T-Guard in dcSSc

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philikos B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Apr 2025 → ongoing

Decision date (initial)

2025-02-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Radboudumc · Top Consortium Knowledge and Innovation - Top Sector Life Sciences & Health (TKI-LSH) Foundation · Philikos BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety

To evaluate the safety of T-Guard in patients with early diffuse cutaneous systemic sclerosis (dcSSc), evaluated in all 13 study participants

Secondary objectives 2

1. To evaluate overall long-term safety and assess efficacy during the first 12 months after initiation of therapy, with efficacy analyses conducted separately for: a. The 12 participants enrolled under protocol version 3.0 or later (intended-use population), in whom continuation of background MTX or MMF is required, and b. Participant 1, enrolled under protocol version 2.0 with mandatory stopping of background therapy.
2. To characterize the pharmacokinetics and immunogenicity of T-Guard in all treated participants (N=13)

Conditions and MedDRA coding

diffuse cutaneous systemic sclerosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Aged between 18-75 at the time of signing informed consent.
2. With early dcSSc, defined as skin involvement above and below elbows and/or knees, disease duration ≤36 months from first non-Raynaud phenomenon.
3. Modified Rodnan skin scores (MRSS) scores ≥15
4. Progressive skin or musculoskeletal (MKS)disease, e.g. worsening of skin with new areas of involvement or tendon friction rubs (TFR), with either Health Assessment Questionnaire Disability Index (HAQ-DI) >1.0 or elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP).
5. Interstitial lung disease (ILD) with forced vital capacity (FVC) 50-<80% predicted or lung diffusion testing (DLCO)(Hb corrected) 45-75% or >10% lung involvement on visual rad high-resolution computed tomography (HRCT) scan or those with progressive ILD, defined as progressive pulmonary fibrosis (PPF)-ILD in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851481/.
6. Participants should have failed at least one established systemic immunosuppressive treatment for dcSSc (e.g., MTX, MMF , azathioprine, rituximab, tocilizumab, intravenous immunoglobulin [IVIG], or cyclophosphamide), each tried for at least 3 months, and: a. Have received treatment with MTX or MMF for at least 3 months prior to enrollment, with the dose stable for at least 8 weeks prior to enrollment; and b. Be able and willing, in the opinion of the investigator, to continue this background therapy at the stable dose throughout the study, unless dose reduction or discontinuation is clinically indicated due to adverse events.
7. Participants should have given written informed consent

Exclusion criteria 20

1. Creatinine greater than or equal to 2mg/dL or creatinine clearance less than 60 mL/min or requiring hemodialysis. History or presence of glomerulonephritis, acute tubular necrosis, and/or interstitial nephritis or clinically significant findings as determined by urinalysis at screening
2. Platelets <100,000/mm3
3. Evidence of heart failure defined as left ventricular ejection fraction (LVEF) <45% as assessed by either echocardiography or multigated acquisition (MUGA) scan in the last 6 months
4. Echocardiographic features consistent with pulmonary hypertension, unless right heart catheterization (RHC) is normal
5. Moderate to severe restrictive lung disease defined as FVC <50% predicted and/or DLCO Hb-corrected <45% predicted and presence of ILD on HRCT
6. Patients who have been diagnosed with scleroderma renal crisis (SRC) or another cause TMA anytime during their lifetime.
7. Albumin of less than or equal to 25 g/L
8. Creatine kinase (CK) level greater than 5 times the upper limit of normal (ULN)
9. Hemoglobulin (Hb) <9 g/dl
10. White blood cell count (WBC) <3000 µl
11. On continuous oxygen therapy
12. Significant gastrointestinal (GI) dysmotility requiring total parenteral nutrition or G or J tube
13. Latent infection with mycobacterium tuberculosis, unless history of treatment.
14. Known active infection with Hepatitis B, C, or E at screening (prior infections are not excluded), HIV or HTLV1 positivity.
15. Malignancy within the past 5 years, except for non-melanoma skin cancer or cervical cancer situ.
16. Vascular prosthesis.
17. Need for mechanical ventilation and/or vasopressor support or requiring hemodialysis.
18. Uncontrolled infection (infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present) are not eligible for this trial.
19. Known hypersensitivity to any of the components of murine monoclonal antibodies (mAb), or Recombinant Ricin Toxin A-chain (RTA).
20. Participants who continue to receive any systemic treatment for systemic sclerosis, other than MTX or MMF, including but not limited to azathioprine, cyclosphosphamide, IVIG, rituximab, and tocilizumab, within three months prior to the baseline visit will be excluded. Continuation of oral corticosteroids (≤10 mg/day of prednisone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) is permitted if the participant is on a stable dose for at least two weeks prior to and including the baseline visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of Grade 3 or higher adverse events (AEs), based on CTCAE v5, occurring in the period from the first T-Guard infusion until 28 days after the last T-Guard administration.

Secondary endpoints 16

1. Incidence of AEs occurring during 180 days after treatment start
2. Incidence of infectious AEs occurring during 180 days after treatment start
3. Incidence of SAEs occurring during 180 days after treatment start, and - if considered related to T-Guard treatment - occurring in the period of 180 until 365 days after treatment start
4. Incidence of AESIs occurring during 180 days after treatment start, and - if considered related to T-Guard treatment - occurring in the period of 180 until 365 days after treatment start: hypoalbuminemia; thrombocytopenia; microangiopathy.
5. All-cause mortality during 365 days after treatment start
6. Immunogenicity of T-Guard
7. Pharmacokinetics of T-Guard
8. Achieving revised CRISS-25 scores at study day 90, 180, 270 and 365 compared to baseline.
9. Achieving revised CRISS-50 scores at study day 90, 180, 270 and 365 compared to baseline.
10. Achieving revised CRISS-75 scores at study day 90, 180, 270 and 365 compared to baseline.
11. Achieving revised CRISS-100 scores at study day 90, 180, 270 and 365 compared to baseline.
12. mRSS at study day 36, 90, 180, 270 and 365 compared to baseline.
13. Pulmonary function test results (FVC and DLCO % predicted) at study day 180 and 365 compared to baseline.
14. HRCT quantification at at study day 180 and 365 compared to baseline.
15. Other patient reported measures of function and Quality of Life questionnaires: SHAQ, SF-36, UCLA SCTC GIT 2.0 and EQ5d at study day 36, 90, 180, 270 and 365 compared to baseline.
16. Organ worsening as defined in Step 1 of the revised CRISS- 25 score during 365 days after treatment start.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philikos B.V.

Sponsor organisation

Philikos B.V.

Address

Javastraat 122

City

Nijmegen

Postcode

6524 ML

Country

Netherlands

Scientific contact point

Organisation

Philikos B.V.

Contact name

Ypke van Oosterhout

Public contact point

Organisation

Philikos B.V.

Contact name

Ypke van Oosterhout

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications