Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency

Completed · Phase 2 · Has a placebo group

Conditions studied: Alpha-1 Antitrypsin Deficiency (AATD), Pi*ZZ, Pi*SZ, Pi*Null, Another Rare Phenotype/Genotype Known to be Associated With Either Low or Functionally Impaired AAT Including F or I Mutations, Emphysema or COPD

In brief

This is a Phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH966) in subjects with confirmed AATD defined as Pi\*ZZ, Pi\*SZ, Pi\*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level \<11 μM or \<57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.

Key facts

Study ID

NCT03679598

Run by

University of Alabama at Birmingham

People needed

63

Starts

2019-04-08

Expected to finish

2023-12-01

Last updated by the study team

2024-08-20

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants are eligible to be included in the study only if ALL of the following criteria apply:
• Capable of giving signed informed consent as described in Appendix 3, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol
• Age ≥18 and ≤80 years
• Patients with a confirmed diagnosis of AATD: Pi*ZZ, Pi*SZ, Pi*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level <11 μM or <57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.
• FEV1 ≥25% predicted
• Patients will be eligible if they are either a) are not currently receiving augmentation treatment and have not received augmentation in the 12 weeks prior to screening or b) have received weekly infusions of augmentation at 60 mg/kg for at least 12 weeks prior to screening and intend to continue augmentation through the study period.
• Male or female sex a. Male participants must agree to use a highly effective contraception as detailed in Appendix 5 during the treatment period and for at least 4 days after the last dose of study treatment and refrain from donating sperm during this period b. Female participants are eligible to participate if not pregnant; not breastfeeding; and at least one of the following conditions is met: i. Not a woman of childbearing potential as defined in Appendix 5 OR ii. A woman of childbearing potential who agrees to follow the contraceptive guidance in Appendix 5. During the treatment phase and for at least 4 days after the last dose of study medication.

You may not qualify if…

• Participants are excluded from the study if ANY of the following criteria apply:
• Excluded Medical Conditions
• Subjects with Pi*MZ, Pi*FM, Pi*MS, Pi*SS, or other AATD phenotypes/genotypes not known to be independently associated with emphysema.
• Any clinically diagnosed lung disease other than COPD such as diffuse interstitial lung diseases, cystic fibrosis, or clinically significant bronchiectasis as determined by the Investigator
• Acute exacerbation of underlying lung disease requiring oral steroids and/or antibiotics within 4 weeks of baseline
• Acute or chronic hepatitis, including hepatitis B, hepatitis C (positive serologies, including hepatitis B and C antibody)
• HIV infection or other immunodeficiency or with an absolute neutrophil count ≤1.0 × 109/L
• Abnormal liver biochemistry (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase) >1.5 × upper limit of normal or total bilirubin > upper limit of normal (unless Gilbert's disease with normal conjugated bilirubin)
• Any of the following laboratory abnormalities are present at baseline:
• Platelet count <150×109/L
• Serum albumin ≤ 3.5 g/dL
• INR ≥1.2
• CPK ≥ ULN.
• History or current evidence of cirrhosis (on biopsy or imaging), esophageal varices, ascites or hepatic encephalopathy.
• Evidence of other forms of chronic liver disease based on diagnostic testing as per the guidelines (i.e. autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Hemochromatosis or iron overload).
• Patients with nonalcoholic fatty liver disease (NAFLD) as diagnosed by any imaging modality (or use of drugs associated with NAFLD for more than 2 weeks in the year prior to screening).
• Subjects with a history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening, defined as average of >20g/ day in female subjects and >30g/ day in male subjects.
• Fibrosis-4 (FIB-4) score >3.25
• Any of the following cardiovascular conditions within 6 months prior to the screening visit:
• Myocardial infarction or unstable angina
• Coronary artery bypass surgery, balloon angioplasty, percutaneous coronary intervention, or carotid revascularization procedure
• Uncontrolled hypertension
• Stroke or transient ischemic attack
• Congestive heart failure (New York Heart Association III/IV) with left ventricular ejection fraction < 40%
• Any clinically significant 12-lead electrocardiogram abnormalities at screening or baseline, including corrected QT interval by Fridericia's correction method >450 ms or history of significant cardiac dysrhythmia, including long QT syndrome

Where it is running

• The University of Alabama at Birmingham Lung Health Center — Birmingham, Alabama, United States
• UCLA — Los Angeles, California, United States
• National Jewish Health — Denver, Colorado, United States
• Columbia University — New York, New York, United States
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Temple University — Philadelphia, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• The University of Texas Health Science Center at Tyler — Tyler, Texas, United States
• University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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