Clinical trial NCT06444867: A Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of LEO 158968
Official title: An Open-label, Phase 1b, Multi-site Trial to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following a Single Dose of LEO 158968 in Subjects With Gout Flares
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Joint Pain
Gout Flares
Joint Inflammation
Keywords: LEO 158968
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2024-06-06
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate the effect on pain of a single, subcutaneous (SC) dose of LEO 158968 in participants with gout flares.


Eligibility criteria: Inclusion Criteria:

* Signed and dated informed consent has been obtained prior to any protocol-related procedures.
* Participants meeting the American College of Rheumatology (ACR/EULAR) 2015 gout criteria with a score ≥8.
* Presence of a gout flare for no longer than 96 hours prior to the baseline visit.
* In case of naïve or newly diagnosed participants, the presence of monosodium urate (MSU) crystals in synovial fluid will be evaluated and confirmed.
* At least 1 joint affected by acute gout (eg, ankle, foot, knee, toe). Participants may have oligoarticular gout, defined as \>1 and \<5 affected joints. However, participants with polyarticular gout are not eligible. In case the participant has more than one affected joint, the investigator should select the most symptomatic joint (most painful/with more inflammatory signs) for the study assessments (primary endpoint), and it will be identified as the 'index joint'.
* At screening and baseline (Day 1), a participant-reported joint pain at rest of ≥50 mm on a 0-100 mm VAS with pain intensity ≥2 using a 5-point Likert scale and at least 2 of the following criteria in the target joint:

  1. participant-reported flare.
  2. participant-reported warm joint.
  3. participant-reported swollen joint.
* Body mass index: ≤40 kg/m², at screening.
* Participants on ULT (xanthine oxidase inhibitors, uricosuric agents) with no changes in therapy for at least 2 weeks before dosing.
* Male participants, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from admission to the clinical research center until all follow-up procedures are complete. Adequate contraception for the male participant (and his female partner, if she is of childbearing potential) is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, a cervical cap, or a condom. Total abstinence from heterosexual intercourse, in accordance with the lifestyle of the participant, is also acceptable.
* Participants with hypertension, cardiovascular disease, diabetes, or renal disorder are required to be on a stable dose and schedule, with no changes in therapy for at least 4 weeks before screening and baseline, are expected to remain on a stable regimen during trial participation, and the diseases are biologically and clinically controlled.

Exclusion Criteria:

* Use of specified pain relief medications, including systemic glucocorticoids, within 4 weeks before the baseline visit, and weak and strong opioids, colchicine, and nonsteroidal anti inflammatory drugs within 7 days before the baseline visit.
* Presence of an acute gout flare in more than 4 joints at the baseline visit.
* Received a live vaccine within 4 weeks before dosing or receiving a live vaccine during the trial.
* Other causes of acute or chronic inflammatory arthritis (including rheumatoid arthritis, psoriatic arthritis, and calcium pyrophosphate deposition disease), tophaceous gout, or evidence/suspicion of infectious/septic arthritis.
* History of malignancy within the past 5 years, with the exception of basal cell skin cancer, carcinoma-in-situ of the cervix, or low-risk prostate cancer after curative therapy.
* Known hypersensitivity to any components of the product.
* Presence of active or recurrent bacterial, fungal, or viral infections within 15 days prior to the baseline visit, or presence of human immunodeficiency virus (HIV) infection, and hepatitis B and C infection.
* Presence of active or latent tuberculosis (to be determined by chest X-ray and a tuberculosis screening questionnaire).
* Uncontrolled clinically significant hematologic, pulmonary, endocrine, metabolic, gastrointestinal, central nervous system, or hepatic disease.
* Unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable angina, myocardial infarction, cerebrovascular events, or rapid atrial fibrillation) in the last 3 months prior to screening, or a cardiac hospitalization within the 3 months prior to screening.
* Participants who have undergone major surgery within 2 weeks before the baseline visit or have an unhealed operation wound.
* The presence of any medical or psychological condition or laboratory results that, in the Investigator's opinion, might create a risk to the participants or the trial.
* History of alcohol or substance abuse within the 12 months prior to the baseline visit or any condition associated with poor compliance as judged by the Investigator.
* Clinically significant general pain or non-gout-related joint pain that would interfere with the participant's ability to accurately assess pain in the target joint, at the discretion of the Investigator.
* Current participation in any other interventional clinical trial.

Primary outcomes:
measure: Number of Participants with a Patient-reported Pain Intensity Score of 0 or 1 as Assessed by the 5-point Likert Scale on Day 4
timeFrame: Day 4
Secondary outcomes:
measure: Number of Participants with a Patient-reported Pain Intensity Score of 0 or 1 as Assessed by the 5-point Likert Scale on Day 8
timeFrame: Day 8
measure: Number of Participants with a ≥2-point Reduction in Patient-reported Pain Intensity Score as Assessed by the 5-point Likert
timeFrame: Day 1 to Day 8
measure: Number of Participants Experiencing a Change in Pain Intensity in Affected Joints as Assessed by the Visual Analog Scale (VAS) Pain Score
timeFrame: Baseline to Day 8
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline to Day 85
measure: Number of Participants with LEO 158968 Anti Drug Antibodies (ADA) from Baseline to Day 85
timeFrame: Baseline to Day 85
measure: Number of Participants with LEO 158968 ADA from Baseline to Day 29
timeFrame: Baseline to Day 29
measure: Number of Participants Using Rescue Medications from Baseline to Day 8
timeFrame: Baseline to Day 8
Other outcomes:
Locations:
city: Lille
country: France
facility: LEO Pharma Investigational Site
city: Venlo
country: Netherlands
facility: LEO Pharma Investigational Site
city: London
country: United Kingdom
facility: LEO Pharma Investigational Site
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References: