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

Plaque Psoriasis Clinical Trial

— INDUS-3  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04855721
• Other study ID #: AUR101-202
• Status: Completed
• Phase: Phase 2
• Start date: May 4, 2021
• Est. completion date: December 10, 2022

Study information

• Verified date: December 2022
• Source: Aurigene Discovery Technologies Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: December 10, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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. Static 5-point IGA modified [mod] 2011 scale of 3 or higher at screening and Day 1

4. Adult males or females, = 18 to = 70 years of age

5. Ability to communicate well with the investigator and to comply with the requirements of the entire study

6. 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. BMI < 18 or > 40

3. 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

4. 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.

5. Current treatment or history of treatment for psoriasis with other investigational or approved biological agents (e.g. anti-TNFa inhibitors - adalimumab, etanercept, infliximab, alefacept etc.) within 3 months prior to the first administration of study drug

6. 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.

7. 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.

8. 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)

9. Any surgery requiring general anesthesia within 3 months prior to screening

10. 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.

11. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at screening

12. Patient with known history of systemic tuberculosis or currently suspected or known to have active tuberculosis

13. Patient expected to be started on anti-tubercular therapy either for treatment or prophylaxis of tuberculosis

14. 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.

15. History of hypersensitivity or idiosyncratic reaction to any investigational ROR-gamma inhibitors or any of the excipients of study drug

16. History of alcohol or substance abuse that will affect compliance to study procedures/schedule as per Investigator opinion

17. 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

18. Positive pregnancy test for women of child-bearing potential (WOCBP) at the screening or randomization visit

19. Male patients who are sexually active with WOCBP, not willing to use reliable contraception methods as mentioned in section 8.14

20. 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

21. Has received any investigational biologic agents within 3 months or 5 half-lives (whichever is longer) prior to the first administration of study drug

22. 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

23. History of other auto-immune disorders (except psoriasis and psoriatic arthritis) where treatment with systemic immunosuppressants is required

24. 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

25. 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

26. 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

27. 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

28. 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

29. Patients who have received live attenuated vaccine in the 4 weeks prior to the first administration of study drug -

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis

Intervention

Drug:
• AUR101
Oral ROR-gamma inverse agonist
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Great Lakes Research Group, Inc	Bay City	Michigan
United States	Moore Clinical Research, Inc.	Brandon	Florida
United States	Skin Research Institute	Coral Gables	Florida
United States	Dermatology Treatment & Research Center	Dallas	Texas
United States	Accel Research Sites - Deland CRU	DeLand	Florida
United States	FXM Clinical Research Fort Lauderdale	Fort Lauderdale	Florida
United States	Johnson Dermatology	Fort Smith	Arkansas
United States	First OC Dermatology	Fountain Valley	California
United States	Abys New Generation Research Inc.	Hialeah	Florida
United States	Direct Helpers Research Center	Hialeah	Florida
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	Dermatology Research Associates	Los Angeles	California
United States	Floridian Reserach	Miami	Florida
United States	FXM Clinical Research Miami LLC	Miami	Florida
United States	FXM Clinical Research Miramar LLC	Miramar	Florida
United States	Sadick Research Group	New York	New York
United States	The Dermatology Specialists	New York	New York
United States	Paddington Testing Co, Inc	Philadelphia	Pennsylvania
United States	Northwest AR Clinical Trials Center	Rogers	Arkansas
United States	Medisearch Clinical Trials	Saint Joseph	Missouri
United States	University Clinical Trials, Inc.	San Diego	California
United States	Clinical Science Institute	Santa Monica	California
United States	Unison Clinical Trials	Sherman Oaks	California
United States	Lenus Research & Medical Group, LLC	Sweetwater	Florida
United States	Center for Clinical Studies Ltd., LLP.	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Aurigene Discovery Technologies Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Metabolite of AUR101 identification from plasma collected at week 4	AUR101 metabolites identification in plasma (currently the metabolites are unidentified and no more details are available)	Week 4
Other	Metabolite of AUR101 quantification from plasma collected at week 4	AUR101 metabolites quantification in plasma AUR101 (currently the metabolites are unidentified and no more details are available)	Week 4
Other	Metabolite of AUR101 identification from urine collected at week 4	AUR101 metabolites identification in urine (currently the metabolites are unidentified and no more details are available)	Week 4
Other	Metabolite of AUR101 quantification from urine collected at week 4	AUR101 metabolites quantification in urine (currently the metabolites are unidentified and no more details are available)	Week 4
Other	Proportion of patients achieving PASI 75 response	PASI-75; A higher proportion of patients reaching PASI-75 means betterment in higher proportion of patients	Week 16
Other	Proportion of patients achieving PASI 90 response	PASI-90; A higher proportion of patients reaching PASI-90 means betterment in higher proportion of patients	Week 16
Other	Proportion of patients achieving PASI 100 response	PASI-100; A higher proportion of patients reaching PASI-100 means betterment in higher proportion of patients	Week 16
Other	Proportion of patients achieving PASI 50 response	PASI-50; A higher proportion of patients reaching PASI-50 means betterment in higher proportion of patients	Week 16
Other	Proportion of patients achieving IGA 0 or 1 response	IGA 0 or 1; A higher proportion of patients reaching IGA 0 or 1 means betterment in higher proportion of patients	Week 16
Other	Proportion of patients achieving DLQI 0 or 1 score	DLQI 0 or 1; A higher proportion of patients reaching DLQI 0 or 1 means betterment in higher proportion of patients	Week 16
Other	Percent change from baseline in PASI score at week 16	Percent change from baseline	Week 16
Primary	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	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
Secondary	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
Secondary	Proportion of patients achieving IGA 0 or 1 at week 12	IGA (Investigator's Global Assessment); Lower scores are better	Week 12
Secondary	Percent change from baseline in PASI score at week 12	Percent Change in PASI from baseline	Week 12
Secondary	Percent change from baseline to week 12 in percent BSA involved	Percent Change in BSA (body surface area) from baseline	Week 12
Secondary	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
Secondary	Plasma Pharmacokinetic parameters at week 4	Cmax (maximum Plasma concentration)	Week 4
Secondary	Plasma Pharmacokinetic parameters at week 4	AUC0-8 (Area Under The Curve for 8 hours) after morning drug administration	Week 4
Secondary	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
Secondary	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
Secondary	Changes in Pulse Rate	Pulse Rate changes during trial	From Day 1 through Follow Up Visit at Week 14
Secondary	Changes in Temperature	Body temperature changes during trial	From Day 1 through Follow Up Visit at Week 14
Secondary	Changes in Respiratory Rate	Respiratory Rate changes during trial	From Day 1 through Follow Up Visit at Week 14
Secondary	Changes in PR interval in ECG (Electro Cardio Gram)	Changes in PR Interval	Week 14 (Follow Up Visit)
Secondary	Changes in QRS interval in ECG (Electro Cardio Gram)	Changes in QRS Interval	Week 14 (Follow Up Visit)
Secondary	Changes in QTc interval in ECG (Electro Cardio Gram)	Changes in QTc Interval	Week 14 (Follow Up Visit)
Secondary	Changes in CBC (Complete Blood Count)	Complete Blood Count (CBC)	From Day 1 through Follow Up Visit at Week 14
Secondary	Changes in Liver Function Tests	Liver Function Tests (AST, ALT, Total Bilirubin)	From Day 1 through Follow Up Visit at Week 14
Secondary	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