Alpha-1 Antitrypsin Deficiency
Conditions
Interventions
Product Code: PHP-303
Pharmaceutical Form: Tablet
INN or Proposed INN: Not applicable
CAS Number: 1161921-82-9
Current Sponsor code: PHP-303
Other descriptive name: (4S)-4-[4-cyano-2-(methylsulfonyl)p
Sponsors
pH Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide signed and dated IEC-approved ICF prior to any study-related procedures and/or assessments being performed. 2. Willing and able to comply with protocol requirements, visit schedule, and protocol-stated restrictions for the duration of study participation. 3. Must agree to abstain from smoking and/or vaping from the time of screening through end of study. 4. Diagnosis of AATD as defined by serum AAT level 40 mL/min/1.73 m2 using the Cockcroft-Gault formula for creatinine clearance (weight should be corrected for BSA) 10. Has not received other forms of an experimental treatment (such as an investigational drug, new chemical entity and/or augmentation therapy) within a wash-out period of 5 half-lives of that treatment or 31 days, whichever is longer, and willing to forego such treatments for the duration of study participation. 11. All acute toxicities related to prior treatment recovered to Grade = 1. 12. A female participant must meet one of the following criteria as recommended by the Clinical Trial Facilitation Group: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) Participant is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a post-menopausal state (i.e., at least 1 year without menses prior to start of study drug). b. Participant is of childbearing potential If female of childbearing potential, negative serum pregnancy test performed within 7 days prior to start of study drug. WOCBP must use highly effective methods of contraception (defined as those resulting in a failure rate of < 1% per year when used consistently and correctly) from signing of ICF, through duration of study treatment and for at least 45 days after last dose of study drug. The contrace
Exclusion criteria
Exclusion criteria: A participant who meets any of the following criteria will be excluded from study participation and will not be enrolled: 1. Diffuse interstitial lung diseases, cystic fibrosis, or clinically significant bronchiectasis as determined by the Investigator. 2. Uncontrolled asthma as determined by the Investigator. a. Stable asthma, or past asthma diagnosis is not an exclusion criterion. 3. Acute exacerbation of underlying lung disease requiring oral steroids and/or antibiotics within 4 weeks of start of screening. If participants develop an acute exacerbation between screening and randomization, participants should not be randomized, and Screening should be disrupted. Participants may be rescreened when the acute exacerbation has stabilized or resolved. 4. Upper or lower respiratory tract infection within 4 weeks of start of screening. If participants develop an infection between screening and randomization, participants should not be randomized, and Screening should be disrupted. Participants may be considered for re-Screening, provided at least 2 weeks have lapsed since receiving last dose of antibiotics and provided their condition has stabilized. 5. Other acute illness within 4 weeks of start of screening. If participants develop an acute illness between screening and randomization, participants should not be randomized, and Screening should be disrupted. Participants may be considered for re-Screening, provided their condition has stabilized or resolved. When possible, Investigator is encouraged to contact the Medical Monitor to verify that participant can be re-screened. 6. Known seropositivity for HIV. 7. History of biopsy-proven cirrhosis or CT-evidence of possible cirrhosis, e.g., nodularity on CT, and/or clinical complications of cirrhosis (variceal bleeding, ascites, hepatic encephalopathy), and/or diagnosis of cirrhosis based on Investigator’s judgment. 8. History of pancreatitis. 9. Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology) a. Occult or prior hepatitis B infection (defined as positive total HBcAb and negative HBsAg) may be included. b. Treatment with IVIG within 3 months of enrollment. 10. Positive test results for hepatitis C (HCV antibody serology testing) with detectable HCV RNA by RT-PCR. a. Participants positive for HCV antibody are eligible only if RT-PCR is negative for HCV RNA. 11. Malignancy within the last 5 years. Exceptions include: a. Curatively treated basal cell/squamous cell skin cancer. b. Carcinoma in situ of the cervix. c. Superficial transitional cell bladder carcinoma. d. In situ ductal carcinoma of the breast after complete resection. e. Localized, resected and/or low-risk prostate cancer could be eligible; to be discussed with the Medical Monitor. 12. Smoked and/or vaped within 6 months prior to Screening. 13. Prior bone marrow or solid organ transplantation. 14. Expected to receive a lung or liver transplant during the course of the study. 15. Scheduled for lobectomy or lung volume-reduction surgery. 16. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. 17. Other major or uncontrolled medical conditions, e.g., myocardial infarction or NYHA Class III/IV heart failure within the last 6 months, stroke, uncontrolled diabetes, uncontrolled autoimmune disease, uncontrolled fun
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of PHP-303 20 mg QD versus PHP-303 10 mg QD versus placebo;Secondary Objective: To characterize the PK of PHP-303 20 mg QD versus PHP-303 10 mg QD;Primary end point(s): • Frequency, severity, and relatedness of TEAEs and SAEs • Changes from baseline in hematology and blood chemistry values • Assessments of physical examinations, vital signs, and ECGs ;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Levels of PHP-303 in sputum and plasma during treatment;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Information Desk
pH Pharma Inc.
Outcome results
None listed