ESK-001 for Safety and Tolerability

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Alumis Inc

Disqualifiers: Prior ESK-001 exposure, hypersensitivity, others

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ESK-001, to determine its safety and tolerability in healthy individuals. Researchers aim to understand how the drug behaves in the body over time. Participants will receive either ESK-001 or a placebo (a substance with no active drug) for comparison. The trial seeks healthy individuals without previous exposure to ESK-001 and no allergies to its ingredients. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for healthy participants, it might imply that participants should not be on any regular medications. Please check with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ESK-001, a pill, is generally safe and well-tolerated in healthy individuals. Studies have found that the body absorbs and eliminates it steadily. Reports from earlier trials suggest that most participants did not experience serious side effects, and any reactions were manageable. Additionally, ESK-001 is undergoing tests for other conditions, which increases researchers' confidence in its safety. The drug remains under study to ensure its continued safety for broader use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for various conditions, which often target symptoms or secondary pathways, ESK-001 is unique because it targets a novel mechanism of action directly linked to the underlying cause of the condition. Researchers are particularly excited about ESK-001 due to its innovative approach, potentially offering more effective management with fewer side effects. Additionally, the new active ingredient in ESK-001 could provide a groundbreaking alternative for patients who do not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective?

Research has shown that ESK-001, which participants in this trial may receive, could help treat certain conditions. In studies with patients, a high dose of ESK-001 led most participants to experience significant skin improvement, known as PASI 75, after 28 weeks. This suggests the drug might effectively manage symptoms for skin-related issues. Additionally, ESK-001 proved safe and well-tolerated in healthy participants, behaving predictably in the body. This drug targets a specific enzyme in the immune system, which may help control inflammation. Overall, early findings support its potential effectiveness. ^{2 4 6 7 8}

Who Is on the Research Team?

Mark Bradley

Principal Investigator

Alumis Inc

Are You a Good Fit for This Trial?

Inclusion Criteria

Participant is healthy as determined by medical history, physical examination, vital signs, and routine laboratory parameters

Other inclusions as specified in the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ESK-001 or placebo for 14 days to assess safety, tolerability, pharmacokinetics, and pharmacodynamics

2 weeks

Daily visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ESK-001
• Placebo

How Is the Trial Designed?

Group I: Experimental Drug ESK-001 Experimental Treatment 1 Intervention

Experimental Drug ESK-001

Group II: Placebo Placebo Group 1 Intervention

Placebo for ESK-001

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Published Research Related to This Trial

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

The review of clinical research data from 1977 to 2011 highlights significant inconsistencies in how adverse reactions (AR) to drugs are assessed, which can affect the reliability of safety information provided to patients.

To improve the safety profiles of medications, the authors advocate for the establishment of a common European standard for the structured assessment of adverse reactions in clinical research, as no such standard currently exists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessing adverse reactions in clinical trials]. Harnisch, S., Schade-Brittinger, C., Rief, W.[2013]

Safety pharmacology (SP) is crucial in drug development, helping to identify potential adverse effects of new chemical entities (NCEs) before they reach clinical trials, as outlined in ICH S7A and S7B guidelines.

Emerging practices in SP, such as frontloading and the use of biomarkers, can improve the assessment of drug safety by providing deeper mechanistic insights into potential adverse effects on major organ systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety pharmacology--current and emerging concepts. Hamdam, J., Sethu, S., Smith, T., et al.[2022]

In a review of 113 placebo-controlled randomized clinical trials published in 2016, only 19.5% of journal articles and 45.1% of study protocols provided descriptions of placebo contents, highlighting a significant lack of transparency in clinical trial reporting.

None of the journal publications explained the rationale for the choice of placebo ingredients, which raises concerns about the potential effects of active placebos on trial outcomes and complicates the assessment of the safety and efficacy of experimental interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals. Hong, K., Rowhani-Farid, A., Doshi, P.[2023]

Citations

1. investors.alumis.com investors.alumis.com/news-releases/news-release-details/late-breaking-esk-001-phase-2-ole-data-presented-2025-aad-annual?mobile=1&mobile=1

Late-Breaking ESK-001 Phase 2 OLE Data Presented at 2025 ... These data demonstrated that patients receiving 40 mg twice daily dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11602527/

Safety, tolerability, pharmacokinetics, and ... ESK‐001 was generally safe and well‐tolerated in healthy participants, showed linear dose‐dependent PK characteristics, and maximally inhibited TYK2‐dependent ...

3. investors.alumis.com investors.alumis.com/news-releases/news-release-details/late-breaking-data-eadv-esk-001-oral-tyk2-inhibitor-treatment?mobile=1&mobile=1

Late-Breaking Data at EADV of ESK-001, an Oral TYK2 ... 28-week data show ESK-001 was generally well tolerated and most patients treated with the top dose of 40 mg twice daily achieved PASI 75

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-esk-001-for-adults-with-systemic-lupus-erythematosus/

Study on the Safety and Effectiveness of ESK-001 for ... This study assesses the safety and effectiveness of the medication ESK-001 in treating adult patients with Systemic Lupus Erythematosus, ...

5. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2022-002633-34/CZ

Clinical Trials Register A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ESK-001 in Patients with Moderate to Severe Plaque ...

6. alumis.com alumis.com/file.cfm/18/docs/alumis_pub_2_for_website_aad_pres_vf.pdf

Efficacy and Safety of ESK-001, a Highly Selective Oral ... Efficacy and Safety of ESK-001, a Highly Selective Oral TYK2. Inhibitor ... Safety data displayed based on 8 December 2023 data cut of ongoing OLE study.

7. alumis.com alumis.com/file.cfm/18/docs/aad2025_pstr_ethnobridging_final.pdf

Pharmacokinetics, Safety, and Tolerability of ESK-001, an ... ESK-001, an oral TYK2 inhibitor, showed similar PK profiles across ethnicities with rapid absorption and steady elimination. Plasma exposures ...

8. researchgate.net researchgate.net/publication/386182509_Safety_tolerability_pharmacokinetics_and_pharmacodynamics_of_the_oral_allosteric_TYK2_inhibitor_ESK-001_using_a_randomized_double-blind_placebo-controlled_study_design

(PDF) Safety, tolerability, pharmacokinetics, and ... TRANSLATIONAL SCIENCE? Being well- tolerated and exhibiting clear PK/PD characteristics, ESK- 001 offers. further clinical development as ...