Healthy volunteers and patients with mild to moderate chronic plaque psoriasis Skin and Connective Tissue Diseases
Conditions
Interventions
Current intervention as of 20/11/2023:
Part A (Single-ascending-dose): A single dose of the monoclonal antibody AX-202 or a matching placebo (Sodium Chloride
0.9% NaCl) will be administered by intravenous infusion on Day 1. The starting dose in Cohort 1 is 0.5 mg/kg. Subsequent doses will be determined from the review of safety and Pharmacokinetic (PK) dat
0.9% NaCl) will be administered by intravenous infusion on Days 1, 22, 43 and 64. The planned starting dose of AX-202 to be administered in Part B Cohort 1 will be confirmed during the interim review
0.9% NaCl) will be administered by intravenous infusion on Day 1. The starting dose in Cohort 1 is 0.5 mg/kg. Subsequent doses will be determined from the review of safety and Pharmacokinetic (P
Sponsors
Arxx Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A 1. Subjects must have written informed consent obtained prior to any study-related procedures. 2. Subjects must be able to understand and comply with the requirements of the study, as judged by the Investigator. 3. Male and female subjects must be between 18-55 years inclusive, at the time of informed consent. 4. Female subjects must either be of non-childbearing potential or if of childbearing potential, must not be pregnant, breastfeeding or lactating and must use, with their partner, a condom with or without spermicide plus a highly effective birth control method from the time of informed consent and for 120 days following last administered dose. 5. Male subjects who are sexually active with a partner of childbearing potential must use, with their partner, a condom with or without spermicide plus an approved method of highly effective contraception from the time of informed consent and for 120 days following their last administered dose of IMP. 6. Subject must agree not to donate semen or ova/oocytes from consent and for 120 days after the last dose of IMP. 7. Subjects must have a Body Mass Index (BMI) = 18 and = 32 kg/m2 and weight of at least 45kg at screening. 8. Subjects must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator. Part B 1. Patients must have written informed consent obtained prior to any study-related procedures. 2. Patients must be able to understand and comply with the requirements of the study, as judged by the Investigator. 3. Male and female patients must be between 18-65 years inclusive, at the time of informed consent. 4. Patients must have a documented diagnosis of plaque psoriasis for = 6 months prior to screening. 5. Physicians Global Assessment (PGA) of 2/3 i.e. mild or moderate plaque psoriasis at baseline. 6. Body Surface Area (BSA) =2% and =10% at baseline. 7. A minimum of 2 psoriatic lesions of at least 2 cm x 2 cm at baseline, with at least 1 plaque in a site suitable for biopsy and be willing and able to undergo skin biopsies. 8. Female patients must either be of non-childbearing potential or if of childbearing potential, must not be pregnant, breastfeeding or lactating and must use, with their partner, a condom with or without spermicide plus a highly effective birth control method from the time of informed consent and for 120 days following last administered dose. 9. Male patients who are sexually active with a partner of childbearing potential must use, with their partner, a condom with or without spermicide plus an approved method of highly effective contraception from the time of informed consent until 120 days after their last dose of IMP. 10. Patients must agree not to donate semen or ova/oocytes during the study and for 120 days after the last dose of IMP. 11. Patients must have a Body Mass Index (BMI) = 18 and = 36 kg/m2 and weigh at least 45kg at screening. 12. Patients must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 03/03/2023: Part A 1. History/presence of any clinically relevant acute or chronic medical or psychiatric condition that could interfere with the subject’s safety or expose the subject to undue risk as judged by the Investigator. 2. Current or previous use of tobacco, nicotine products or e-cigarettes in the past 6 months. 3. Smoking history of > 5 pack years. 4. Positive urine cotinine test at screening or Day -1. Part B 1. History/presence of any clinically relevant acute or chronic medical or psychiatric condition other than psoriasis that could interfere with the patient’s safety or expose the patient to undue risk as judged by the Investigator. 2. A diagnosis of non-plaque psoriasis. 3. Plaque psoriasis restricted to the scalp, palms, soles and face. 4. Pustular, erythrodermic, inverse and guttate psoriasis. 5. Drug-induced psoriasis. 6. Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other immune-mediated conditions that are commonly associated with psoriasis for which a patient requires current systemic immunosuppressant medical treatment. 7. Presence of other skin conditions that could interfere with psoriasis evaluation or assessments. 8. Sunbed use in the 4 weeks prior to screening or planned use prior to the final study visit. 9. Any clinically significant infection requiring antimicrobial treatment in the 2 weeks prior to Day 1. Parts A & B 1. After a min 10 minutes supine rest at the time of screening or on Day -1: 1.1. Systolic blood pressure 140 mmHg, or 1.2. Diastolic blood pressure 90 mmHg, or 1.3. Pulse 90 bpm 2. Any clinically significant abnormalities in ECG at the time of screening or on Day -1 incl. prolonged QTcF (>450 ms for males; >470 ms for females) and cardiac arrhythmias, as judged by the Investigator. 3. Clinically significant abnormalities in renal function at screening including: eGFR 1.0 x ULN 4.2. Aminotransferases >1.0 x ULN 4.3. ALP >1.0 x ULN 5. Haemoglobin 14 units per week. 16. Positive urine drugs of abuse test and/or alcohol breath test at screening or on Day -1 that cannot be accounted for by concomitant medication in the opinion of the Investigator. 17. Receiving any of the prohibited
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 20/11/2023: Safety and tolerability in Part A/B of the study measured by monitoring AEs, physical examinations, infusion site assessments, changes in vital signs, clinical laboratory parameters and ECG throughout the study to the time points defined below: Physical Exams: Part A Screen, Days -1, 4, 100 Part B Screen, Days -1, 4, 22, 25, 43, 64, 67, 163 Vital signs: Part A Screen, Days -1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22, 57, 100 Part B Screen, Days -1-4 (pre, 24, 48, 72 hours), 8, 15, 22, 23, 25, 29, 43, 50, 64-67 (pre, 24, 48, 72 hours), 71, 78, 99, 141, 163 Clinical labs Part A Screen, Days 1-4, 8, 15, 22, 57, 100 Part B Screen, Days 1-4, 8, 15, 22, 23, 25, 29, 43, 50, 64, 65, 67, 71, 78, 99, 141, 163 ECG Part A Screen, Days -1-2 (pre, 0, 1, 24 hours), 15, 22, 57, 100 Part B Screen, Days -1-2 (pre, 0, 1, 24 hours), 15, 22, 23, 29, 43, 50, 64-65 (pre, 0, 1, 24 hours), 78, 99, 141, 163 _____ Previous primary outcome measures: Safety and tolerability in Part A/B of the study measured by monitoring AE’s, physical examinations, infusion site assessments, changes in vital signs, clinical laboratory parameters and ECG throughout the study to the time points defined below: Physical Exams: Part A Screen, Days -1, 4, 100 Part B Screen, Days -1, 4, 22, 25, 121 Vital signs: Part A Screen, Days -1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22, 57, 100 Part B Screen, Days -1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22-25(pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 29, 36, 57, 85, 121 Clinical labs Part A Screen, Days 1-4, 8, 15, 22, 57, 100 Part B Screen, Days 1-4, 8, 15, 22, 23, 25, 29, 36, 57, 85, 121 ECG Part A Screen, Days -1-2 (pre, 0, 1, 24 hours), 15, 22, 57, 100 Part B Screen, Days -1-2 (pre, 0, 1, 24 hours), 15, 22-23 (pre, 0, 1, 24 hours), 36, 57, 85, 121 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 20/11/2023: 1. Quantification of AX-202 in plasma will be performed followed by calculation of pharmacokinetic parameters, including but not limited to; Cmax, tmax, AUC (AUC [0-8], AUC [0-t]), and t1/2, CL, Vss. Dose and time dependency will be assessed for the pharmacokinetic parameters. In Part A, outcomes assessed on Days 1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22, 57, 100 and in Part B on Days 1-4 (pre, 0, 4, 8, 24, 48, 72 hours), 8, 15, 22, 43, 64-67 (pre, 0, 4, 8, 24, 48, 72 hours), 71, 78, 85, 99, 113, 141, 163 2. Antibodies to AX-202 in serum will be measured to evaluate immunogenicity in Part A on Days 1 (pre-dose), 22, 57, 100 and in Part B on Days 1 (pre-dose), 22 (pre-dose), 43 (pre-dose), 64 (pre-dose), 78, 141, 163 _____ Previous secondary outcome measures: 1. Quantification of AX-202 in plasma will be performed followed by calculation of pharmacokinetic parameters, including but not limited to; Cmax, tmax, AUC (AUC [0-8], AUC [0-t]), and t1/2, CL, Vss. Dose and time dependency will be assessed for the pharmacokinetic parameters. In Part A, outcomes assessed on Days 1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22, 57, 100 and in Part B on Days 1-4 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 8, 15, 22-25 (pre, 0, 1, 2, 4, 8, 24, 48, 72 hours), 29, 36, 57, 85, 121 2. Antibodies to AX-202 in serum will be measured to evaluate immunogenicity in Part A on Days 1 (pre-dose), 22, 57, 100 and in Part B on Days 1 (pre-dose), 22 (pre-dose), 36, 85, 121 | — |
Countries
England, United Kingdom
Contacts
Public ContactSylvia Vetrhus
Outcome results
None listed