BI 730357 / Boehringer Ingelheim - LARVOL DELTA

Differential Effects of RORγ Inhibition on Selected Pathways in Plaque Psoriasis. (PubMed, J Invest Dermatol) - No abstract available

Journal • Dermatology • Immunology • Psoriasis

Revisiting RORγt Inhibition in Plaque Psoriasis: Lessons Learned from BI 730357. (PubMed, J Invest Dermatol) - No abstract available

Journal • Dermatology • Immunology • Inflammation • Psoriasis

Assessing Drug-Drug Interaction and Food Effect for BCS Class 2 Compound BI 730357 (Retinoic Acid-Related Orphan Receptor Gamma Antagonist, Bevurogant) Using a Physiology-Based Pharmacokinetics Modeling (PBPK) Approach with Semi-Mechanistic Absorption. (PubMed, Pharmaceutics) - " The model accurately predicted an observed itraconazole drug-drug interaction (DDI) in fasted subjects and was used to explore the effects of the strong CYP3A4 inducer rifampicin on the pharmacokinetics of BI 730357 after administration in fed subjects. The combined results suggest that the BI 730357 PBPK model with semi-mechanistic absorption can prospectively explore the effects of CYP3A4 inhibitors and inducers on the pharmacokinetics after administration in fed or fasted subjects within the given dose range."

Journal • PK/PD data

Phase II Randomized Trial of BI 730357, a Novel Oral RORγt Inhibitor, for Moderate-to-Severe Plaque Psoriasis. (PubMed, J Invest Dermatol) - "BI 730357 was well-tolerated with moderate efficacy versus placebo in plaque reduction."

Journal • P2 data • Dermatology • Immunology • Inflammation • Psoriasis

The Effect of BI 730357 (Retinoic Acid-Related Orphan Receptor Gamma t Antagonist, Bevurogant) on the Pharmacokinetics of a Transporter Probe Cocktail, Including Digoxin, Furosemide, Metformin, and Rosuvastatin: An Open-Label, Non-randomized, 2-Period Fixed-Sequence Trial in Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "BI 730357 was safe and well tolerated. This trial confirms the usefulness and tolerability of the transporter cocktail consisting of digoxin, furosemide, metformin, and rosuvastatin in assessing drug-transporter interactions in vivo."

Journal • PK/PD data • Breast Cancer • Oncology • Solid Tumor

Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The maximum drug effect was largest for patients with no prior biologic use, smaller for patients with prior use of non-interleukin-17 inhibitors, and smallest for patients with prior interleukin-17 inhibitor use. The models allowed robust simulation of large patient populations, predicting a plateau in PASI outcomes for BI 730357 exposure above 2,000 nmol/L."

Journal • Dermatology • Immunology • Psoriasis • CRP • IL17A

A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is (clinicaltrials.gov) - P2 | N=165 | Terminated | Sponsor: Boehringer Ingelheim | Completed ➔ Terminated; Due to company decision.

Trial termination • Dermatology • Immunology • Psoriasis

A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is (clinicaltrials.gov) - P2; N=165; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis

Retinoic acid-related orphan receptor gamma (RORγ) inverse agonists/antagonists for the treatment of inflammatory diseases - where are we presently? (PubMed, Expert Opin Drug Discov) - "The main reasons were lack of efficacy (topical) or safety signals (oral) as well as, amongst other things, thymic lymphomas as seen with BMS-986251 in a preclinical study and liver enzyme elevations in humans with VTP-43742. Possibilities to mitigate these risks could be the use of RORγt inverse agonists with different chemical structures not interfering with thymocytes maturation and no liver tox inducing properties. With few new frontrunners (e.g. ABBV-157 (cedirogant), BI 730357 or IMU-935) this is still an exciting time for this novel treatment approach."

Journal • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Oncology • IL17A

A Study to Test Different Doses of BI 730357 and Find Out Whether They Reduce Symptoms in People With Active Psoriatic Arthritis (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Boehringer Ingelheim; N=160 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

This Study is Done in Patients With Plaque Psoriasis and Tests How Well They Tolerate BI 730357 and How Effective it is (clinicaltrials.gov) - P2; N=274; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis • Psoriatic Arthritis

A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is (clinicaltrials.gov) - P2; N=165; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting; Trial completion date: Feb 2027 ➔ Jul 2021; Trial primary completion date: Jan 2027 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Clinical • Trial completion

This Study is Done in Patients With Plaque Psoriasis and Tests How Well They Tolerate BI 730357 and How Effective it is (clinicaltrials.gov) - P2; N=270; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Dermatology • Immunology • Psoriasis • Psoriatic Arthritis

A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood (clinicaltrials.gov) - P1; N=16; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Discovery of a Series of Pyrazinone RORγ Antagonists and Identification of the Clinical Candidate BI 730357. (PubMed, ACS Med Chem Lett) - "The series offers attractive potency and selectivity in combination with favorable druglike properties, such as metabolic stability and aqueous solubility. Lead optimization identified a clinical candidate, compound (S)-11 (BI 730357), for the treatment of autoimmune diseases."

Clinical • Journal • Immunology • IL17A

A Study in Healthy People to Test Whether BI 730357 Affects How 4 Other Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Taken up in the Body (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study to Test Different Doses of BI 730357 and Find Out Whether They Reduce Symptoms in People With Active Psoriatic Arthritis (clinicaltrials.gov) - P2; N=160; Not yet recruiting; Sponsor: Boehringer Ingelheim

Clinical • New P2 trial • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: Boehringer Ingelheim; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Boehringer Ingelheim

Clinical • New P1 trial

A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: Boehringer Ingelheim; N=270 ➔ 180

Clinical • Enrollment change • Dermatology • Immunology • Psoriasis

A trial to test whether BI 730357 is effective in patients with active ankylosing spondylitis A BI 730357 hatékonyságára irányuló vizsgálat aktív Bechterew-kórban szenvedő betegek körében (clinicaltrialsregister.eu) - P2; N=40; Ongoing; Sponsor: Boehringer Ingelheim RCV GmbH & Co KG

Clinical • New P2 trial • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis

A Study in Healthy People to Test Whether BI 730357 Affects How 4 Other Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Taken up in the Body (clinicaltrials.gov) - P1; N=15; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Boehringer Ingelheim; Trial completion date: Aug 2025 ➔ Feb 2027; Trial primary completion date: Jul 2025 ➔ Jan 2027

Clinical • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

A Study in Healthy People to Test Whether BI 730357 Affects How 4 Other Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Taken up in the Body (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: Boehringer Ingelheim; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open