| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Anti-Neutrophil Cytoplasmic Antibody associated vasculitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| ANCA-associated vasculitis |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Assess the pharmacokinetics (PK) of an exploratory pediatric liquid formulation of avacopan given under fasted and fed conditions compared to an avacopan capsule formulation given under fasted or fed conditions |
|
| E.2.2 | Secondary objectives of the trial |
| Assess the safety and tolerability avacopan capsule formulation given under fasted or fed conditions |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria will be confirmed at Screening and Period 1 Day 1
Male or female adults, 18 – 55 years of age, inclusive.
Body mass index is 18.5 to 32.0 kg/m2
Negative result of the human immunodeficiency virus (HIV) screen, the hepatitis B screen, the hepatitis C screen, and the QuantiFERON®-TB Gold test.
Negative result of SARS-CoV-2 test at Screening and Period 1 Day -1 and no symptoms consistent with COVID-19 infection for the previous 5 days prior to Day-1.
A female participant is eligible to participate if she is of: a. Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic sterilization, or postmenopausal defined as ≥12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] in the post-menopausal range is confirmatory). Documented verbal history from the participant is acceptable for all of the criteria stipulated above.
b) Child-bearing potential and agrees to use effective contraception methods listed in Appendix 1 from the signing of informed consent until 120 days after the last dose of study treatment.
c) Lactating but willing to stop breast feeding prior to the first dose of study treatment until 120 days after the last dose of study treatment.
Female participants must agree not to donate ova starting at Screening and for 120 days after the final study drug administration
Male participants must agree to use highly effective contraception methods listed in Appendix 1. This criterion must be followed from the time of the first dose of study treatment until 120 days after the last dose of study treatment.
Male participants must agree not to donate sperm starting from the time of the first dose of study treatment and for 120 days after the final study drug administration.
Judged by the Investigator to be otherwise fit for the study, based on medical history, physical examination, and clinical laboratory assessments. Participants with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to compromise participant participation in the study, may be entered into the study |
|
| E.4 | Principal exclusion criteria |
Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at Screening or at Period 1 Day -1, or women who desire to begin a family or to breastfeed during the full length of the study.
Expected requirement for use of any medication (with the exception of continued use by female subjects of hormonal contraceptives in accordance with a regimen that has been stable for at least the three months prior to Screening and post-menopausal females using estrogen replacement therapy) from Screening through the end of the study.
History within the 60 days prior to first administration of Investigational Product (IP) of use of cannabis or tobacco and/or nicotine-containing products.
History of drug abuse (either illicit or prescription) within two years prior to first administration of IP.
History of alcohol abuse at any time in the last five years from Screening.
History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
History or presence of any medical condition or disease of laboratory abnormality which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.
Donated or lost more than 50 mL of blood or blood products within 56 days prior to screening, or donated plasma within 7 days of randomization.
Hemoglobin less than the lower limit of normal or recent history (6 months prior to first dose) of iron deficient anemia.
Received a live vaccine within 4 weeks prior to screening.
Known hypersensitivity to avacopan or inactive ingredients of the avacopan capsules (including gelatin, polyethylene glycol, or Cremophor).
Participated in any clinical study of an investigational product within 30 days or 5 half-lives prior to randomization.
Subject has any evidence of hepatic disease; aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase, or bilirubin >1.5 x the upper limit of normal during screening and Day -1.
Subject has any evidence of renal impairment; serum creatinine >1.5 x upper limit of normal; eGFR <60 mL/min/1.73 m2 during screening and Period 1 Day-1.
Subject’s urine tested positive at Screening and/or on Period 1 Day -1 for any of the following: opioids, amphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, phencyclidine, or alcohol (Breathalyzer test allowed for alcohol).
Use of alcohol-, caffeine-, or xanthine-containing products within 1 week prior to Period 1 Day -1.
Subject has any evidence of gastro-intestinal disorder by exam or history (not including appendectomy or hernia) which could interfere with oral absorption, digestion, or uptake. Subjects with cholecystectomy should be excluded.
A symptomatic Covid-19 infection within the last 30 days prior to Screening and any continuing Covid-19 long haul symptomatology regardless of when the initial Covid-19 infection occurred.
Use of any prescription medications (with the exception of hormonal contraceptives and hormonal therapy), over-the-counter nonsteroidal anti-inflammatory drugs, herbal preparations, St. John’s Wort or consumption of grapefruit juice, grapefruit, or Seville oranges within 14 days before Period 1 Day 1 (first dose). Use of over-the-counter medications (other the nonsteroidal anti-inflammatory drugs), vitamins, or supplements (including omega-3 fish oils) within 7 days before Period 1 Day 1 (first dose). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PK parameters of Cmax, Tmax, AUClast, AUC0-72, and AUCinf |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Incidence of TEAEs and SAEs, as well as the clinical laboratory test results, ECG and
findings from physical examinations, and vital signs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | Yes |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Paediatric specific formulation (liquid formulation) vs capsules |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
| E.8.4 | Will this trial be conducted at multiple sites globally? | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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