A Study to Evaluate the Effects of ASP5502 in Healthy Adults and Adults With Primary Sjögren's Syndrome

Phase

Condition

Dermatomyositis (Connective Tissue Disease)

Healthy Volunteers

Sjogren's Syndrome

Treatment

ASP5502

Placebo

Clinical Study ID

NCT06544642

5502-CL-0001

Ages 18-65
All Genders
Accepts Healthy Volunteers

Study Summary

Primary Sjögren's syndrome (pSS) is a condition when the body's immune system attacks glands that produce fluids, such as the tear and saliva glands. This leads to dry eyes and a dry mouth. However, other symptoms may occur such as fatigue, joint pain, and skin problems. These symptoms can be severe. Symptoms can be treated but there is an unmet need to treat the actual condition.

In this study, ASP5502 is being given to humans for the first time. The people taking part are healthy adults or adults with pSS. The main aims of the study are to check the safety of ASP5502 and how people tolerate ASP5502.

This study will be in 3 parts. In Part 1, healthy men and women will take tablets of ASP5502 or a placebo just once. In this study, the placebo looks like the ASP5502 tablet but doesn't have any medicine in it. Different small groups of people will take a lower to a higher dose of ASP5502 or a placebo. This will happen one group after another. One small group will take tablets of ASP5502 or placebo with and without food. This is to find out if food affects how the body processes ASP5502.

After their dose, people will stay in the medical center for a few nights. This is to have blood tests, electrocardiograms (ECGs) to check heart health, and other safety checks, and to report any medical problems. One of these checks is to have their heart continuously tracked during the first night. This is called telemetry. People who take tablets of ASP5502 or placebo with and without food will stay in the medical center for a few extra nights.

In Part 2, healthy men and women will take tablets of ASP5502 or a placebo. They will do this once a day for 2 weeks (14 days). Different small groups of people will take a lower to a higher dose of ASP5502 or a placebo. This will happen one group after another.

After taking ASP5502 or the placebo, people will stay in the medical center for a few nights. This is to have blood tests, ECGs to check heart health, and other safety checks, and to report any medical problems. Telemetry will also be done continuously during the first night.

In Part 3, men and women with pSS will take tablets of ASP5502. They will do this once a day for 4 weeks (28 days). Different small groups of people will take a lower to a higher dose of ASP5502. This will either happen for one group after another, or just for 1 group. The number of groups and the doses taken will be worked out from the results from Part 1 and Part 2 of this study. People will stay in the medical center for a couple of nights. This will happen for their first dose, then again after about 2 weeks and 4 weeks of treatment. As in Parts 1 and 2, this is to have blood tests, ECGs to check heart health, and other safety checks, and to report any medical problems.

In all parts of the study, people will return to the medical center about 1 week after their final blood sample is taken, for health check. People in parts 2 and 3 will also receive a telephone call safety check about 4 weeks after their last dose of ASP5502.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Inclusion Criteria for Healthy Participants

Participant is healthy and has no clinically significant medical conditions based onthe review of the physical examination, ECG and protocol-defined clinical laboratorytests at screening or on day -2 or day -1.
Female participant is not pregnant and at least 1 of the following conditions apply:
Not a women of childbearing potential (WOCBP)
WOCBP who has a negative blood pregnancy test at screening and a urinepregnancy test on day -2 and agrees to follow the contraceptive guidance fromthe time of informed consent through at least 5 half-lives or 30 days,whichever is longer, after final study intervention administration. Femaleparticipants on hormonal contraceptives must also be using a double barriermethod as defined in Contraceptive Requirements.
Female participant must not be breastfeeding or lactating starting at screening andthroughout the investigational period and for 5 half-lives or 30 days, whichever islonger, after final study intervention administration.
Female participant must not donate ova starting at first administration of studyintervention and throughout the investigational period and for 5 half-lives or 30days, whichever is longer, after final study intervention administration.
Male participant must agree to use contraception with female partner(s) ofchildbearing potential (including breastfeeding partner) throughout the treatmentperiod and for 5 half-lives or 30 days, whichever is longer, after final studyintervention administration.
Male participant must agree to remain abstinent or use a condom with pregnantpartner(s) for the duration of the pregnancy throughout the investigational periodand for 5 half-lives or 30 days, whichever is longer, after final study interventionadministration.
Male participant must not donate sperm during the treatment period and for 5half-lives or 30 days, whichever is longer, after final study interventionadministration.
Participant agrees not to participate in another interventional study whileparticipating in the present study from the time of signing informed consent throughthe end of study visit.
Participant has a body mass index (BMI) range of 18.5 to 30.0 kg/m^2 inclusive andweighs at least 50 kg for male and 40 kg for female at screening.

Inclusion Criteria for Participants with pSS

Participant is diagnosed based on the 2016 American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) Classification Criteriafor pSS. Diagnosis should have been established at least 6 months prior to day -1and no clinically significant medical condition is present on the physicalexamination, ECG and protocol-defined clinical laboratory tests at screening or onday -1.
Female participant is not pregnant and at least 1 of the following conditions apply:
Not a WOCBP
WOCBP who has a negative blood pregnancy test at screening and a urinepregnancy test on day -1 and agrees to follow the contraceptive guidance fromthe time of informed consent through at least 5 half-lives or 30 days,whichever is longer, after final study intervention administration. Femaleparticipants on hormonal contraceptives are allowed ONLY if the participantalso agrees to use a double barrier method (condom and spermicide) and theresults from the 4β hydroxycholesterol assessment in Part 2 are negative.
WOCBP must also be using a double barrier method as defined in ContraceptiveRequirements.
Female participant must not be breastfeeding or lactating starting at screening andthroughout the investigational period and for 5 half-lives or 30 days, whichever islonger, after final study intervention administration.
Female participant must not donate ova starting at first administration of studyintervention and throughout the investigational period and for 5 half-lives or 30days, whichever is longer, after final study intervention administration.
Male participant must agree to use contraception with female partner(s) ofchildbearing potential (including breastfeeding partner) throughout the treatmentperiod and for 5 half-lives or 30 days, whichever is longer, after final studyintervention administration.
Male participant must agree to remain abstinent or use a condom with pregnantpartner(s) for the duration of the pregnancy throughout the investigational periodand for 5 half-lives or 30 days, whichever is longer, after final study interventionadministration.
Male participant must not donate sperm during the treatment period and for 5half-lives or 30 days, whichever is longer, after final study interventionadministration.
Participant agrees not to participate in another interventional study whileparticipating in the present study from the time of signing informed consent throughthe end of study visit.
Participant has a BMI range of 18.5 to 30.0 kg/m^2 inclusive and weighs at least 50kg for male and 40 kg for female at screening.

Exclusion

Exclusion Criteria:

Exclusion Criteria for Healthy Participants

Participant has been pregnant within 6 months prior to screening.
Participant has any history or evidence of any clinically significantcardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic,metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/orother major disease or malignancy.
Participant has a history of malignancy within 2 years before screening (exceptionsare squamous and basal cell carcinomas of the skin and carcinoma in situ of thecervix, or malignancy that is considered cured with minimal risk of recurrence).
Participant has had major surgery (e.g., requiring general anesthesia) within 90days before screening, or will not have fully recovered from surgery, or has surgeryplanned during the time the participant is expected to participate in the study orwithin 5 half-lives after the last dose of study intervention administration or endof study visit, whichever is longer.
Participant has/had febrile illness or symptomatic, viral, bacterial (includingupper respiratory infection) or fungal (noncutaneous) infection within 28 days priorto day -1.
Participant has a positive QuantiFERON®-TB Gold test at screening.
Participant has a history of drug or alcohol abuse according to Diagnostic andStatistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 2 yearsbefore screening.
Participant has a history of unexplained syncope, cardiac arrest, unexplainedcardiac arrhythmias or torsades de pointes, structural heart disease, a familyhistory of long QT syndrome or taking any QT prolonging medication.
Participant has used any prescribed or nonprescribed drugs (including vitamins andnatural and herbal remedies, e.g., St. John's Wort) in the 28 days prior to studyintervention administration, except for contraceptive use, hormone replacementtherapy (HRT) use and occasional use of acetaminophen (up to 2 g/day).
Participant has used any inducer of metabolism (e.g., barbiturates and rifampin) inthe 3 months prior to day -1.
Participant has received a vaccine within the 2 weeks prior to day -1 or will have avaccine dose before the follow-up visit.
Participant has received any investigational therapy within 28 days or 5 half-lives,whichever is longer, prior to screening.
Participant has any of the liver safety monitoring panel (alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate aminotransferase [AST] and totalbilirubin [TBL]) above the upper limit of normal (ULN) on day -2. In such a case,the assessment may be repeated once.
Participant has creatinine level outside normal limits on day -2. In such a case,the assessment may be repeated once.
Participant has a mean pulse < 45 or > 90 bpm; mean systolic blood pressure > 140mmHg; mean diastolic blood pressure > 90 mmHg (measurements taken in triplicateafter participant has been resting in the supine position for at least 5 minutes;pulse will be measured automatically) on day -2. If the mean blood pressure exceedsthe limits above, 1 additional triplicate may be taken.
Participant has a mean corrected QT interval using Fridericia's correction formula (QTcF) of > 430 msec (for male participants) and > 450 msec (for femaleparticipants) on day -2. If the mean QTcF exceeds these limits, 1 additionaltriplicate ECG may be taken.
Participant tests positive for alcohol at screening or on day -2.
Participant tests positive for drugs of abuse (amphetamines, barbiturates,benzodiazepines, cocaine and opiates) at screening or on day -2.
Participant tests positive for cannabinoids on day -2.
Participant has a positive rapid coronavirus disease (COVID) antigen test on day -2.
Participant has a positive serology test for hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]), hemoglobin C (HBc) antibodies, hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiencyvirus (HIV) type 1 and/or type 2 at screening.
Participant has any condition which makes the participant unsuitable for studyparticipation.
Participant has a known or suspected hypersensitivity to ASP5502 or comparator orany components of the formulation used.
Participant has smoked, used tobacco-containing products or nicotine ornicotine-containing products (e.g., electronic vapes) within 6 months prior toscreening or the participant tests positive for cotinine at screening or day -2.
Participant has a history of consuming > 10 units for male or > 8 units for femaleparticipants of alcoholic beverages per week within 3 months prior to screening (note: 1 unit = 12 ounces of beer, 5 ounces of wine, 1.5 ounce of spirits/hardliquor).
Participant has used any drugs of abuse (e.g., amphetamines, barbiturates,benzodiazepines, cocaine and/or opiates) within 3 months prior to day -1.
Participant has had significant blood loss, donated >/= 1 unit (450 mL) of wholeblood or donated plasma within 7 days prior to day -1 and/or received a transfusionof any blood or blood products within 60 days.
Participant has had previous exposure with ASP5502.
Participant is an employee of Astellas, the study-related clinical researchorganizations (CROs) or the clinical unit.

Exclusion Criteria for Participants with pSS

Participant has been diagnosed with secondary Sjögren's syndrome or any othersystemic autoimmune disease (e.g. rheumatoid arthritis, systemic lupuserythematosus, multiple sclerosis).
Participant has severe complications of Sjögren's syndrome, such as neurologic orcardiac involvement, interstitial lung disease and severe myositis.
Participant is using immunosuppressant therapy (e.g., methotrexate, azathioprine,mycophenolate mofetil), B-cell depleting agents (e.g., rituximab, belimimab), Januskinase inhibitors (JAKi) (e.g., tofacitinib), calcineurin inhibitors (e.g.,tacrolimus, cyclosporin), and other biologics (e.g., abatacept, cyclophosphamide,leflunomide).
Participant receives corticosteroid therapy exceeding 10 mg prednisone equivalentsper day.
Participant has been pregnant within 6 months prior to screening.
Participant has any history or evidence of any not-related to pSS clinicallysignificant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic,immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric,renal and/or other major disease or malignancy.
Participant has a history of malignancy within 2 years before screening (exceptionsare squamous and basal cell carcinomas of the skin and carcinoma in situ of thecervix, or malignancy that is considered cured with minimal risk of recurrence).
Participant has had major surgery (e.g., requiring general anesthesia) within 90days before screening, or will not have fully recovered from surgery, or has surgeryplanned during the time the participant is expected to participate in the study orwithin 5 half-lives after the last dose of study intervention administration or endof study visit, whichever is longer.
Participant has/had febrile illness or symptomatic, viral, bacterial (includingupper respiratory infection) or fungal (noncutaneous) infection within 28 days priorto day -1.
Participant has a past history of serious opportunistic infections.
Participant has a positive QuantiFERON®-TB Gold test at screening.
Participant has a positive rapid COVID antigen test on day -1.
Participant has a history of drug or alcohol abuse according to DSM-5 criteriawithin 2 years before screening.
Participant has any of the liver safety monitoring panel (ALP, ALT, AST and TBL)above the ULN on day -1. In such a case, the assessment may be repeated once.
Participant has creatinine level outside normal limits on day -1. In such a case,the assessment may be repeated once.
Participant has a mean pulse < 45 or > 90 bpm; mean systolic blood pressure > 140mmHg; mean diastolic blood pressure > 90 mmHg (measurements taken in triplicateafter participant has been resting in the supine position for at least 5 minutes;pulse will be measured automatically) on day -1. If the mean blood pressure exceedsthe limits above, 1 additional triplicate may be taken.
Participant has a mean corrected QTcF of > 450 msec on day -1.
Participant has a history of unexplained syncope, cardiac arrest, unexplainedcardiac arrhythmias or torsades de pointes, structural heart disease or a familyhistory of long QT syndrome.
Participant is using QT prolongating medication such as antiarrhythmics (e.g.amiodarone, sotalol, ibutilide, dofitilide, disopyramide), antipsychotic (e.g.chlorpromazine, haloperidol), antidepressants (e.g. citalopram), antibiotics (e.g.sparfloxacin, ciprofloxacin, erythromycin, azithromycin, clarithromycin) orantiemetics (e.g. domperidone).
Participant has used any Cytochrome P450 (CYP) 3A4 inducer of metabolism (e.g.,barbiturates and phenytoin, barbiturates, carbamazepine, bosentan, felbamate,griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide,aprepitant and products containing St. John's wort) or HIV protease inhibitors, HCVprotease inhibitor or non-nucleoside reverse transcriptase inhibitors (e.g.,nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir,lopinavir/ritonavir, tipranavir/ritonavir, boceprevir, telaprevir and nevirapine)within 3 months prior to day -1.
Participant has used any narrow therapeutic index CYP3A4 substrate (e.g.,alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl,pimozide, quinidine, sirolimus, and tacrolimus) within 24 hours prior to day -1.
Participant has received a vaccine within the 2 weeks prior to first studyintervention administration or will have a vaccine dose before the follow-up visit.
Present or previous history of participation in a study of the study intervention.
Participant has received any investigational therapy within 28 days or 5 half-lives,whichever is longer, prior to screening.
Participant has any condition which makes the participant unsuitable for studyparticipation.
Participant has a known or suspected hypersensitivity to ASP5502 or any componentsof the formulation used.
Participant is an employee of Astellas, the study-related clinical researchorganizations (CROs) or the clinical unit.

Study Design