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

Phase 2

Completed

• Conditions: Chronic Plaque-type Psoriasis
• Interventions: Drug: AUR101; Drug: Matching Placebo

• Registration Number: NCT04207801
• Lead Sponsor: Aurigene Discovery Technologies Limited

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-12-19
• Study First Submitted QC: 2019-12-19
• Study First Posted: 2019-12-23
• Study Start: 2020-01-21
• Primary Completion: 2021-03-20
• Study Completion: 2021-04-15
• Results First Submitted: 2022-08-23
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-20
• Last Update Submitted: 2023-07-20
• Results First Posted: 2023-08-14
• Last Update Posted: 2023-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm-1 400 mg BID	AUR101	400 mg AUR101 twice daily
Arm-2 600 mg BID	AUR101	600 mg AUR101 twice daily
Arm-3 - Matching Placebo BID	Matching Placebo	Matching Placebo twice daily

Primary Outcome Measures

Name	Time	Method
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))	week 12	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

Secondary Outcome Measures

Name	Time	Method
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))	Week 4 and Week 8 from study drug initiation for these secondary outcomes measures	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.
Proportion of Patients Achieving Investigator Global Assessment (IGA) Score of 0 or 1	Week 4, Week 8 and Week 12	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
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))	Week 4, Week 8 and Week 12	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.
Change From Baseline in Dermatology Life Quality Index (DLQI)	Week 4,8 and 12	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
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score.	week 4,8 and 12	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
Change From Baseline in Investigator Global Assessment (IGA) Scale	week 4,8 and 12	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.
Change From Baseline to Week 4, 8 and 12 in Percent Body Surface Area (BSA) Involved	week 4,8 and 12	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

Trial Locations

Locations (9)

Kempegowda Institute of Medical Sciences; 🇮🇳 Bangalore, Karnataka, India

Sapthagiri Hospital; 🇮🇳 Bangalore, Karnataka, India

B.J Medical College & Civil Hospital; 🇮🇳 Ahmedabad, Gujarat, India

Apex Hospitals Private Limited; 🇮🇳 Jaipur, Rajasthan, India

Life Line Diagnostic Centre Cum Nursing Home; 🇮🇳 Kolkata, West Bengal, India

NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital; 🇮🇳 Nagpur, Maharashtra, India

Triveni Polyclinic; 🇮🇳 Nagpur, Maharashtra, India

Shree Hospital and Critical Care Centre; 🇮🇳 Nagpur, Maharashtra, India

Sujata Birla Hospital & Medical Research Center; 🇮🇳 Nashik, Maharashtra, India