A Multi-Center, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety and Tolerability of the Neutrophil Elastase Inhibitor PHP-303 in Adults with Alpha-1 Antitrypsin Deficiency (AATD)
- Conditions
- Alpha-1 Antitrypsin DeficiencyTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2019-002501-22-GB
- Lead Sponsor
- pH Pharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
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 < 11 µM (0.5 g/L) by documentation or by testing during Screening.
5.Pi*ZZ phenotype/genotype or Pi*Null phenotype/genotype by historical documentation or by testing during Screening. Other genotypes may be considered after discussion with the Medical Monitor.
6.Male or female participants = 18 years of age at the time of signing the ICF.
7.Diagnosis of emphysema confirmed by historical CT scan.
8.Post bronchodilator FEV1 = 35% of predicted during Screening (the FEV1 assessment can be repeated for confirmation purposes during Screening, provided the spirometry maneuvers are assessed as not meeting ATS/ ERS criteria as determined by the Investigator). FEV1 prior to randomization on dosing day (Day 1) must be = 35% predicted. If below 35%, Investigator should determine if there is a medical reason for deterioration. Such participants may be re-screened when stable.
9.Adequate bone marrow, cardiac, liver, pancreatic, and renal function, as assessed by the following laboratory requirements to be conducted within 14 days prior to start of study drug (laboratory test(s) that do not meet the criteria can be repeated a single time during Screening):
a.Hemoglobin = 9.0 g/dL
b.absolute neutrophil count (ANC) = 1500/?L
c.Platelet count = 100,000/?L
d.Total bilirubin < 1.3 mg/dL; participants with Gilbert’s syndrome may be enrolled with a total bilirubin = 3.0 × ULN
e.ALT and AST = 2 ULN, serum creatinine = 1.5 ULN
f.PT-INR and PTT = 1.5× ULN
g.Amylase/lipase WNL
h.Creatinine phosphokinase – WNL
i.Serum troponin I and T - WNL if tested in participants with elevated CPK MB fraction
j.Calculated GFR > 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method