Palmoplantar Pustulosis MedDRA version: 20.0 Level: LLT Classification code 10050185 Term: Palmoplantar pustulosis System Organ Class: 100000004858
Conditions
Interventions
Product Code: RIST4721
Pharmaceutical Form: Oral solution
INN or Proposed INN: RIST4721
CAS Number: 1418112-77-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentrati
Sponsors
Aristea Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria at the screening and Day –1 visits, unless specified otherwise: 1. Male or female subject, aged 18–70 years at the time of consent. 2. Subject has at least a 6-month history of PPP as defined by the presence of pustules on palms and/or soles, but without evidence of infection on palms and soles (information obtained from medical chart or subject’s physician, or directly from the subject). 3. Subject has moderate or severe PPP, as defined by PPPASI =8 and PPPGA =3 at Day –1, and a minimum of 8 fresh pustules at screening (fresh pustule count on both right/left palms and soles) and 20 fresh pustules at Day –1 (fresh pustule count on both right/left palms and soles). 4. Subject who wants to use an emollient should agree to use the same emollient, at the same frequency of application for 7 days before Day –1 and throughout the study. Note: However, on the day of scheduled visits, subjects cannot apply emollient before their scheduled visit time. 5. For female subject of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective contraceptive method, from at least 4 weeks before Day –1 until at least 4 weeks after the last study drug administration. Highly effective contraceptive methods include hormonal contraceptives (combined oral contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine systems, male partner(s) vasectomy, tubal ligation, or a double-barrier method of contraception (barrier methods include male condom, female condom, cervical cap, diaphragm, and contraceptive sponge) in conjunction with spermicide. Note: Subjects who are on a hormonal contraceptive must have been on a stable dose for at least 4 weeks before Day –1. Note: The above list of contraceptive methods does not apply to subjects who are abstinent for at least 4 weeks before Day –1 and will continue to be abstinent from penile - vaginal intercourse throughout the study. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Note: For countries where double-barrier methods are not accepted as highly effective contraception, then this option must not be considered. Note: A female of nonchildbearing potential is defined as follows: – Female who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy). – Female who has had a cessation of menses for at least 12 months without an alternative medical cause, and a follicle-stimulating hormone (FSH) test confirming nonchildbearing potential (refer to laboratory reference ranges for confirmatory levels). 6. Female subject of childbearing potential has a negative serum pregnancy test at screening and negative urine pregnancy test at Day –1. 7. Female subject agrees to not have egg retrieval during the study and for 1 month after the last study drug administration. 8. Male subject agrees to use condom and spermicide from Day –1 until at least 3 months after the last study drug administration. 9. Male subject agrees not to donate sperm during the study and for 3 months after the last study drug administration. 10. Subject has negative tuberculosis (TB) infection test. Subject will be evaluated for latent TB infection with a purified prot
Exclusion criteria
Exclusion criteria: 1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study. 2. In the opinion of the investigator performing the initial examination, the subject should not participate in the trial (eg, due to probable noncompliance or inability to understand the nature, meaning, and consequences of the trial, and give adequately informed consent). 3. Subject has evidence of erythrodermic, generalized pustular psoriasis, predominantly guttate psoriasis, or drug induced psoriasis. 4. Subject has a history of skin disease or presence of skin condition (except psoriasis) that, in the opinion of the investigator, would interfere with the study assessments. 5. Subject has moderate to severe psoriasis, as defined by plaque psoriasis covering =10% of his/her total BSA at Day –1. 6. Subject is known to have immune deficiency or is immunocompromised. 7. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day –1. Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or successfully treated localized carcinoma in situ of the cervix are not to be excluded. 8. Subject had a major surgery within 8 weeks prior to Day –1 or has a major surgery planned during the study. 9. Subject has any clinically significant medical condition or ECG/physical/laboratory/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results. 10. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). 11. Any clinically significant history of infection (except for localized herpes simplex) within 4 weeks prior to Day –1. 12. Subject has absolute neutrophil count ?1.8 x 109/L at screening. 13. Subject has ALT, AST or total bilirubin values =2 times the upper limit of normal (ULN), or other clinical evidence of significant hepatic impairment (eg, ascites, peri-umbilical veins, oesophageal varices) at screening. 14. Subject has a history of clinically significant anemia or Hgb value =10 g/dL at screening. 15. Subject has a creatinine clearance =60 ml/min at screening (calculated with MDRD formula). 16. Subject has used any topical medication to treat PPP, including corticosteroids, retinoids, vitamin D analogues (such as calcipotriol), or tar, within 2 weeks prior to Day –1. 17. Subject has used topical dapsone within 2 weeks prior to Day –1. 19. Subject has used strong systemic cytochrome P450 3A4/5 inhibitors or inducers within 4 weeks or 5 half-lives, whichever is longer, prior to baseline (Day –1) (topical cytochrome P450 3A4/5 inducers or inhibitors with known limited systemic availability may be permitted). Examples of strong systemic cytochrome P450 3A4/5 inhibitors or inducers are provided in Table 3. 20. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser within 4 weeks prior to Day –1. 21. Subject has had PUVA treatment within 4 weeks prior to Day –1. 22. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day –1. 23. Subject is currently receiving a nonbiological investigational product or investigational device or has received one within 4 weeks prior to Day –1. 24. Subject had excessive sun exposure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is: • To assess the efficacy of RIST4721 versus placebo in adult subjects with moderate to severe palmoplantar pustulosis (PPP) using a range of efficacy endpoints ;Secondary Objective: The secondary objective is: • To assess the safety of RIST4721 versus placebo in adult subjects with moderate to severe PPP ;Primary end point(s): Primary Efficacy Endpoints: • Relative change from baseline in fresh pustule count at Day 28 • Relative change from baseline in total pustule count at Day 28;Timepoint(s) of evaluation of this end point: EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • Absolute change from baseline in fresh pustule count at Day 28 • Absolute change from baseline in total pustule count at Day 28 • Proportion of subjects achieving at least a 50% reduction in fresh pustule count at Day 28 • Proportion of subjects achieving at least a 50% reduction in total pustule count at Day 28 Secondary Safety Endpoints: • Incidence of TEAEs • Changes in vital signs, ECG, and laboratory tests Exploratory Endpoints: • Absolute change from baseline in fresh pustule count at Day 7, Day 14, and Day 21 • Relative change from baseline in fresh pustule count at Day 7, Day 14, and Day 21 • Absolute change from baseline in total pustule count at Day 7, Day 14, and Day 21 • Relative change from baseline in total pustule count at Day 7, Day 14, and Day 21 • Proportion of subjects achieving a 50% reduction in fresh pustule count at Day 7, Day 14, and Day 21 • Proportion of subjects achieving a 75% reduction in fresh pustule count at Day 7, Day 14, Day 21, and Day 28 • Proportion of subjects achieving a 50% reduction in total pustule count at Day 7, Day 14, and Day 21 • Proportion of subjects achieving a 75% reduction in total pustule count at Day 7, Day 14, Day 21, and Day 28 • Absolute change from baseline in PPPASI at Day 7, Day 14, Day 21, and Day 28 • Relative change from baseline in PPPASI at Day 7, Day 14, Day 21, and Day 28 • Proportion of subjects achieving a PPPASI-50 at Day 7, Day 14, Day 21, and Day 28 • Proportion of subjects achieving a PPPASI-75 at Day 7, Day 14, Day 21, and Day 28 • Absolute change from baseline in PPPGA at Day 7, Day 14, Day 21, and Day 28 • Relative change from baseline in PPPGA at Day 7, Day 14, Day 21, and Day 28 • Proportion of subjects achieving a PPPGA of clear (0) or almost clear (1) with a 2-point decrease at Day 7, Day 14, Day 21, and Day 28 • Proportion of subjects achieving at least a 2-point decrease i | — |
Countries
Canada, Germany
Contacts
Public ContactClinical Trial Manager
bioskin GmbH
Outcome results
None listed