A first-in-human single and multiple ascending dose study of AX-202
- Conditions
- Healthy volunteers and patients with mild to moderate chronic plaque psoriasisSkin and Connective Tissue Diseases
- Registration Number
- ISRCTN79668046
- Lead Sponsor
- Arxx Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 58
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.
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 <90 or >140 mmHg, or
1.2. Diastolic blood pressure <50 or >90 mmHg, or
1.3. Pulse <40 or >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 <60 mL/min
4. Clinically significant abnormalities in liver function at screening including:
4.1. Bilirubin >1.0 x ULN
4.2. Aminotransferases >1.0 x ULN
4.3. ALP >1.0 x ULN
5. Haemoglobin <130 g/l for males or <120 g/l for females at screening
6. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first dose of IMP.
7. Malignancy within the past 5 years of screening with the exception of in situ removal of basal cell carcinoma or resected benign colonic polyps.
8. Any planned major surgery within the duration of the study or in the 30 days following study completion.
9. History of latent or active tuberculosis or a positive Quantiferon test at screening. Patients with an indeterminate result at screening will be allowed one retest; if not negative on retesting, the subject will be excluded.
10. Females who are pregnant, breastfeeding, lactating or plan to be pregnant during the study period or 120 days after.
11. Female subjects with a positive serum or urine pregnancy test at screening or on Day -1.
12. Positive serum HBsAg, HCVAb or HIV 1 and/or 2 antibodies at screening.
13. A Positive test for active COVID-19 prior to dosing on Day 1.
14. History of any drug and/or alcohol abuse in the 2 years prior to screening.
15. Regular alcohol consumption of >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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method