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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm-1 400 mg BID | Experimental | 400 mg AUR101 twice daily |
|
| Arm-2 600 mg BID | Experimental | 600 mg AUR101 twice daily |
|
| Arm-3 - Matching Placebo BID | Placebo Comparator | Matching Placebo twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AUR101 | Drug | Inhibitor of RORγ |
|
| 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 |
| 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. |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Shilendra Pandey, MSc | Aurigene Discovery Techologies Limited | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| B.J Medical College & Civil Hospital | Ahmedabad | Gujarat | 380016 | India | ||
| Kempegowda Institute of Medical Sciences |
Not yet planned to share
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90 patients were enrolled.. Out of these 90, 30 patients each were enrolled in 400 mg PO BID arm, 600 mg BID arm and placebo BID arm.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm-1 | 400 mg AUR101 twice daily AUR101: Inhibitor of RORγ |
| FG001 | Arm-2 | 600 mg AUR101 twice daily AUR101: Inhibitor of RORγ |
| FG002 | Arm-3 | Matching Placebo twice daily Matching Placebo: Drug-Placebo of AUR101 tablet |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm-1 | 400 mg AUR101 twice daily AUR101: Inhibitor of RORγ |
| BG001 | Arm-2 | 600 mg AUR101 twice daily AUR101: Inhibitor of RORγ |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | ITT Population | Posted | Count of Participants | Participants | week 12 |
|
From enrolment to 2 week follow up
No difference
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm-1 | 400 mg AUR101 twice daily AUR101: Inhibitor of RORγ | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 Infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pruritus | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Divyesh Mandavia | Aurigene Discovery Technologies Limited | 9427181182 | divyesh_m@aurigene.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 7, 2019 | Aug 23, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 25, 2021 | Aug 23, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Matching Placebo | Drug | Drug-Placebo of AUR101 tablet |
|
|
| 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 |
| Bangalore |
| Karnataka |
| 560004 |
| India |
| Sapthagiri Hospital | Bangalore | Karnataka | 560090 | India |
| Triveni Polyclinic | Nagpur | Maharashtra | 440008 | India |
| Shree Hospital and Critical Care Centre | Nagpur | Maharashtra | 440009 | India |
| NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital | Nagpur | Maharashtra | 440019 | India |
| Sujata Birla Hospital & Medical Research Center | Nashik | Maharashtra | 422101 | India |
| Apex Hospitals Private Limited | Jaipur | Rajasthan | 302017 | India |
| Life Line Diagnostic Centre Cum Nursing Home | Kolkata | West Bengal | 700016 | India |
| BG002 | Arm-3 | Matching Placebo twice daily Matching Placebo: Drug-Placebo of AUR101 tablet |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race is defined as "a category of humankind that shares certain distinctive physical traits." In this study, all pateints enrolled were of Indian descent | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Psoriasis Area and Severity Index (PASI) | PASI (Psoriasis Area and Severity Index) measures the intensity of redness, thickness, and scaling of the psoriasis is assessed as none (0), mild (1), moderate (2), severe (3), or very severe (4). The three intensity scores are added up for each of the four body regions to give subtotals A1, A2, A3, A4. Each subtotal is multiplied by the body surface area represented by that region. The percentage area affected by psoriasis is evaluated in the four regions of the body - Head and neck, Upper Limbs, Trunk and Lower Limbs. Minimum PASI Score is 0 and maximum is 72 | Mean | Standard Deviation | units on a scale |
|
| Arm-2 |
600 mg AUR101 twice daily AUR101: Inhibitor of RORγ |
| OG002 | Arm-3 | Matching Placebo twice daily Matching Placebo: Drug-Placebo of AUR101 tablet |
|
|
| Secondary | 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. | PASI-75 Response at Week 8 for ITT population | Posted | Count of Participants | Participants | Week 4 and Week 8 from study drug initiation for these secondary outcomes measures |
|
|
|
| Secondary | 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. | PASI-50 at week 12 | Posted | Count of Participants | Participants | Week 4, Week 8 and Week 12 |
|
|
|
| Secondary | 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 | ITT (Intention to Treat) population | Posted | Count of Participants | Participants | Week 4, Week 8 and Week 12 |
|
|
|
| Secondary | 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 | ITT Population | Posted | Mean | Standard Deviation | Percent change from baseline in PASI | week 4,8 and 12 |
|
|
|
| Secondary | 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. | ITT population | Posted | Mean | Standard Deviation | % decrease in IGA score | week 4,8 and 12 |
|
|
|
| Secondary | 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 | ITT Population | Posted | Mean | Standard Deviation | % decrease in BSA (Body Surface Area) | week 4,8 and 12 |
|
|
|
| Secondary | 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 | ITT Population | Posted | Mean | Standard Deviation | Percent change from baseline in DLQI | Week 4,8 and 12 |
|
|
|
|
| 30 |
| 0 |
| 30 |
| 2 |
| 30 |
| EG001 | Arm-2 | 600 mg AUR101 twice daily AUR101: Inhibitor of RORγ | 0 | 30 | 0 | 30 | 3 | 30 |
| EG002 | Arm-3 | Matching Placebo twice daily Matching Placebo: Drug-Placebo of AUR101 tablet | 0 | 30 | 2 | 30 | 1 | 30 |
| Psoriatic Erythroderma | Immune system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Depressed Mood | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
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|
| Title | Measurements |
|---|---|
|
| PASI-50 at Week 4 |
|
|
| IGA Response of 0 or 1 at Week 4 |
|
|
| Percent Change in PASI at week 4 |
|
|
| Percent Change from baseline in IGA at week 4 |
|
|
| BSA % Change at Week 4 |
|
|
| Percent Change from Baseline in DLQI score at week 4 |
|