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

NCT07047703 · tracked via the Priya Life Science Australia tracker

Sponsor

Grey Wolf Therapeutics

Phase

Phase 1/2

Started

2025-07-28

Last updated

2026-09-18

Condition(s) studied

Axial Spondyloarthritis (AxSpA)

Investigational drug(s) / intervention(s)

Part A - Single Ascending Dose (SAD) in Healthy Human VolunteersPart B - Multiple Ascending Dose (MAD) in participants with axSpAPart C - Safety expansion cohort in participants with axSpAPart D - Randomised, placebo-controlled, expansion cohort in participants with axSpA

Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers: Participants in Part A will receive a single dose of GRWD0715 on Day 1 only.

Part B - Multiple Ascending Dose (MAD) in participants with axSpA: Participants in Part B will receive GRWD0715 for 28 days

Part C - Safety expansion cohort in participants with axSpA: Participants in Part C will receive GRWD0715 for 12 weeks

Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA: Participants in Part D will receive GRWD0715 or placebo-to-match for 12 weeks

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

65 Years

Healthy volunteers

Key Inclusion Criteria: 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 * Participant must be able and willing to comply with the requirements of the protocol (including dietary restrictions and exclusion of grapefruit juice) * 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, defined as 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. o Objective evidence of inflammation may not be required for Part B. Participants who do not require objective evidence of inflammation require Sponsor approval prior to screening for and/or enrolling to the study. * A score of: * ≥ 2.1 (High Disease Activity) on the Ankylosing Spondylitis Disease Activity Score (ASDAS) on current treatment\* OR * In Part B only, A: a score of \>1.3 (Low to Moderate Disease Activity) on the ASDAS on current treatment. Participants with a score of ≥1.3 and \< 2.1 require Sponsor approval prior to screening for the study. * At least one of the following: * Current treatment with a NSAID, at a n adequate dose and duration per local clinical guidelines, with inadequate clinical response OR * Intolerance to ≥1 NSAID or contraindication(s) to NSAIDs Participants may have received 1 or 2 (Australia only) prior b/tsDMARD and discontinued due to intolerance or inadequate efficacy provided that: Part B: Participants who have received two prior b/ts DMARDs require Sponsor approval prior to screening. Part D: Participants with prior b/tsDMARD treatment may be capped. • Participants who have received 1/(Australia only) 2 prior treatments are required to undergo a washout at minimum: Biologic DMARDs 4 weeks or 5 half-lives prior to Day 1, whichever is longer. Any JAK inhibitor DMARDs 2 weeks prior to Day 1 Part C only: Participants enrolling into Part C must: * Have completed Part B or Part D treatment per protocol. * Have not permanently discontinued GRWD0715 due to safety concerns. * Have no ongoing safety issues that, in the opinion of the Investigator, would preclude further treatment. * Provide written informed consent to participate in Part C. Part D only: Participants must be GRWD0715 naïve. Contacts/Locations Central Contact Person: Grey Wolf Therapeutics Patient enquiries Telephone: +44 1235644970 Key Exclusion Criteria: Healthy Volunteers * History or presence of any clinically significant findings in medical history, physical examination, vital signs and/or laboratory tests that, in the opinion of the Investigator, would preclude inclusion in the study * 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 * Parts B and D only: Participants previously treated with three or more b/tsDMARDs * Participants not meeting inclusion criteria for prior b/tsDMARD exposure or required washout period for their respective study part. * Participants currently receiving prohibited conventional DMARDS cDMARDS), thalidomide (including previous use) or other prohibited concomitant medications. * Inadequate Haematologic function, defined as: 1. Haemoglobin \<10 g/dL. 2. Absolute white blood cell count \<3.0 x 10\^9 /L (\<3000 mm\^3) 3. Absolute neutrophil count \<1.2 x 10\^9 /L (\<1200 mm\^3) 4. Absolute lymphocyte count \<1.0 x 10\^9 /L (\<1000 mm\^3) 5. Platelet count \<100 x 10\^9 /L (\<100.000 mm\^3) * 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 * Presence of active anterior uveitis

Primary outcome measure(s)

Parts A, B and C: Incidence of treatment emergent (TEAE) and treatment related adverse events (TRAEs) — Immediately after the first dose of GRWD0715 through to study completion after 4-12 weeks.
Any adverse event AE reported or observed after the start of dosing with any study treatment until completion of the last study related procedure (includes follow-up for safety assessments) will be recorded as a treatment-emergent AE (TEAE). If the TEAE is considered related to the study drug as per the definitions of relatedness listed in ('possibly', 'probably' or 'definitely' related) it will be considered a treatment-related AE (TRAE).
Parts A and B: Incidence and nature of dose limiting events (DLEs). — Part A: the DLE period will be 15 Days from the start of dosing Part B: the DLE period will be 35 days from the start of dosing
DLEs are on Grade 2 (moderate) events that are classified as related to study drug and are not resolved within 7 days. Any Grade 2 events lasting longer than 7 days, events of a higher grade, events that require study drug discontinuation or which meet the criteria for Seriousness and are related to study drug are counted as DLEs.
Analysis of clinical response per Assessment of SpondyloArthritis International Society (ASAS) core outcome set compared to placebo. Higher scores mean worse outcome: Continuous Calculated Scores — This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit
The ASAS core outcome set (COS) will be conducted in participants and includes the following questionnaires which use Continuous Calculated Scores: Ankylosing Spondylitis Disease Activity Score (ASDAS)- A specific mathematically weighted index that combines patient-reported outcomes and blood inflammatory markers. Bath Ankylosing Spondylitis Function Index (BASFI) - A mean score derived from 10 individual visual/numeric questions regarding physical function. Assessment of SpondyloArthritis (ASAS) Health Index - A composite health and functioning score calculated from a specific 17-item questionnaire.
Analysis of clinical response per Assessment of SpondyloArthritis International Society (ASAS) core outcome set compared to placebo. Higher scores mean worse outcome: Numeric Rating Scales — This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit
The ASAS core outcome set (COS) will be conducted in participants and includes the following questionnaires which use numeric rating scales (0-10): NRS Patient Global Assessment of Disease Activity (PGA-DA): A single 0-10 scale rating overall disease impact. NRS total back pain (BASDAI Q2): A single 0-10 scale rating spinal pain. NRS fatigue (BASDAI Q1): A single 0-10 scale rating tiredness levels. NRS average duration and severity of morning stiffness (BASDAI \[Q5+Q6\]/2): An average calculation derived from two separate 0-10 numeric rating scales.
Analysis of clinical response per Assessment of SpondyloArthritis International Society (ASAS) core outcome set compared to placebo. Higher scores mean worse outcome: Direct Anatomical Counts — This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit
The ASAS core outcome set (COS) will be conducted in participants and includes the following assessments which use direct anatomical counts: 44 swollen joint count (Part D): A literal tally of how many joints out of 44 are actively swollen. Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (Part D only): A tally of painful areas out of 13 specific enthesitic insertion sites. Dactylitis count: A literal tally of the number of digits (fingers and toes) exhibiting uniform swelling (Part D only) ASAS20 and ASAS 40 scores will be calculated from constituent questions within the ASAS COS clinical outcome measures and patient reported outcome measures.
Analysis of clinical response per SPARCC MRI (magnetic resonance imaging) Activity of the sacroiliac joints and spine in the core outcome set compared to placebo — This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit
The SPARCC Scoring System measures active inflammation and structural joint damage in the sacroiliac joints using MRI, through the following: Inflammation Scoring (Bone Marrow Edema): Slice selection: Evaluates six consecutive, specialized coronal MRI slices through the joint. Joint quadrants: Divides each sacroiliac joint into four distinct quadrants (upper and lower iliac, upper and lower sacral). Basic scoring: Gives 1 point for the presence of bone marrow edema in each quadrant. Intensity and depth bonuses: Adds extra points for lesions that show very high signal intensity or great depth (\>1 cm). Maximum score: Reaches a total high score of 72 points for inflammation Structural Damage Scoring: Erosions: Measures loss of bone at the joint surface. Fat lesions: Tracks areas where bone marrow is replaced by fat. Backfill and ankylosis: Detects tissue repair and joint fusion

Trial sites (16)

Facility	City	Region	Status
University of the Sunshine Coast (UniSC)	Birtinya	Australia	Recruiting
University of the Sunshine Coast (UniSC)	Morayfield	Australia	Completed
The Colin Bayliss Research and Teaching Unit	Perth	Australia	Recruiting
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
Malopolskie Badania Kliniczne (MBK Clinic)	Krakow	Małopolska	Not Yet Recruiting
ETG Lublin	Lublin	Poland	Recruiting
Reumedika	Poznan	Poland	Recruiting
La Paz University Hospital	Madrid	Fuencarral-El Pardo	Not Yet Recruiting
Reina Sofia University Hospital	Córdoba	Poniente Sur	Not Yet Recruiting
University hospital Parc Tauli de Sabadell	Sabadell	Spain	Not Yet Recruiting

More Grey Wolf Therapeutics trials in Australia

EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1) Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07047703 on ClinicalTrials.gov ↗ ← All trials in Australia