Open-label basket study for safety and pharmacokinetics evaluation of INF904 in subjects with CSU or HS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

InflaRx GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

2 Apr 2025 → 16 Jan 2026

Decision date (initial)

2025-03-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

InflaRX

External identifiers

EU CT number

2024-515615-22-00

WHO UTN

U1111-1310-7702

ClinicalTrials.gov

NCT06555328

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Therapy, Pharmacokinetic

To determine the safety of INF904 following multiple oral doses in subjects with moderate to severe CSU or HS

Secondary objectives 1

1. To characterize the Pharmacokinetic (PK) profile of INF904 following multiple oral doses in subjects with moderate to severe CSU or HS

Conditions and MedDRA coding

Moderate to Severe Chronic Spontaneous Urticaria (CSU) or Moderate to Severe Hidradenitis Suppurativa (HS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Capacity of giving signed informed consent.
2. Subjects must be 18 years or older at the time of signing the informed consent.
3. For CSU: Subjects diagnosed with moderate to severe CSU and inadequately controlled by second generation H1-antihistamines at the time of randomization as defined in the following: a. The presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local treatment guidelines during this time period. b. UAS7 score (range 0-42) ≥16 and UCT7 (range 0-16) <12 during 7 days prior to randomization (Day 1). c. Arm 3:CSU subject: As described in the protocol in point i. and ii.
4. CSU diagnosis for ≥ 6 months
5. For CSU: Capable of completing a daily symptom diary for the duration of the study and adhering to the study visit schedules.
6. For CSU: Subjects must not have had any missing diary entries in the 7 days prior to randomization (Day 1).
7. For HS: Moderate or severe HS (with Hurley Stage II or III), and an AN count ≥ 5 at screening and baseline. Inflammatory lesions should affect at least 2 distinct anatomical areas.
8. For HS: Diagnosis of HS based on clinical history and physical examination for at least 6 months prior to the baseline visit; diagnosis must be verifiable through medical notes and documentation.
9. For HS: Stable HS for at least 2 months before screening, as determined by the investigator through subject interview and review of medical history.
10. For HS: Subjects must have had an inadequate response to at least a 3-month (90 days) oral antibiotics treatment for HS (or demonstrated intolerance to or have a contraindication to oral antibiotics for treatment of HS).

Exclusion criteria 28

1. Subjects with known severe or life-threatening hypersensitivity reaction to any other CSU/HS treatment according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE). Subjects with known hypersensitivity to INF904 or to any other ingredient of the study medication.
2. Subjects with known progressed liver disease (Child-Pugh B or C).
3. Subject has any of the following specific abnormalities on screening laboratory tests: a. Hemoglobin: < 10 g/dl b. Platelets: < 100 000/mm3 c. White blood cells: <3 000/mm3 d. Neutrophils:<1 500/mm3 e. Aspartate aminotransferase (AST), or alanine aminotransferase (ALT) ≥3 times ULN f. Alkaline phosphatase (ALP) ≥3 times ULN g. Total bilirubin level (TBL) ≥2 times ULN h. Creatinine: > 1.5 times ULN
4. Women of child-bearing potential (WOCBP), defined as any women physiologically capable of becoming pregnant, unless they are using a highly effective method of contraception while taking study treatment and for 3 months after stopping study medication. Note: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
5. Subjects who plan to become pregnant during the study, are pregnant, or breastfeeding.
6. Male subjects who do not agree to practice an effective method of contraception, during the study and until 3 months after last dose of INF904.
7. Subjects are currently participating in any other active investigational study of an investigational agent.
8. Any existing condition, which according to the judgement of the investigator, will interfere with subjects’ ability to comply with the requirements of the study protocol or will otherwise put the subject at risk (e.g., known alcohol or drug abuse, known cerebral conditions-including psychiatric disorders, planned major surgery during the time of foreseen study participation etc.).
9. For CSU: Subjects who have isolated pruritus or recurrent angioedema in the absence of wheals (hives).
10. For CSU: Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
11. For CSU: Subjects having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria.
12. Subjects who have any other skin disease that may interfere with assessment of CSU or HS.
13. For CSU: Any other skin disease associated with chronic itching that might influence the investigator’s opinion and/or the study evaluations and results, e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis.
14. For CSU: Subjects who received concomitant prohibited medication within: a. 16 weeks prior to baseline (start of treatment with IMP): Anti-IgE therapy. b. 12 weeks prior to baseline (start of treatment with IMP): i. Intravenous immunoglobulins ii. Biological therapy other than anti-IgE therapy iii. Other investigational drugs c. 6 weeks prior to baseline (start of treatment with IMP): Routine (daily or every other day during 5 or more consecutive days) doses of systemic hydroxychloroquine. d. 4 weeks prior to baseline (start of treatment with IMP) i. Routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids or other immunosuppressants ii. Plasmapheresis e. 2 weeks prior to baseline (start of treatment with IMP): Regular (daily or every other day) doxepin (oral) f. 1-week prior baseline (start of treatment with IMP): H2-antihistamines.
15. For CSU: Arms 1 and 2: As described in the protocol.
16. For HS: Treatment with intravenously administered anti-infectives (i.e. antibiotics, antivirals, or antifungals) or oral anti-infectives other than doxycycline, minocycline or other tetracyclines within 4 weeks prior to baseline (start of treatment with IMP). Please note: doxycycline, minocycline or other tetracyclines are only permitted if used for stable chronic treatment of HS symptoms as determined by the investigator during at least the 4 weeks before baseline (start of treatment with IMP), if administered “as needed” then dosing is not considered stable and therefore, not allowed.
17. For HS: Subjects who received any systemic immunosuppressive or immunomodulating drugs (e.g. oral or injectable corticosteroids, methotrexate, cyclosporine and azathioprine) or LAight therapy within 4 weeks prior to baseline (start of treatment with IMP).
18. For HS: Subjects who received other biologic therapy (including, but not limited to adalimumab, infliximab, anakinra, ustekinumab, rituximab, etanercept, golimumab, secukinumab, bimekizumab) within 12 weeks prior to baseline (start of treatment with IMP).
19. For HS: Subjects who received opioid analgesic therapy other than tramadol within 2 weeks prior to baseline (start of treatment with IMP).
20. For HS: Subjects who received deroofing or excisional surgery for HS within 6 weeks prior to baseline (start of treatment with IMP).
21. Subjects who have an active infection or history of infection(s) as follows: a. Any infection requiring systemic treatment within 14 days prior to baseline. b. A history of opportunistic, recurrent, or chronic infections that, in the opinion of the Investigator, might cause this study to be detrimental to the subject.
22. Subjects who received a vaccine within 2 weeks prior to baseline (i.e., start of treatment with IMP).
23. Subjects with known acute or latent tuberculosis, or a known human immunodeficiency virus (HIV) infection or a known history of or suspected current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (hepatitis B surface antigen/hepatitis B virus ribonucleic acid [RNA] positive or hepatitis C virus RNA positive).
24. Subjects with a history of malignancies during the past 3 years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma, or carcinoma of the cervix in situ.
25. Subjects with known congestive heart failure (New York Heart Association criteria Class III or IV).
26. Subjects with documented history of moderate to severe renal impairment
27. History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for subjects participating in the study such as: a. Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree Atrio Ventricular (AV) block without a pacemaker b. History of familial long QT syndrome or known family history of Torsades de Pointes c. Resting heart rate (physical examination or 12-lead ECG) < 50 bpm d. Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or inability to determine the QTcF interval. e. Use of agents known to prolong the QT interval unless they can be safely and permanently discontinued for the duration of study.
28. Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities will be excluded as well as subjects who are employees or direct dependents of the sponsor, investigator, or trial site.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency, severity, and relatedness of treatment- emergent adverse events (TEAEs) and serious adverse events (SAEs) using MedDRA classification.

Secondary endpoints 5

1. Plasma PK parameters of INF904 calculated as appropriate: • Maximum observed plasma concentrations (Cmax)
2. • Minimum observed plasma concentration (Cmin)
3. • Time of occurrence of maximum plasma concentration (tmax)
4. • Systemic exposure, defined as the Area Under Curve AUC0-24, AUClast
5. PK parameters may also be derived from a Population PK (PopPK) model including AUCinf, AUC0--12 hr, AUC0-24 hr, Cmax, tmax, terminal half-life (t½), terminal elimination phase (Vz/F), and apparent oral clearance (CL/F).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

InflaRx GmbH

Sponsor organisation

InflaRx GmbH

Address

Winzerlaer Strasse 2, Ammerbach Ammerbach

City

Jena

Postcode

07745

Country

Germany

Scientific contact point

Organisation

InflaRx GmbH

Contact name

Chief Medical Officer

Public contact point

Organisation

InflaRx GmbH

Contact name

Chief Medical Officer

Third parties 2

Locations

4 EU/EEA countries · 16 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 32 files

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

Application history

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