SAD and MAD of Inhaled AR-501 in Health Adults and P. Aeruginosa Infected Cystic Fibrosis Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 20 March 2023
• Main ID: NCT03669614
• Date of registration: 30/08/2018
• Prospective Registration: Yes
• Primary sponsor: Aridis Pharmaceuticals, Inc.
• Public title: SAD and MAD of Inhaled AR-501 in Health Adults and P. Aeruginosa Infected Cystic Fibrosis Subjects
• Scientific title: A Phase 1/2a Randomized, Double-Blind, Two-Part, Dose-Ascending, Multicenter Study of the Safety and PK of AR-501 (Gallium Citrate), Administered Via Inhalation, in Healthy Adult and P. Aeruginosa Infected Cystic Fibrosis Subjects
• Date of first enrolment: December 7, 2018
• Target sample size: 102
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03669614
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Lynne M Deans, MT

• Name: Alan H Cohen, MD
• Affiliation: Aridis Pharmaceuticals, Inc.

• Name: Hasan S Jafri, MD, FAAP
• Affiliation: Aridis Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria (HV Subjects):

1. Written informed consent given by the subject.

2. At least = 18 years old and < 50 years of age.

3. Healthy with no acute medical condition for = 2 weeks prior to screening and no known
chronic medical condition requiring regular medical follow up and care.

4. Body mass index (BMI) between 18 and 30 kg/m2, inclusive.

5. Currently nonsmoking and no history of using nicotine/tobacco-containing products for
= 5 years prior to screening.

6. Normal chest X-ray, per opinion of the Investigator.

7. FEV1 = 80% of predicted values.

8. No history or current illicit, pharmaceutical drug or alcohol abuse within = 5 years
prior to screening.

9. A female subject must meet one of the following criteria:

If of childbearing potential - agrees to use one of the accepted contraceptive
regimens from at least 30 days prior to the first administration of the study
medication, during the study, and for at least 90 days after the last dose of the
study medication. An acceptable method of contraception includes one of the following:

- Abstinence from heterosexual intercourse

- Hormonal contraceptives (birth control pills, injectable/implant/insertable
hormonal birth control products, transdermal patch)

- Intrauterine device (with or without hormones), OR

- Agrees to use a double barrier method (e.g., condom and spermicide) during the
study and for at least 90 days after the last dose of the study medication

If a female of non-childbearing potential, the subject should be surgically sterile
(i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation)
or in a menopausal state (at least 1 year without menses), as confirmed by follicle
stimulating hormone (FSH) levels.

10. A male subject must agree to use a double barrier method (e.g., condom and spermicide)
during the study and for at least 90 days after the last dose of the study medication.

Inclusion Criteria (CF Subjects):

1. Written informed consent given by the subject.

2. At least18 years old

3. Documentation of a CF diagnosis as evidenced by one or more clinical features
consistent with the CF phenotype and one or more of the following criteria:

- Sweat chloride equal to or greater than 60 mmol/liter by quantitative pilocarpine
iontophoresis test (QPIT)

- Two well-characterized, disease-causing mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene.

4. Confirmation of current colonization/infection with P. aeruginosa defined as: a
positive sputum or oropharyngeal swab culture at screening.

5. Respiratory symptoms and CF status are stable with no acute exacerbation at the time
of randomization.

6. BMI = 18 kg/m2

7. Currently non-smoking and no history of using nicotine/tobacco-containing products or
smoking/vaping (inhaled tobacco products or other inhaled substances) for = 1 year
prior to screening.

8. FEV1 = 45% of predicted values.

9. Serum creatinine and total bilirubin are both < 1.5 x upper limit of normal (ULN)
range (isolated bilirubin > 1.5 x ULN range is acceptable if bilirubin is fractionated
and direct bilirubin is < 35%).

10. A female subject must meet one of the following criteria:

- If of childbearing potential - agrees to use one of the accepted contraceptive
regimens from at least 21 days prior to the first administration of the study
medication, during the study, and for at least 28 days after the last dose of the
study medication. An acceptable method of contraception includes one of the
following:

- Abstinence from heterosexual intercourse

- Hormonal contraceptives (birth control pills, injectable/implant/insertable
hormonal birth control products, transdermal patch)

- Intrauterine device (with or without hormones), OR

- Agrees to use a double barrier method (e.g., condom and spermicide) during
the study and for at least 28 days after the last dose of the study
medication

- If a female of non-childbearing potential, the subject should be surgically
sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or
tubal ligation) or in a menopausal state (at least 1 year without menses), as
confirmed by FSH levels.

11. A male subject must agree to use a double barrier method (e.g., condom and spermicide)
during the study and for at least 28 days after the last dose of the study medication.

12. Ability to produce an oropharyngeal sample (e.g., Expectorated Sputum or throat swab).

Exclusion Criteria (HV Subjects):

None of the following criteria can be met.

1. Female subjects who are currently pregnant or lactating.

2. Oral temperature above 37.5ºC at the time of screening or prior to randomization.

3. Clinically abnormal renal function, evidenced by serum creatinine > 1.5 mg/dL.

4. Need for using any nephrotoxic agents during the study.

5. Known allergy or hypersensitivity to albuterol.

6. Significantly abnormal liver function:

1. Total bilirubin >1.5 x upper limit of the normal range (ULN),

2. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 x ULN
and alkaline phosphatase (ALP) > 2 x ULN

7. Hemoglobin <10 g/dL

8. Abnormal corrected serum calcium concentration prior to enrollment.

9. History or current use of illicit, pharmaceutical drug or alcohol abuse within 5 years
prior to screening.

10. Positive urine screen for alcohol, cotinine and/or drugs of abuse at screening and
admission.

11. Positive test results for Human Immunodeficiency Virus (HIV)-1/HIV-2 antibodies,
Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb).

12. Inability to comply with any study requirements based on judgement of the
Investigator.

13. Any medical, psychological, cognitive, social or legal conditions that would interfere
in the ability to give an informed consent and/or participate fully in the study.

14. Participation in another clinical trial involving receipt of an investigative product
within 30 days before screening.

15. Any other reason as determined by an Investigator.

Exclusion Criteria (CF Subjects):

None of the following criteria can be met.



Age minimum: 18 Years
Age maximum: 49 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Inhaled Placebo

Drug: Inhaled AR-501

Primary Outcome(s)

Clinical safety profile (adverse events) - Multiple Ascending Dose [Time Frame: up to 28 days after last dose administration]

Clinical safety profile (adverse events) - Single Ascending Dose [Time Frame: 28 days following dose administration]

Secondary Outcome(s)

Pharmacokinetics (PK) Profile - MAD ?z [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - MAD t½ [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - SAD Cmax [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - MAD AUC0-inf [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - SAD AUC0-last [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - SAD Tmax [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - MAD AUC0-last [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - MAD Clp [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - MAD Cmax [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - SAD Clp [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - MAD Tmax [Time Frame: up to 28 days after last dose administration]

Pharmacokinetics (PK) Profile - SAD AUC0-inf [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - SAD ?z [Time Frame: 28 days following dose administration]

Pharmacokinetics (PK) Profile - SAD t½ [Time Frame: 28 days following dose administration]

Secondary ID(s)

AR-501-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors