EAST-1 (ERAP-inhibition in Axial Spondyloarthritis Trial - 1)

NCT07047703 | Recruiting Phase 1

• 1 other identifier: GRWD0715-AS-01
• Study Type: interventional
• Target: 141
• Locations: 6 countries
• Sites: 14

Brief Summary

GRWD0715 is an orally administered, selective inhibitor of the Endoplasmic Reticulum Aminopeptidase 1 \[ERAP1\] enzyme being explored as a potential new treatment for axial spondyloarthritis (axSpA), a long term condition caused by inflammation predominantly affecting the sacroiliac joints (SIJs) and spine.

Conditions

Axial Spondyloarthritis (AxSpA)

Keywords

Axial Spondyloarthritis; AxSpA

Outcome Measures

Primary Outcomes (5)

• Incidence and nature of dose limiting event(s) (DLE)s (Parts A and B only)

  To determine safety and tolerability of GRWD0715 in healthy volunteers (Part A) and participants with axSpA (Part B)

  From first dose to 15 days post last dose of study drug

• Incidence, Type and Severity of treatment related adverse events (TRAEs)

  To determine safety and tolerability of GRWD0715 in healthy volunteers (Part A) and participants with axSpA (Parts B and C)

  From first dose to 15 days post last dose of study drug

• Incidence, type and severity of treatment emergent adverse events (TEAEs)

  To determine safety and tolerability of GRWD0715 in healthy volunteers (Part A) and participants with axSpA (Parts B and C)

  From first dose to 15 days post last dose of study drug

• To determine the efficacy of GRWD0715 compared to placebo in participants with axSpA (Part D)

  Analysis of the Assessment of Spondyloarthritis International Society (ASAS) Core Outcome Set (COS). ASAS20 (improvement of 20% or more and 1 unit or more; improvement in at least 3 of 4 domains; no worsening on fourth dimension) and ASAS40 (improvement of 40% and 2 units or more; improvement in at least 3 of 4 domains; no worsening on fourth dimension) will be calculated from constituent questions with the ASAS COS clinical measures and patient reported outcomes

  From baseline/Day 1 to Week 12

• Analysis of SPARCC MRI activity of the SIJs (sacroiliac joints) and spine

  To determine the efficacy of GRWD0715 compared to placebo in participants with axSpA (Part D)

  From baseline/Day 1 to Week 12

Secondary Outcomes (9)

• PK Parameter Trough Concentrations

  From Day 1 to Day 4 (Part A) / Day 35 (Part B) / Week 12 (Parts C and D)

• PK Parameter Cmax (Maximum observed concentration)

  From Day 1 to Day 4 (Part A) / Day 35 (Part B)

• PK Parameter Tmax (Time to maximum observed concentration)

  From Day 1 to Day 4 (Part A) / Day 35 (Part B)

• PK Parameter AUC0-t (Area under the concentration-time curve)

  From Day 1 to Day 4 (Part A) / Day 35 (Part B)

• PK Parameter T1/2 (Half life)

  From Day 1 to Day 4 (Part A) / Day 35 (Part B)

Study Arms (4)

Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers

EXPERIMENTAL

Drug: Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers

Part B - Multiple Ascending Dose (MAD) in participants with axSpA

EXPERIMENTAL

Drug: Part B - Multiple Ascending Dose (MAD) in participants with axSpA

Part C - Safety expansion cohort in participants with axSpA

EXPERIMENTAL

Drug: Part C - Safety expansion cohort in participants with axSpA

Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA

EXPERIMENTAL

Drug: Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA

Interventions

Part B - Multiple Ascending Dose (MAD) in participants with axSpA DRUG

Participants in Part B will receive GRWD0715 for 28 days

Part B - Multiple Ascending Dose (MAD) in participants with axSpA

Part C - Safety expansion cohort in participants with axSpA DRUG

Participants in Part C will receive GRWD0715 for 12 weeks

Part C - Safety expansion cohort in participants with axSpA

Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers DRUG

Participants in Part A will receive a single dose of GRWD0715 on Day 1 only.

Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers

Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA DRUG

Participants in Part D will receive GRWD0715 or placebo-to-match for 12 weeks

Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers
• Healthy male and female subjects aged 18-55 years inclusive, at the Screening visit
• Participant must provide written informed consent to participate in the study
• Male participants (and their female partners) / female participants must be willing to adhere to contraception requirements as detailed in the protocol
• Non-smokers or ex-smokers who have not smoked within the previous 6 months, as determined at the Screening visit
• Participant with a Body Mass Index (BMI) of 19-30. Body Mass Index = Body weight (kg) / \[Height (m)\]2
• AxSpA Participants
• Male or female, 18-65 years of age
• Participants diagnosed with Axial Spondyloarthritis, also fulfilling ASAS classification criteria including:
• HLA-B27 +ve (local testing)
• Objective evidence of inflammation at screening, specifically active sacroiliac joint inflammation on MRI fulfilling the ASAS MRI criteria (MRI+), assessed by the Principal Investigator or appropriately trained delegate, and/or elevated C-reactive protein (CRP+) ≥5.0mg/L.
• Symptom duration of ≥3 months
• Age at onset of active disease of \<40 years
• A score of ≥ 2.1 on the Ankylosing Spondylitis Disease Activity Score (ASDAS) on current treatment.
• At least one of the following:

You may not qualify if:

• Healthy Volunteers
• Participation in a New Chemical Entity clinical study within the previous 124 days or a marketed drug clinical study within the previous 93 days
• Known infection or lifestyle risk factors for human immunodeficiency virus (HIV) and/or hepatitis B or C infection, as determined at the Screening visit
• AxSpA Participants
• Participants who have received \>1/(Australia only) \>2 biologic or JAK inhibitor DMARD or are receiving any other disease-modifying antirheumatic drugs (other than those allowed), thalidomide (including previous use) and other prohibited concomitant medications.
• Inadequate Haematologic function, defined as:
• Haemoglobin \<10 g/dL.
• Absolute white blood cell count \<3.0 x 109 /L (\<3000 mm3)
• Absolute neutrophil count \<1.2 x 109 /L (\<1200 mm3)
• Absolute lymphocyte count \<1.0 x 109 /L (\<1000 mm3)
• Platelet count \<100 x 109 /L (\<100.000 mm3)
• Inadequate liver function, defined as; total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal at screening visit. For subjects with Gilberts syndrome, upper limit of normal for total bilirubin will be 2.9mg/dl
• History of any other autoimmune rheumatic disease (e.g., psoriatic arthropathy, systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymositis) or known diagnosis of fibromyalgia
• Participants with a previous history of or currently stable psoriasis are eligible
• Active or symptomatic inflammatory bowel disease (IBD). Participants with a history of IBD are allowed to participate

Sponsors & Collaborators

• Grey Wolf Therapeutics: lead

Study Sites (14)

University of the Sunshine Coast (UniSC)

Birtinya, Australia

RECRUITING

University of the Sunshine Coast (UniSC)

Morayfield, Australia

COMPLETED

Pioneer Clinical Research

Sydney, Australia

RECRUITING

University Ghent

Ghent, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

Rheumazentrum Ruhrgebiet, Ruhr-University Bochum

Bochum, Germany

RECRUITING

Universitätsklinikum Erlangen - Medizinische Klinik 3

Erlangen, Germany

NOT YET RECRUITING

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)

Leiden, Netherlands

NOT YET RECRUITING

ETG Lublin

Lublin, Poland

NOT YET RECRUITING

Reumedika

Poznan, Poland

NOT YET RECRUITING

La Paz University Hospital

Madrid, Fuencarral-El Pardo, 28046, Spain

NOT YET RECRUITING

Reina Sofia University Hospital

Córdoba, Poniente Sur, 14004, Spain

NOT YET RECRUITING

University hospital Parc Tauli de Sabadell

Sabadell, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Axial Spondyloarthritis

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Central Study Contacts

Grey Wolf Therapeutics Patient enquiries

CONTACT

+44 1235644970; enquiries@gwt.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Parts A, B, and C - None (Open Label). Part D will be double-blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 2, 2025
• Study Start: July 28, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); NL (2); ES (3); BE (2); PL (2); AU (3)