A Dose-Ranging Phase II Study of AUR101 in Psoriasis (INDUS-3)

Study Overview
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Brief Summary
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A Phase II, Multicenter, Double-blind, Double-dummy, Placebo controlled, Randomized Study to Evaluate the Efficacy and Safety of AUR101 in patients with Moderate-to-Severe Psoriasis (INDUS-3)

Detailed Description
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This will be a multicenter, double-blind, double-dummy, placebo controlled, randomized study to evaluate the efficacy and safety of AUR101 in patients with moderate-to-severe psoriasis. Approximately 128 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 four groups (three dose groups of AUR101 and one placebo group) in the ratio of 1:1:1:1. The patients in each arm will receive AUR101 of 200 mg twice daily, 400 mg twice daily, 400 mg once daily or matching placebo for 16 weeks in a double blind, double dummy fashion. All patients will be followed up for 14 ± 2 days of their last dose for safety 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 AUR101 in Patients With Moderate-to-Severe Psoriasis (INDUS-3)

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: AUR101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of chronic plaque-type psoriasis, diagnosed at least 6 months before screening Psoriasis of at least moderate severity, defined as PASI≥12 and involved BSA≥10 % at screening and Day 1 Static 5-point IGA modified [mod] 2011 scale of 3 or higher at screening and Day 1 Adult males or females, ≥ 18 to ≤ 70 years of age Ability to communicate well with the investigator and to comply with the requirements of the entire study 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: History of erythrodermic, guttate or pustular psoriasis within last 12 months BMI < 18 or > 40 History of lack of response to ustekinumab, secukinumab or ixekizumab (or any therapeutic agent targeted to IL12, IL-17 or IL-23) at approved doses after at least 3 months of therapy Current treatment or history of treatment for psoriasis with any investigational or approved IL-17, IL-12 or IL-23 antagonist biological agents (e.g. secukinumab, briakinumab, tildrakizumab, ustekinumab etc.) within 6 months prior to the first administration of study drug. Current treatment or history of treatment for psoriasis with other investigational or approved biological agents (e.g. anti-TNFα inhibitors - adalimumab, etanercept, infliximab, alefacept etc.) within 3 months prior to the first administration of study drug Current treatment or history of treatment for psoriasis with non-biological systemic medications or immunomodulators (including systemic steroids, apremilast, methotrexate, cyclosporine, acitretin, etc.) or phototherapy within 4 weeks prior to the first administration of study drug. Treatment with medicated topical agents (having active pharmaceutical ingredient that can impact or interfere with the effect of the study drug) within 2 weeks prior to the first administration of study drug. Evidence of organ dysfunction (e.g. liver dysfunction ≥ 1.5 X of ULN for ALT, AST or ALP or Total Bilirubin, or renal dysfunction of ≥ 1.5X of ULN of serum creatinine) Any surgery requiring general anesthesia within 3 months prior to screening History of malignancy within last 5 years except patients with non-melanoma skin cancer or carcinoma in situ of cervix who can participate in the study. Adequately treated cutaneous basal or squamous cell carcinoma are allowed. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at screening Patient with known history of systemic tuberculosis or currently suspected or known to have active tuberculosis Patient expected to be started on anti-tubercular therapy either for treatment or prophylaxis of tuberculosis Suspected tuberculosis infection as evident from a positive QuantiFERON TB-Gold test (QFT) or Mantoux test (MT) at screening. Patients with a positive QFT or MT may participate in the study if further work up as per the opinion of the investigator (like Chest X-ray or CT scan of Chest or other locally acceptable method for diagnosing active tuberculosis) establishes that patient does not have active tuberculosis. Patients with latent tuberculosis should not be enrolled except when they are not planned to start prophylaxis for tuberculosis during the study period. History of hypersensitivity or idiosyncratic reaction to any investigational ROR-gamma inhibitors or any of the excipients of study drug History of alcohol or substance abuse that will affect compliance to study procedures/schedule as per Investigator opinion Any previous gastrointestinal surgery or recent (within 3 months) / current history of gastrointestinal disease, that in the opinion of investigator, could impact the absorption of the study drug Positive pregnancy test for women of child-bearing potential (WOCBP) at the screening or randomization visit Male patients who are sexually active with WOCBP, not willing to use reliable contraception methods as mentioned in section 8.14 Lactating women or WOCBP who are neither surgically sterilized nor willing to use reliable contraceptive methods (hormonal contraceptive, IUD or any double combination of male or female condom, spermicidal gel, diaphragm, sponge, cervical cap). Please see section 8.14 for acceptable contraceptive practices Has received any investigational biologic agents within 3 months or 5 half-lives (whichever is longer) prior to the first administration of study drug Has received another new chemical entity/non-biologic investigational drug within 28 days or 5 half-lives of investigational drug (whichever is longer) prior to study day 1 History of other auto-immune disorders (except psoriasis and psoriatic arthritis) where treatment with systemic immunosuppressants is required History of active infection and/or febrile illness within 7 days prior to Day 1. The infection adequately treated by antibiotics during the screening period as per investigator opinion will be allowed to undergo randomization, provided patient is stable for at least 7 days before randomization Current swab-positive or suspected (under investigation) Covid-19 infection or fever and other signs or symptoms suggestive of Covid-19 infection with recent contact of person(s) with confirmed Covid-19 infection, at screening or Day 1 History or presence of any major medical illness (e.g. renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, or local active infection/infectious illness) or psychiatric disease, or clinically significant laboratory / ECG abnormalities at screening, any or a combination of illnesses, which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study History of any unstable cardiac (including Class III or IV congestive heart failure by New York Heart Association Criteria), respiratory, hepatic, renal or other systemic conditions within 3 months prior to first study drug administration Use of herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of study drug Patients who have received live attenuated vaccine in the 4 weeks prior to the first administration of study drug -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: There are 4 groups in the study; 1 with placebo and 3 with different AUR101 dosing regimens
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AUR101 400 mg PO BID<br>Patients will receive AUR101 / placebo in double blind, double dummy manner | Drug: AUR101<br>* Oral ROR-gamma inverse agonist<br>|
| Experimental: AUR101 200 mg PO BID<br>Patients will receive AUR101 / placebo in double blind, double dummy manner | Drug: AUR101<br>* Oral ROR-gamma inverse agonist<br>|
| Experimental: AUR101 400 mg PO QD<br>Patients will receive AUR101 / placebo in double blind, double dummy manner | Drug: AUR101<br>* Oral ROR-gamma inverse agonist<br>|
| Placebo Comparator: Placebo<br>Patients will receive AUR101 / placebo in double blind, double dummy manner | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving PASI 75 response (i.e. 75 percent reduction from baseline PASI [Psoriasis Area and Severity Index] score) at the end of week 12. | PASI-75; A higher proportion of patients reaching PASI-75 means betterment in higher proportion of patients | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving PASI 75 response (i.e. 75 percent reduction from baseline PASI [Psoriasis Area and Severity Index] score) at the end of week 4 and 8 | PASI-75; A higher proportion of patients reaching PASI-75 means betterment in higher proportion of patients | Week 4 and Week 8 | 
| Proportion of patients achieving PASI 50, PASI 90 and PASI 100 response at week 12. | PASI-50, PASI-90, PASI-100; A higher proportion of patients reaching PASI-50, PASI-90 or PASI-100 means betterment in higher proportion of patients | Week 12 | 
| Proportion of patients achieving IGA 0 or 1 at week 12 | IGA (Investigator's Global Assessment); Lower scores are better | Week 12 | 
| Percent change from baseline in PASI score at week 12 | Percent Change in PASI from baseline | Week 12 | 
| Percent change from baseline to week 12 in percent BSA involved | Percent Change in BSA (body surface area) from baseline | Week 12 | 
| Proportion of patients achieving DLQI score of 0 or 1 at week 12 | DLQI (Dermatology Life Quality Index) Score; Lower scores are better; Maximum score of 30 and minimum of 0 | Week 12 | 
| Plasma Pharmacokinetic parameters at week 4 | Cmax (maximum Plasma concentration) | Week 4 | 
| Plasma Pharmacokinetic parameters at week 4 | AUC0-8 (Area Under The Curve for 8 hours) after morning drug administration | Week 4 | 
| Nature and incidence of Treatment Emergent Adverse Events (TEAEs) | All Adverse Events which occur from the administration of study drug | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in Blood Pressure | Both systolic and diastolic Blood Pressure changes during trial will be measured | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in Pulse Rate | Pulse Rate changes during trial | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in Temperature | Body temperature changes during trial | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in Respiratory Rate | Respiratory Rate changes during trial | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in PR interval in ECG (Electro Cardio Gram) | Changes in PR Interval | Week 14 (Follow Up Visit) | 
| Changes in QRS interval in ECG (Electro Cardio Gram) | Changes in QRS Interval | Week 14 (Follow Up Visit) | 
| Changes in QTc interval in ECG (Electro Cardio Gram) | Changes in QTc Interval | Week 14 (Follow Up Visit) | 
| Changes in CBC (Complete Blood Count) | Complete Blood Count (CBC) | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in Liver Function Tests | Liver Function Tests (AST, ALT, Total Bilirubin) | From Day 1 through Follow Up Visit at Week 14 | 
| Changes in weight | Weight (in pounds) will be measured at all visits and change in weight (in pounds) will be presented | From Day 1 through Follow Up Visit at Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, AUR101, ROR, RORgamma, RORgamma inverse agonist, RORgamma inhibitor