Phase 2a Open-Label Basket Study Evaluating Safety and Pharmacokinetics of INF904 in Moderate to Severe Chronic Spontaneous Urticaria and Hidradenitis Suppurativa

Trial ID: 2024-515615-22-00
Protocol: INF904-P2.1
Sponsor: InflaRx GmbH

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Diseases & Conditions

Hidradenitis Chronic spontaneous urticaria

Objectives

The primary objective of this study is to determine the **safety** of INF904 following multiple oral doses in subjects with moderate to severe **Chronic Spontaneous Urticaria (CSU)** or **Hidradenitis Suppurativa (HS)**. Evaluating the safety profile of INF904 is clinically relevant as it ensures the therapeutic agent does not pose undue risk to patients, which is crucial for its potential use in managing these conditions.

Secondary objectives include characterizing the **pharmacokinetic (PK) profile** of INF904 after multiple oral doses in the same patient population. Understanding the PK profile is important for determining the appropriate dosing regimen and ensuring optimal therapeutic efficacy while minimizing adverse effects.

Participants

The clinical trial involves a total of **15 participants** diagnosed with either **Moderate to Severe Chronic Spontaneous Urticaria (CSU)** or **Moderate to Severe Hidradenitis Suppurativa (HS)**. The study population includes both male and female subjects, aged 18 years and older, who are capable of providing informed consent. Participants were selected based on their inadequate response to standard treatments for their respective conditions, such as oral antibiotics for HS or second-generation H1-antihistamines for CSU. The trial includes individuals with stable health conditions, as determined by clinical history and physical examination, and excludes those with missing diary entries or unstable disease states. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial population also includes vulnerable groups, ensuring a comprehensive assessment of the safety of the investigational product, INF904, across diverse demographics.

Plans and Procedures

The clinical trial is a **Phase 2a** open-label basket study designed to evaluate the safety and pharmacokinetics of **INF904**, an oral C5aR1 inhibitor, in subjects with moderate to severe **chronic spontaneous urticaria** (CSU) or **hidradenitis suppurativa** (HS). The trial will involve multiple oral doses of INF904, administered in the form of soft capsules. The study is not categorized as a low-intervention trial and is expected to run from March 1, 2025, to December 24, 2025. Participants will be involved for a maximum treatment period of 28 days.

The trial design includes several key elements of research methodology. It is an open-label study, meaning both the researchers and participants will be aware of the treatment being administered. The primary endpoint is to assess the frequency, severity, and relatedness of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) using the MedDRA classification. Secondary endpoints include the evaluation of plasma pharmacokinetic (PK) parameters of INF904, such as maximum observed plasma concentrations (Cmax), minimum observed plasma concentration (Cmin), and systemic exposure defined as the area under the curve (AUC).

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed. Participants must be 18 years or older and capable of providing informed consent. For HS, subjects must have had an inadequate response to at least a 3-month oral antibiotics treatment or demonstrated intolerance or contraindication to such treatment. For CSU, subjects must have a diagnosis of moderate to severe CSU inadequately controlled by second-generation H1-antihistamines, with specific criteria for itch, hives, and UAS7 and UCT7 scores. Follow-up visits will monitor safety and PK parameters, with the end-of-study visit concluding the participant's involvement.

Participants are expected to adhere to the study visit schedules and complete a daily symptom diary for the duration of the study. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation of the treatment. The trial aims to provide valuable data on the safety profile and pharmacokinetics of INF904 in the target population.

Treatment

The clinical trial involves the administration of **INF904**, an experimental medication developed by INFLARX GMBH. **INF904** is formulated as a **CAPSULE, SOFT** and is intended for oral administration. The active substance, also named **INF904**, is of chemical origin. The trial aims to evaluate the safety and pharmacokinetics of this oral **C5aR1 inhibitor** in subjects with moderate to severe **chronic spontaneous urticaria** or **hidradenitis suppurativa**. The maximum treatment period for **INF904** is 28 days. The dosage and frequency of administration are determined by the study protocol, although specific dosing details are not provided in the available data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment regimen.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial data. The study is designed as an open-label basket study, which implies that all participants will receive the experimental treatment without blinding or randomization. The primary objective is to assess the safety profile of **INF904** following multiple oral doses in the specified patient population. The trial does not include a pediatric formulation, and the product is not classified as an orphan drug. The trial's design and execution will adhere to regulatory standards to ensure the integrity and reliability of the collected data.

Efficacy

Efficacy in this clinical trial will be assessed through the evaluation of primary and secondary endpoints. The primary endpoint focuses on the safety profile of the investigational product, INF904, by monitoring the frequency, severity, and relatedness of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) using the MedDRA classification system. This will provide insights into the safety and tolerability of the drug in subjects with moderate to severe **Chronic Spontaneous Urticaria (CSU)** or **Hidradenitis Suppurativa (HS)**.

Secondary endpoints will involve the assessment of pharmacokinetic (PK) parameters of INF904. These parameters include maximum observed plasma concentrations (Cmax), minimum observed plasma concentration (Cmin), time of occurrence of maximum plasma concentration (tmax), and systemic exposure, defined as the Area Under Curve (AUC0-24, AUClast). Additional PK parameters may be derived from a Population PK (PopPK) model, which includes AUCinf, AUC0-12 hr, AUC0-24 hr, Cmax, tmax, terminal half-life (t½), terminal elimination phase (Vz/F), and apparent oral clearance (CL/F). These measurements will be collected and analyzed to understand the drug's absorption, distribution, metabolism, and excretion characteristics.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Capacity of giving signed informed consent.
Subjects must be 18 years or older at the time of signing the informed consent.
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.
CSU diagnosis for ≥ 6 months
For CSU: Capable of completing a daily symptom diary for the duration of the study and adhering to the study visit schedules.
For CSU: Subjects must not have had any missing diary entries in the 7 days prior to randomization (Day 1).
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.
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.
For HS: Stable HS for at least 2 months before screening, as determined by the investigator through subject interview and review of medical history.
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).

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Exclusion Criteria

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.
Subjects with known progressed liver disease (Child-Pugh B or C).
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
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.
Subjects who plan to become pregnant during the study, are pregnant, or breastfeeding.
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.
Subjects are currently participating in any other active investigational study of an investigational agent.
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.).
For CSU: Subjects who have isolated pruritus or recurrent angioedema in the absence of wheals (hives).
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).
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.
Subjects who have any other skin disease that may interfere with assessment of CSU or HS.
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.
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.
For CSU: Arms 1 and 2: As described in the protocol.
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.
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).
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).
For HS: Subjects who received opioid analgesic therapy other than tramadol within 2 weeks prior to baseline (start of treatment with IMP).
For HS: Subjects who received deroofing or excisional surgery for HS within 6 weeks prior to baseline (start of treatment with IMP).
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.
Subjects who received a vaccine within 2 weeks prior to baseline (i.e., start of treatment with IMP).
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).
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.
Subjects with known congestive heart failure (New York Heart Association criteria Class III or IV).
Subjects with documented history of moderate to severe renal impairment
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.
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.