A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03591926
• Date of registration: 09/07/2018
• Prospective Registration: No
• Primary sponsor: Samumed LLC
• Public title: A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Scientific title: A Phase 2a, 24-Week, Multi-Center, Open-Label Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Date of first enrolment: January 1900
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03591926
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Australia, New Zealand

Contacts

• Name: Yusuf Yazici, M.D.
• Affiliation: Samumed LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- IPF diagnosis within 5 years of study start based upon thoracic society guidelines and
confirmed by Investigator at study start

- Able to walk > 150 m in 6 Minute Walk Test without the use of supplemental oxygen at
study start

- Has a life expectancy of at least 12 months in the opinion of the Investigator

- Full understanding of the requirements of the study and willingness and ability to
comply with all study visits and procedures

- Able to comprehend and willing to sign an informed consent form (ICF) prior to any
study-related procedure being performed

- Able to tolerate and complete placebo (vehicle) inhalation for 10 minutes without
experiencing a significant cough, in the opinion of the Investigator

- Subjects currently treated with pirfenidone or nintedanib must be willing to remain on
their current treatment for the duration of the protocol, unless they experience rapid
progression, or if, in the opinion of the Investigator, treatment adjustments are
necessary

Exclusion Criteria:

- Women who are pregnant or lactating

- Women of childbearing potential who are sexually active and are not willing to use an
appropriate method of birth control during the study treatment period until 90 days
post study medication administration

- Males who are sexually active and not willing to use a condom, and have a partner who
is capable of becoming pregnant, if neither has had surgery to become sterilized,
and/or who are not willing to use an appropriate method of birth control during the
study treatment period until 90 days post study medication administration

- Males unwilling to refrain from sperm donation during the study treatment period until
90 days post study medication administration

- Subjects unwilling to refrain from blood and plasma donation during the study
treatment period until 90 days post study medication administration

- A history of abuse of prescription or illicit drugs within 6 months prior to study
start

- Positive urine drug and alcohol screen with the exception of positive findings related
to current prescription therapy at study start

- Occurrence of serious illness requiring hospitalization within 90 days prior to study
start

- Presence of active infections at study start

- Current smoker or past history of smoking (e.g., cigarettes, e-cigarettes, pipes,
cigars) within 6 months of study start or >50 pack years

- Use of non-inhaled tobacco- or nicotine-containing products (e.g., chewing tobacco,
nicotine gum, lozenges, or patches) within 30 days prior to study start until
completion of the study

- Regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for
males (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces
[45 mL] of hard liquor) within 30 days prior to study start until completion of the
study

- Lung transplantation anticipated during the duration of the trial

- Subjects receiving treatment with pirfenidone or nintedanib that:

1. Have been on treatment for less than 12 weeks prior to study start

2. Have not been on a stable dose for at least 30 days prior to study start

- Subjects who are not currently on but have previously received pirfenidone or
nintedanib that have not been off of pirfenidone or nintedanib for at least 30 days
prior to study start

- Receipt of any of the following medication or treatment prior to study start:

1. N-acetylcysteine prescribed for the treatment of IPF within 30 days prior to
study start

2. Previous therapeutic radiation treatment of the lungs, mediastinum, or chest wall

3. Participation in a clinical research trial that included the receipt of an
investigational product or any experimental therapeutic procedure within 30 days
or 5 half-lives of the investigational product (if known), whichever is longer,
prior to study start

4. Immunosuppressive medications [e.g., methotrexate, cyclosporine, azathioprine,
systemic or inhaled glucocorticosteroids with the exception of short term use of
systemic glucocorticosteroids less than or equal to 10 mg of prednisone daily (or
equivalent) for a non-IPF condition such as an allergic reaction or rash] within
8 weeks prior to study start

5. Use of any therapy targeted to treat IPF (including but not limited to
d-penicillamine, endothelium receptor antagonist [e.g., bosentan, ambrisentan],
and interferon gamma-1B) within 30 days prior to study start

6. Use of any cytokine modulator (etanercept, adalimumab, efalizumab, infliximab,
golimumab, certolizumab, rituximab) within 90 days or 5 half-lives, whichever is
longer, prior to study start

7. A bronchodilator used within 1 week of study start

8. SM04646

- A "bronchodilator response" at study start, defined by an absolute increase of = 12%
and an increase of 0.2 L in FEV1 or FVC, or both, after bronchodilator use compared
with the values before bronchodilator use

- History of any of the following conditions:

1. Pulmonary embolism or pulmonary hypertension

2. Creatinine clearance of less than 50mL per minute

3. Active tuberculosis (TB) infection or history of incompletely treated latent TB
infection

4. History of malignancy within the last 5 years; however, the following subjects
are eligible:

1. Subjects with prior history of in situ cancer or basal or squamous cell skin
cancer that has been completely excised

2. Subjects with other malignancies if they have been continuously disease free
for at least 5 years prior to any study drug administration

3. Subjects with prostate cancer followed by surveillance.

5. Any connective tissue disease, including but not limited to scleroderma, systemic
lupus erythematosus, rheumatoid arthritis, and polymyositis/dermatomyositis

6. Congenital respiratory conditions (e.g., cystic fibrosis)

7. Chronic obstructive pulmonary disease (COPD) or asthma

8. Current or recent respiratory tract infection (e.g., pneumonia, purulent
bronchitis, or viral upper respiratory tract infection) within 30 days prior to
study start

9. Acute exacerbation of IPF, in the opinion of the


Age minimum: 40 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: SM04646

Primary Outcome(s)

Plasma PK: t 1/2 [Time Frame: Baseline and Week 10]

Plasma PK: tmax [Time Frame: Baseline and Week 10]

Change from baseline in concentration of SM04646 in BAL fluid ("BAL" arm only) [Time Frame: Baseline and Week 2]

Plasma PK: accumulation ratio [Time Frame: Baseline and Week 10]

Safety and tolerability: number of subjects with a clinically significant change from baseline in oxygen saturation [Time Frame: Week 24]

Safety and tolerability: number of subjects with a clinically significant change from baseline in electrocardiogram (ECG) parameters [Time Frame: Week 24]

Safety and tolerability: treatment-emergent adverse events (TEAEs) [Time Frame: Week 24]

Plasma PK: AUC [Time Frame: Baseline and Week 10]

Safety and tolerability: number of subjects with a clinically significant change from baseline in vital signs [Time Frame: Week 24]

Plasma pharmacokinetics (PK): Cmax [Time Frame: Baseline and Week 10]

Safety and tolerability: number of subjects with a clinically significant change from baseline in clinical laboratory tests [Time Frame: Week 24]

Secondary Outcome(s)

Categorical analysis of FVC (% predicted) change [Time Frame: Baseline and Week 24]

Change from baseline of biomarker concentration isolated from serum [Time Frame: Baseline and Week 24]

Change from baseline of diffusion capacity of the lung for carbon monoxide (DLCO) (% predicted corrected for hemoglobin) [Time Frame: Baseline and Week 24]

Change from baseline of qualitative HRCT [Time Frame: Baseline and Week 24]

Change from baseline of forced expiratory volume in 1 second (FEV1) (% predicted) [Time Frame: Baseline and Week 24]

Change from baseline of FVC (liters) [Time Frame: Baseline and Week 24]

Change from baseline of FEV1 (liters) [Time Frame: Baseline and Week 24]

Change from baseline of quantitative high-resolution computed tomography (HRCT) (%) and mL) [Time Frame: Baseline and Week 24]

Change from baseline of forced vital capacity (FVC) (% predicted) [Time Frame: Baseline and Week 24]

Change from baseline of quantitative high-resolution computed tomography (HRCT) (mL) [Time Frame: Baseline and Week 24]

Time to disease progression [Time Frame: Week 24]

Secondary ID(s)

SM04646-IPF-03

Source(s) of Monetary Support

Please refer to primary and secondary sponsors