Axial Spondyloarthritis (AxSpA)Phase 1/2EAST-1NCT07047703
EAST-1 (ERAP-inhibition in Axial Spondyloarthritis Trial - 1)
A Phase 1/2 study testing Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers, Part B - Multiple Ascending Dose (MAD) in participants with axSpA and Part C - Safety expansion cohort in participants with axSpA in people with Axial Spondyloarthritis (AxSpA), run by Grey Wolf Therapeutics at 16 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Axial Spondyloarthritis (AxSpA)
- What is being tested?
- Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers, Part B - Multiple Ascending Dose (MAD) in participants with axSpA and Part C - Safety expansion cohort in participants with axSpA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 16 sitesin 6 countries
- Study dates
- 28 Jul 2025to 30 Sep 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
- Presence of active anterior uveitis
Trial locations and contacts
16 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
16 sites in 6 countries
Australia4 sites, 3 recruiting
- Recruiting
University of the Sunshine Coast (UniSC)
Birtinya
- Completed
University of the Sunshine Coast (UniSC)
Morayfield
- Recruiting
The Colin Bayliss Research and Teaching Unit
Perth
- Recruiting
Pioneer Clinical Research
Sydney
Poland3 sites, 3 recruiting
- Not yet recruiting
Malopolskie Badania Kliniczne (MBK Clinic)
Krakow, Małopolska, 30-002
- Recruiting
ETG Lublin
Lublin
- Recruiting
Reumedika
Poznan
Spain3 sites, 3 recruiting
- Not yet recruiting
Reina Sofia University Hospital
Córdoba, Poniente Sur, 14004
- Not yet recruiting
La Paz University Hospital
Madrid, Fuencarral-El Pardo, 28046
- Not yet recruiting
University hospital Parc Tauli de Sabadell
Sabadell
Belgium2 sites, 2 recruiting
- Recruiting
University Ghent
Ghent
- Recruiting
UZ Leuven
Leuven
Germany2 sites, 2 recruiting
- Recruiting
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum
Bochum
- Not yet recruiting
Universitätsklinikum Erlangen - Medizinische Klinik 3
Erlangen
Netherlands2 sites, 2 recruiting
- Recruiting
Amsterdam University Medical Center
Amsterdam
- Not yet recruiting
Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)
Leiden
About this study
Official title: A Multi-part, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD0715 in Healthy Human Volunteers and Participants With Axial Spondyloarthritis
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.
Read the detailed description
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.
ERAP1 is involved in trimming antigens from foreign bodies (e.g. bacteria, viruses) which are presented on the surface of a cell to trigger an immune response. In axSpA, it is thought an antigen from the person's own body, called a 'self-peptide' is presented by the ERAP1 processing pathway and incorrectly recognised by the immune system. The hypothesis is that stimulation of the immune system by the presentation of this self-peptide causes the inflammatory symptoms experienced by people living with axSpA.
As an inhibitor of ERAP1, GRWD0715 aims to prevent the generation of the antigenic self-peptide, and thus remove the stimulus of the immune system. If the immune system is not activated, the immune attack on the sacroiliac joint (SIJ) and spine would stop, halting the axSpA disease progress.
The study will consist of 4 parts: Part A conducted in healthy human volunteers, and Part B, Part C and/or D in participants with axSpA. The primary goal of Parts A, B and C is to assess whether GRWD0715 is safe and well tolerated in healthy human volunteers and participants with axSpA. The primary goal of Part D is to review whether GRWD0715 is efficacious when compared to placebo.
- Conditions
- Axial Spondyloarthritis (AxSpA)
- Being tested
- Part A - Single Ascending Dose (SAD) in Healthy Human Volunteers, Part B - Multiple Ascending Dose (MAD) in participants with axSpA, Part C - Safety expansion cohort in participants with axSpA, Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA
- Keywords
- Axial Spondyloarthritis, AxSpA
- Medical subject headings
- Axial Spondyloarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A - Single Ascending Dose (SAD) in Healthy Human VolunteersDrug
Participants in Part A will receive a single dose of GRWD0715 on Day 1 only.
Part B - Multiple Ascending Dose (MAD) in participants with axSpADrug
Participants in Part B will receive GRWD0715 for 28 days
Part C - Safety expansion cohort in participants with axSpADrug
Participants in Part C will receive GRWD0715 for 12 weeks
Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpADrug
Participants in Part D will receive GRWD0715 or placebo-to-match for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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 Receives: 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. Receives: Drug: Part D - Randomised, placebo-controlled, expansion cohort in participants with axSpA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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)
PK samples will be collected during the study to measure the to measure how the study drug moves into, through, and out of the body over time, and how its concentration in the body changes over time. Whole blood will be collected for the determination of GRWD0715 levels in plasma. The trough is the lowest concentration of a drug reached in the body, it is collected from a blood sample drawn immediately before administering the next scheduled dose.
Measured: 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)
The Cmax is the highest measured drug concentration in the blood or plasma after a dose and is measured or identified directly as the highest peak data point on the experimental concentration-time graph.
Measured: 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)
This is the exact time elapsed from drug administration until the peak concentration (Cmax) is reached and is found by looking at the time value on the x-axis that corresponds directly to the peak concentration of the drug in the blood.
Measured: 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)
A measure of the total drug exposure in the body from time zero up to the timepoints specified below for each study Part.
Measured: 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)
The time required for the GRWD0715's plasma concentration to decrease by exactly 50% during the final elimination phase.
Measured: 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
Part B: A Biologically Active Dose (BAD) will be identified
A BAD is defined as a dose level with evidence supporting a biological effect of
GRWD0715. A BAD will be identified based on meeting at least one of the following pre-specified criteria:
Steady state pharmacokinetics: Dose levels achieving mean steady-state Cavg concentration at or above a predefined threshold of 1166 ng/ml will be considered to provide sufficient target engagement to meet the definition of a BAD. This threshold corresponds to the predicted IC50 as a relative Cavg concentration and is supported by human PK-PD modelling of a related oral ERAP1 inhibitor (GRWD5769) in oncology, which demonstrated that significant immunopeptidome shifts occur at levels that achieve PK exposures ≥ predicted IC50 as a relative Cavg concentration.
Preliminary signals of clinical activity, including clinically important improvements in validated disease activity measures (e.g., ASDAS).
Other supporting evidence may be considered including evidence of pharmacodynamic activity.
Measured: The Biologically Active Dose will be assessed every 3 months in Part B on the completion of each of the 6 dose cohorts for up to a total of 14 months.
Parts A, B and C: Maximum tolerated dose (MTD): the MTD will be determined by the incidence of DLEs according to the MTD evaluation process.
Multiple ascending doses will be evaluated in this study. The MTD will be decided using a BOIN design escalation/de-escalation/elimination criteria model. If the true DLE rate is greater than 0.22 for a dose level, no future participants can be dosed at that level or higher.
Measured: MTD will be assessed on the completion of each dose level cohort.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start28 Jul 2025
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Axial Spondyloarthritis (AxSpA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Grey Wolf Therapeutics
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07047703
- Sponsor's protocol ID
- GRWD0715-AS-01
- Acronym
- EAST-1
- Status last verified
- Sep 2026
- First submitted
- 24 Jun 2025
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD may not be shared for this Phase 1 study, or the IPD plan may be updated at a later point