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

NCT07047703 | Recruiting Phase 1

• 1 other identifier: GRWD0715-AS-01
• Study Type: interventional
• Target: 140
• Locations: 6 countries
• Sites: 16

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 (6)

• Parts A, B and C: Incidence of treatment emergent (TEAE) and treatment related adverse events (TRAEs)

  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).

  Immediately after the first dose of GRWD0715 through to study completion after 4-12 weeks.

• Parts A and B: Incidence and nature of dose limiting events (DLEs).

  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.

  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

• 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

  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.

  This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit

• 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

  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.

  This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit

• 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

  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.

  This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit

• 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

  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

  This will be conducted at Screening, Week 1, Week 4, Week 8, Week 12 and the 15 Day End of Study visit

Secondary Outcomes (7)

• Parts A, B and C: PK - trough concentrations (Cmin)

  Part A: From first dose to Day 4 Part B: From first dose to Day 28 Part C: Immediate Rollover: Week 4, 8 and 10 Returning Rollover: Week 1, 4 and 8

• Parts A, B and C: PK - maximum observed concentration (Cmax)

  Part A: From first dose to Day 4 Part B: From first dose to Day 28 Part C: Immediate Rollover: Week 4, 8 and 10 Returning Rollover: Week 1, 4 and 8

• Parts A, B and C: PK - time to Cmax (Tmax)

  Part A: From first dose to Day 4 Part B: From first dose to Day 28 Part C: Immediate Rollover: Week 4, 8 and 10 Returning Rollover: Week 1, 4 and 8

• Parts A, B and C: PK - area under the concentration-time curve (AUC0-t)

  Part A: From first dose to Day 4 Part B: From first dose to Day 28 Part C: Immediate Rollover: Week 4, 8 and 10 Returning Rollover: Week 1, 4 and 8

• Parts A, B and C: PK - half-life (t1/2)

  Part A: From first dose to Day 4 Part B: From first dose to Day 28 Part C: Immediate Rollover: Week 4, 8 and 10 Returning Rollover: Week 1, 4 and 8

Study Arms (4)

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

EXPERIMENTAL

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

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) of GRWD0715 Participants in Part B will receive GRWD0715 for 28 days

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

Part C - Safety expansion cohort participants with axSpA

EXPERIMENTAL

Participants who previously completed Part B and OR randomized to the placebo arm in Part D: Part C - Open-label safety expansion cohort with GRWD0715 Participants from Part B or Part D of the study will be permitted to participate in Part C will receive GRWD0715 for 8 or 12 weeks, respectively.Immediate rollovers from Part B: If Part C is open while a Part B cohort is enrolling, participants may roll over directly into Part C without a washout period and continue treatment at their current assigned dose level of GRWD0715 from Part B, once daily, for an additional 8 weeks. Returning rollovers from Part B: If Part C is open, participants from previously completed Part B cohorts may return to enrol in Part C at the Part B dose currently reviewed and approved by the Safety Review Committee at the time of their return, once daily, for up to an additional 8 weeks. Placebo Rollovers from Part D: will receive 12 weeks of open-label, daily dosing with GRWD0715 in Part C

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

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

EXPERIMENTAL

Part D - Randomised expansion cohort of GRWD0715 vs. placebo Depending on the data from Part B, and the availability of one or more biologically active doses that are safe and well tolerated, participants will be randomised to receive either one or two dose levels of GRWD0715, or placebo to match (PTM). If one dose level is selected, participants will be randomised in a 4:1 ratio (GRWD0715:PTM). If two dose levels are selected, participants will be randomised in a 2:2:1 ratio (two GRWD0715 dose arms and PTM). Treatment will be administered once daily for up to 12 weeks.

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 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

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 C - Safety expansion cohort in participants with axSpA DRUG

Participants in Part C will receive GRWD0715 for 12 weeks

Part C - Safety expansion cohort 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, 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:

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
• Parts B and D only: Participants previously treated with three or more b/tsDMARDs
• Participants currently receiving prohibited conventional DMARDS cDMARDS), thalidomide (including previous use) or other prohibited concomitant medications.
• Inadequate Haematologic function, defined as:
• Haemoglobin \<10 g/dL.
• Absolute white blood cell count \<3.0 x 10\^9 /L (\<3000 mm\^3)
• Absolute neutrophil count \<1.2 x 10\^9 /L (\<1200 mm\^3)
• Absolute lymphocyte count \<1.0 x 10\^9 /L (\<1000 mm\^3)
• 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

Sponsors & Collaborators

• Grey Wolf Therapeutics: lead

Study Sites (16)

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, 30-002, Poland

NOT YET RECRUITING

ETG Lublin

Lublin, Poland

RECRUITING

Reumedika

Poznan, Poland

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: September 18, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); NL (2); ES (3); BE (2); PL (3); AU (4)