4 and Week 8 from the initiation of study drug therapy. | Week 4 and Week 8 from study drug initiation for these secondary outcomes measures | 
| Proportion of Patients Achieving Psoriasis Area and Severity Index (PASI) 50 (i.e. 50% Reduction From Baseline PASI Score). (Scores Range From 0 (Minimum) to 30 (Maximum)) | Proportion of patients achieving Psoriasis Area and Severity Index (PASI) 50 (i.e. 50% reduction from baseline PASI score). (Scores range from 0 (minimum) to 30 (maximum)); The PASI is a scoring system to evaluate baseline and response of therapy in psoriasis. Like PASI 75, the PASI-50 is a binary outcome that indicates a 50% or greater improvement in PASI from baseline. PASI-50 is measured at Week 4, Week 8 and Week 12, as part of this secondary outcome measure. | Week 4, Week 8 and Week 12 | 
| Proportion of Patients Achieving Investigator Global Assessment (IGA) Score of 0 or 1 | The proportion of patients achieving Investigator Global Assessment (IGA) score of 0 or 1 (Scores range from 0 (0 or 1 clear to mild) to 4 (severe)); The 5-point IGA has a more stringent definition for a score of 1 (almost clear); This secondary measure is measured at Week 4, Week 8 and Week 12. The sponsor has represented the proportion in % form by multiplying by 100. The sponsor has done that in CSR (Clinical Study Report) as well | Week 4, Week 8 and Week 12 | 
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score. | The Psoriasis Area Severity Index (PASI) is an index used to express the severity of psoriasis. It combines the severity (erythema, induration and desquamation) and percentage of affected area. Percent change from baseline in Psoriasis Area and Severity Index (PASI) score. The PASI is a widely used instrument in psoriasis trials that assesses and grades the severity of psoriatic lesions and the patient's response to treatment. It produces a numeric score ranging from 0 to 72. This outcome measures the percentage decrease in PASI from baseline at various pre-specified timepoints | week 4,8 and 12 | 
| Change From Baseline in Investigator Global Assessment (IGA) Scale | The 5-point IGA has a more stringent definition for a score of 1 (almost clear) compared with 6-point IGA/Physician's Global Assessment (PGA) tools used in previous trials of other biologics in moderate-to-severe psoriasis. The IGA 0/1 rate is considered robust, demonstrating a strong association with PASI 90. The results for the 5-point IGA are expected to show the same association. This endpoint measures the percent change from baseline in Investigator Global Assessment (IGA) scale (Scores range from 0 (0 or 1 clear to mild) to 4 (severe)) at pre-specified time points. | week 4,8 and 12 | 
| Change From Baseline to Week 4, 8 and 12 in Percent Body Surface Area (BSA) Involved | BSA assessment measures the total area of the body affected by psoriasis. The body surface area (BSA) of involvement is an important indicator during the evaluation of psoriasis severity. In this secondary outcome measure, the change from baseline to week 4, 8 and 12 in percent Body Surface Area (BSA) involved is measured | week 4,8 and 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) | The DLQI is a validated, 10-question, self-reported questionnaire to evaluate the patient's perception of the impact of psoriasis on their quality of life. The DLQI Scores range from 0 to 30, and higher scores indicate greater health-related quality-of-life impairment. The DLQI questionnaire is divided into 6 commonly identified categories and is rated on a 4-point scale. This secondary outcome measures the change from baseline to week 4, 8 and 12 in Dermatology Life Quality Index (DLQI) score. The minimum value is 0 and maximum is 4 | Week 4,8 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AUR101, Psoriasis