Clinical trial NCT06191042: A Study to Evaluate the Safety and Tolerability, and the Efficacy of Si-544 in Adults With Psoriasis Vulgaris or Psoriatic Arthritis
Official title: A Multicenter, Phase 1b, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability, and the Efficacy of Si-544 in Adults With Psoriasis Vulgaris or Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Psoriasis Vulgaris
Psoriatic Arthritis
Lead sponsor: selectION Therapeutics GmbH
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2024-01-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to investigate the safety and tolerability of si-544.

Other objectives are to study the metabolism of si-544 in the body and to assess the effects of si-544 on cells of the body's immune system (immune cells) that have been chronically activated by the disease. Likewise, the effect of si-544 on inflammatory responses in the body triggered by the disease and other disease symptoms will be investigated.


Eligibility criteria: Inclusion Criteria:

1. Subject has the capacity for consenting, was informed about the nature, the scope, and the relevance of the clinical study, voluntarily agrees in participation and in the study provisions, and duly signed the ICF approved by the ethics committee before any study-related procedure is performed
2. Men and women aged ≥18 to 75 years
3. Willing and able to adhere to the protocol requirements
4. Women of childbearing potential must:

   1. have a negative pregnancy test (blood) at Screening and a negative pregnancy test (urine) at Day 1
   2. agree to use, and be able to comply with, highly effective measures of contraceptive control (failure rate less than 1% per year when used consistently and correctly) without interruption, from Screening through 30 days after the last IMP injection

   Reliable methods for this study are:

   i. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) iii. intrauterine device iv. intrauterine hormone-releasing system v. bilateral tubal occlusion vi. vasectomized sexual partner (provided that the partner is the sole sexual partner of the woman of childbearing potential and has received medical assessment of the surgical success) vii. sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment) Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods and withdrawal\] is not an acceptable method of contraception).

   c. agree to abstain from breast feeding during the study participation and for 90 days after the last IMP injection
5. Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile women (tubal ligation, hysterectomy, or bilateral oophorectomy)
6. Men must agree to practice true abstinence or to use a condom during sexual contact with a pregnant woman or a woman of childbearing potential during study participation and for at least 90 days after the last IMP injection, even after undergoing a successful vasectomy.

   Ps-specific inclusion criteria:
7. Diagnosis of Ps at least 3 months before Screening
8. Active Ps with ≥3% BSA involved and with at least 1 psoriatic plaque (other than nail change)

PsA-specific inclusion criteria:

7. Diagnosis of PsA based on the classification for psoriatic arthritis criteria (CASPAR) at least 3 months before Screening

8. Diagnosis of active Ps with at least 1 psoriatic plaque (other than nail change)

9. Active PsA defined as

1. ≥1 tender joint out of 68 assessed joints, and
2. ≥1 swollen joint out of 66 assessed joints (dactylitis of a digit counts as one joint each), and
3. negative results for rheumatoid factor and anti-cyclic citrullinated peptide antibodies

Exclusion Criteria:

1. Known history of hypersensitivity to constituents or excipients in the pharmaceutical formulation of the IMP
2. Uncontrolled hypertension or uncontrolled diabetes, as judged by the investigator
3. Chronic disease other than Ps or PsA not adequately controlled by stable treatment (ie, no changes or initiation of treatment within 4 weeks before Screening and Day 1)
4. History of seizures
5. Presence or history of paresthesia or neuropathy
6. Clinically significant ECG abnormalities, as judged by the investigator
7. Clinically relevant disease which could affect the safety of the subject during the study or impede the subject's ability to complete the study, as assessed by the investigator
8. Presence of acute infection within 7 days before Screening or Day 1, as judged by the investigator
9. Known or active infection with Mycobacterium tuberculosis and/or positive tuberculosis interferon γ release assay result at Screening
10. Known or active infection with HIV, hepatitis B virus, or hepatitis C virus
11. Known or suspected abuse of alcohol, drugs, or medicinal products
12. Therapy with biologics used for the treatment of Ps and/o PsA (including those under investigation) within 1 year before Day 1
13. UV phototherapy or systemic therapy (except methotrexate for the treatment of PsA) within 4 weeks of Day 1
14. Vaccination within 2 weeks (for live vaccines within 4 weeks) before Day 1 and/or planned vaccination during the treatment period
15. Current or previous (within 4 weeks before Day 1) participation in another clinical study with an IMP or a medical device
16. Employee of the sponsor, or employee, or relative of the investigator
17. Committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
18. Legal incapacity or limited legal capacity

    Ps-specific exclusion criteria:
19. Drug-induced psoriasis

PsA-specific exclusion criteria:

19. Late stage PsA with deformed joints

Primary outcomes:
measure: Determination of safety and tolerability of treatment with si-544
timeFrame: From Day -35 to Day 106
measure: Determination of safety and tolerability of treatment with si-544
timeFrame: From Day 1 (Baseline) to Day 106
Secondary outcomes:
measure: Determination of the plasma concentrations of free si-544
timeFrame: Day 1 (Baseline) and Day 25
measure: Determination of the pharmacodynamics (PD) of si-544 as assessed by the number of T cells in peripheral blood
timeFrame: From Day 1 (Baseline) to Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the pharmacodynamics (PD) of si-544 as assessed by immunophenotypes of T cell subsets
timeFrame: From Day 1 (Baseline) to Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the pharmacodynamics (PD) of si-544 as assessed by serum cytokine levels
timeFrame: From Day 1 (Baseline) to Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the immunogenicity of si-544 treatment
timeFrame: From Day 1 (Baseline) to Day 29 (Week 5) and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by psoriasis area and severity index (PASI)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by psoriasis area and severity index (PASI) response rate
timeFrame: At Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by physician's global assessment (PGA) of disease activity
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by body surface area (BSA)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by a numeric rating scale (NRS)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment as assessed by a numeric rating scale (NRS)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment on symptoms of psoriasis vulgaris (Ps) in Ps patients only as assessed by dermatological life quality index (DLQI)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment on symptoms of psoriatic arthritis (PsA) in PsA patients only as assessed by psoriatic arthritis quality of life (PsAQoL)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment on symptoms of psoriatic arthritis (PsA) in PsA patients only (assessment of pain)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment on symptoms of psoriatic arthritis (PsA) in PsA patients only as assesses by the 66 swollen joint count (SJC66)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
measure: Determination of the efficacy of si-544 treatment on symptoms of psoriatic arthritis (PsA) in PsA patients only as assessed by the 68 tender joint count (TJC68)
timeFrame: From Day 1 (Baseline) to Day 15, Day 29 (Week 5), Week 8, Week 12 and Week 16
Other outcomes:
Locations:
city: Bad Bentheim
country: Germany
facility: selectION Clinical Trial Site
city: Berlin
country: Germany
facility: selectION Clinical Trial Site
city: Blankenfelde-Mahlow
country: Germany
facility: selectION Clinical Trial Site
city: Hamburg
country: Germany
facility: selectION Clinical Trial Site
Study officials:
affiliation: selectION Therapeutics GmbH
name: Andreas Klostermann, Dr.
role: STUDY_DIRECTOR
References: