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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 19 December 2023
Main ID:  NCT03679598
Date of registration: 18/09/2018
Prospective Registration: Yes
Primary sponsor: University of Alabama at Birmingham
Public title: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency ATALANTa
Scientific title: A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan Disease
Date of first enrolment: April 8, 2019
Target sample size: 63
Recruitment status: Completed
URL:  https://clinicaltrials.gov/ct2/show/NCT03679598
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).  
Phase:  Phase 2
Countries of recruitment
United States
Contacts
Name:     Mark T Dransfield, MD
Address: 
Telephone:
Email:
Affiliation:  University of Alabama at Birmingham
Key inclusion & exclusion criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if ALL of the following criteria
apply:

1. 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

2. Age =18 and =80 years

3. 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.

4. FEV1 =25% predicted

5. 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.

6. 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.

Exclusion Criteria:

Participants are excluded from the study if ANY of the following criteria apply:

Excluded Medical Conditions

1. Subjects with Pi*MZ, Pi*FM, Pi*MS, Pi*SS, or other AATD phenotypes/genotypes not known
to be independently associated with emphysema.

2. 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

3. Acute exacerbation of underlying lung disease requiring oral steroids and/or
antibiotics within 4 weeks of baseline

4. Acute or chronic hepatitis, including hepatitis B, hepatitis C (positive serologies,
including hepatitis B and C antibody)

5. HIV infection or other immunodeficiency or with an absolute neutrophil count =1.0 ×
109/L

6. 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)

7. Any of the following laboratory abnormalities are present at baseline:

1. Platelet count <150×109/L

2. Serum albumin = 3.5 g/dL

3. INR =1.2

4. CPK = ULN.

8. History or current evidence of cirrhosis (on biopsy or imaging), esophageal varices,
ascites or hepatic encephalopathy.

9. 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).

10. 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).

11. 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.

12. Fibrosis-4 (FIB-4) score >3.25

13. Any of the following cardiovascular conditions within 6 months prior to the screening
visit:

1. Myocardial infarction or unstable angina

2. Coronary artery bypass surgery, balloon angioplasty, percutaneous coronary
intervention, or carotid revascularization procedure

3. Uncontrolled hypertension

4. Stroke or transient ischemic attack

14. Congestive heart failure (New York Heart Association III/IV) with left ventricular
ejection fraction < 40%

15. 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

16. History of cancer within the last 5 years, except for well-treated basal cell
carcinoma and squamous cell carcinoma of the skin

17. Other documented comorbidities or laboratory abnormalities that in the opinion of the
Investigator could affect the outcome of the study assessments, participant safety, or
ability of the participant to comply with the requirements of the protocol

Excluded Prior/Concomitant Therapy

18. Daily use of prednisone (>10mg daily), or other systemic glucocorticoids at comparable
or higher equivalent dose, or use of other immunosuppressant therapies are prohibited

19. Immunomodulating monoclonal antibodies within 6 months prior to screening are
prohibited

20. Daily use of non-steroidal anti-inflammatory drugs (NSAIDs) is prohibited. Daily use
of acetaminophen up to 2 g per day and aspirin up to 325 mg per day is permitted.

21. Initiation of drugs known for hepatotoxic potential within the 28 days prior to
screening including but not limited to: statins, NSAIDS, amoxicillin/clavulanate, PDE
inhibitors (theophylline, roflumilast), and anti-epileptics. Subjects on established
treatment for more than 28 days prior to screening will not be excluded. Requirement
for medications mainly metabolized by CYP2C9 and with narrow therapeutic index (eg,
warfarin, phenytoin) is prohibited

Excluded Prior/Concurrent Clinical Study Experience

22. Participation in any clinical investigation using medical devices or non-biologic
treatments within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to
the initial dosing (or longer if required by local regulations) is prohibited

23. Participation in any clinical investigation using biologic treatment within 6 months
of screening is prohibited

24. Previous participation in a gene therapy study for AATD at any time is prohibited

Other Exclusions

25. History of hypersensitivity to alvelestat (MPH966) or any of its e



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All
Health Condition(s) or Problem(s) studied
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
Alpha-1 Antitrypsin Deficiency (AATD)
Emphysema or COPD
Intervention(s)
Other: Placebo
Drug: Alvelestat (MPH966)
Primary Outcome(s)
Within-individual % change in plasma desmosine/isodesmosine [Time Frame: baseline, week 12]
Numbers and % of subjects who experience at least 1 treatment-emergent adverse event [Time Frame: baseline, week 16]
Secondary Outcome(s)
Secondary ID(s)
IRB-300002338
4UH3TR002450-02
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Institutes of Health (NIH)
Mereo BioPharma
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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