Phase III, Efficacy and Safety of "Kamada-AAT for Inhalation"

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-65
SponsorKamada, Ltd.

About this trial

The goal of this clinical trial is to learn if AAT for inhalation, at a dose of 80 mg/day can slow the progression of lung disease in people who have lung disease caused by severe genetic deficiency in Alpha 1 Antitrypsin (AATD).

The main question it aims to answer is:

• Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung function worsening ? Lung function will be measured by spirometry.

Other questions it aims to answer are:

* Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung density loss ? Lung density will be measured by a CT scan. * Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung disease from worsening ? Lung disease will be measured using spirometry, lung volume, gas diffusion, six minute walk test, quality of life questionaires and biomarkers. * What medical problems do participants have when taking AAT for inhalation 80 mg/day daily ? Researchers will compare AAT for inhalation to a placebo (a look-alike substance that contains no drug) to see if AAT for inhalation works to treat AAT-deficiency related lung disease. Study participants will receive either AAT for inhalation or placebo for the first two years of the study. During the third and fourth years of the study all participants will receive AAT for inhalation regardless of which drug they received during the first two years.

Participants will:

* Inhale the study drug every day * Clean and disinfect the nebulizer every day * Document daily symptoms and study drug use in an electronic diary * Visit the clinic for tests and assessments. There are 11 clinic visits during the first two years of the study and 5-6 clinic visits during the third and fourth year, combined. After treatment ends, participants will visit the clinic 3 times in half a year.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes.

Serum AAT levels ≤ 11 µM at screening.

Lung disease with clinical evidence of airflow limitation (post bronchodilator FEV1/SVC≤70%) at screening.

40% ≤ FEV1 ≤ 80% of predicted post-bronchodilator at screening.

Disqualifiers

Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels < 0.05 g/L.

History of life-threatening transfusion reaction(s), allergy, anaphylactic reaction, or systemic response to human plasma-derived products.

Two or more moderate or any severe exacerbation(s) within the year prior to baseline.

A moderate exacerbation within 6 weeks prior to baseline.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Alpha 1-Antitrypsin

    Drug

    Kamada's alpha 1-antitrypsin product given by inhalation using the eFlow® electronic nebulizer manufactured by PARI Pharma GmbH

  • Placebo

    Drug

    Preparation of NaCl in phosphate buffer solution with 0.01% TWEEN-80

Treatment groups

220 Participants
are divided into 2 treatment groups
Group A: Inhaled AATActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

FEV1 post bronchodilator

Change from baseline in post bronchodilator FEV1 at 104 weeks

Time frame
104 weeks

Secondary outcomes

1

CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).

Change from baseline over 104 weeks of treatment in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).

Time frame
104 weeks
2

FEV1 % of predicted

Change from baseline over 104 weeks of treatment in FEV1 % of predicted

Time frame
104 weeks
3

FEV1/FVC %

Change from baseline over 104 weeks of treatment in FEV1/FVC %

Time frame
104 weeks
4

Exacerbations

Annual rate of exacerbations by severity and duration

Time frame
104 weeks

Other outcomes

1

TEAEs

Rate and severity of adverse events during treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs) and serious adverse events (SAEs) during treatment and follow-up period \[Safety Outcome\]

Time frame
130 weeks
2

PiM

Plasma M-type AAT specific (PiM) levels evaluated as function of exposure time, antibody response (positive vs. negative), and antibody titers. \[Safety Outcome\]

Time frame
130 weeks
3

ADA/nADA

Rate and titers of binding and neutralizing AAT antibodies (ADA/nADA) in plasma \[Safety Outcome\]

Time frame
130 weeks
4

ECG

Electrocardiogram \[Safety Outcome\] will be classified as normal or abnormal.

Time frame
130 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Kamada, Ltd.

Lead sponsor

Syneos Health

Collaborator