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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03591926




Registration number
NCT03591926
Ethics application status
Date submitted
9/07/2018
Date registered
19/07/2018
Date last updated
9/10/2018

Titles & IDs
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)
Secondary ID [1] 0 0
SM04646-IPF-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SM04646

Experimental: "BAL" Arm - Subjects in this arm will undergo a bronchoalveolar lavage (BAL) procedure at baseline and after two weeks of treatment.

Experimental: "Non-BAL" Arm - Subjects in this arm will not undergo any BAL procedures.


Treatment: Drugs: SM04646
Nebulized, inhaled solution; single dose concentration dosed once per day for 12 weeks; dosing pattern will follow a 2 weeks on, 2 weeks off regimen, wherein subjects will dose 5 consecutive days of each 7 day "on" week.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability: treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
Week 24
Primary outcome [2] 0 0
Safety and tolerability: number of subjects with a clinically significant change from baseline in clinical laboratory tests
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Safety and tolerability: number of subjects with a clinically significant change from baseline in vital signs
Timepoint [3] 0 0
Week 24
Primary outcome [4] 0 0
Safety and tolerability: number of subjects with a clinically significant change from baseline in oxygen saturation
Timepoint [4] 0 0
Week 24
Primary outcome [5] 0 0
Safety and tolerability: number of subjects with a clinically significant change from baseline in electrocardiogram (ECG) parameters
Timepoint [5] 0 0
Week 24
Primary outcome [6] 0 0
Plasma pharmacokinetics (PK): Cmax
Timepoint [6] 0 0
Baseline and Week 10
Primary outcome [7] 0 0
Plasma PK: tmax
Timepoint [7] 0 0
Baseline and Week 10
Primary outcome [8] 0 0
Plasma PK: AUC
Timepoint [8] 0 0
Baseline and Week 10
Primary outcome [9] 0 0
Plasma PK: t 1/2
Timepoint [9] 0 0
Baseline and Week 10
Primary outcome [10] 0 0
Plasma PK: accumulation ratio
Timepoint [10] 0 0
Baseline and Week 10
Primary outcome [11] 0 0
Change from baseline in concentration of SM04646 in BAL fluid ("BAL" arm only)
Timepoint [11] 0 0
Baseline and Week 2
Secondary outcome [1] 0 0
Change from baseline of forced vital capacity (FVC) (% predicted)
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [2] 0 0
Change from baseline of FVC (liters)
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Categorical analysis of FVC (% predicted) change
Timepoint [3] 0 0
Baseline and Week 24
Secondary outcome [4] 0 0
Time to disease progression
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Change from baseline of forced expiratory volume in 1 second (FEV1) (% predicted)
Timepoint [5] 0 0
Baseline and Week 24
Secondary outcome [6] 0 0
Change from baseline of FEV1 (liters)
Timepoint [6] 0 0
Baseline and Week 24
Secondary outcome [7] 0 0
Change from baseline of diffusion capacity of the lung for carbon monoxide (DLCO) (% predicted corrected for hemoglobin)
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
Change from baseline of quantitative high-resolution computed tomography (HRCT) (%) and mL)
Timepoint [8] 0 0
Baseline and Week 24
Secondary outcome [9] 0 0
Change from baseline of quantitative high-resolution computed tomography (HRCT) (mL)
Timepoint [9] 0 0
Baseline and Week 24
Secondary outcome [10] 0 0
Change from baseline of qualitative HRCT
Timepoint [10] 0 0
Baseline and Week 24
Secondary outcome [11] 0 0
Change from baseline of biomarker concentration isolated from serum
Timepoint [11] 0 0
Baseline and Week 24

Eligibility
Key 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
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 Investigator, within 30 days
prior to study start

10. Human immunodeficiency virus (HIV), hepatitis C, or active hepatitis B infection

11. Clinically significant hepatic impairment (e.g., Child-Pugh A or greater
severity)

12. Symptomatic coronary artery disease, congestive heart failure (CHF) New York
Heart Association (NYHA) Class II-IV, myocardial infarction (MI), or unstable
angina within 6 months prior to study start

13. Hypertension (systolic blood pressure (SBP) >160 millimeters of mercury (mmHg) or
diastolic blood pressure (DBP) >100 mmHg)

14. Hypotension (blood pressure (BP) less than 90/60 mmHg) or mean arterial blood
pressure (MAP) < 65 mmHg

15. Current use of supplemental oxygen therapy for any condition

- Subjects who are immediate family members (spouse, parent, child, or sibling;
biological or legally adopted) of personnel directly affiliated with the study at the
investigative site, or are directly affiliated with the study at the investigative
site

- Subjects employed by Samumed Pacific Pty Ltd, or any of its affiliates or development
partners (that is, an employee, temporary contract worker, or designee) responsible
for the conduct of the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/01/1900
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/1900
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Concord
Recruitment hospital [3] 0 0
Research Site - Bedford Park
Recruitment hospital [4] 0 0
Research Site - Clayton
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Bedford Park
Recruitment postcode(s) [4] 0 0
- Clayton
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
Country [2] 0 0
New Zealand
State/province [2] 0 0
Dunedin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biosplice Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
SM04646-IPF-03 is a Phase 2a, multi-center, open-label study evaluating the safety and
efficacy of a single inhaled, nebulized dose of SM04646 solution over a 12-week treatment
regimen in subjects with mild to moderate IPF. A total of approximately 24 subjects will be
enrolled in the study (approximately 12 subjects into the "non-bronchoalveolar lavage [BAL]"
arm and approximately 12 subjects into the "BAL" arm). Subjects that currently do not
require, have failed to tolerate, or have opted not to have treatment with pirfenidone or
nintedanib will have the option of participation in the "BAL" arm or participation in the
"non-BAL" arm. Subjects currently receiving treatment with pirfenidone or nintedanib must be
on stable treatment for a minimum of 12 weeks prior to the Screening Visit. Subjects
currently on treatment with pirfenidone or nintedanib may participate in the "non-BAL" arm
only.

Eligible subjects will participate in a treatment period of 12 weeks and a follow-up period
of 12 weeks. The treatment dosing pattern will follow a 2 weeks on, 2 weeks off regimen,
wherein subjects will dose 5 consecutive days of each 7 day "on" week.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03591926
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yusuf Yazici, M.D.
Address 0 0
Biosplice Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03591926