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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03669614
Recruitment Status : Active, not recruiting
First Posted : September 13, 2018
Last Update Posted : June 22, 2020
Sponsor:
Information provided by (Responsible Party):
Aridis Pharmaceuticals, Inc.

Brief Summary:
A Phase 1/2a randomized, double-blind, two-part, dose-ascending, multicenter study of the safety and pharmacokinetics of AR-501 (gallium citrate), administered via inhalation, in healthy adult and P. aeruginosa infected cystic fibrosis subjects.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: inhaled AR-501 Drug: inhaled AR-501 placebo Phase 1 Phase 2

Detailed Description:

Three dose levels will be assessed in succession, first in HV subjects, then in CF subjects. The study will be performed in 4 stages, beginning with the HV cohort single-ascending-dose (SAD) phase, followed by the HV cohort multiple-ascending-dose (MAD) phase, and then the CF cohort SAD phase, and finally the CF cohort MAD phase.

The HV cohort will include up to 48 subjects. The CF cohort will have the same composition of subjects. Thus, the total number of subjects is 96.

The study will be performed at a Phase 1/2 Clinical Study Unit for the HV cohort and at 9 to 12 Cystic Fibrosis Foundation (CFF)-accredited Therapeutic Development Network (TDN) clinical trial sites located in the United States for the CF cohort.

Subjects who meet all eligibility criteria, including giving informed consent, will be enrolled and undergo a screening period of 28 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

SAD Phase The HV cohort will include up to 24 adult subjects in 3 groups (8 per dose group). In each dose group, subjects will be randomly assigned in a 3:1 ratio to the active drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving placebo in a double-blind manner.

The MAD phase of the study will include up to an additional 24 adult subjects in 3 dose groups (also 8 per dose group). In each dose group, subjects will be randomly assigned in a 3:1 ratio to active study drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving placebo in a double-blind manner.

Cystic Fibrosis Cohort The CF cohort, consisting of 24 adult CF subjects, will undergo the same treatment and monitoring process as the HV cohort during the SAD phase, including the use of sentinel subjects in the first dose group.

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A P1/2a 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
Actual Study Start Date : December 7, 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Active Comparator: AR-501 inhaled
low , medium, high dose of inhaled AR-501
Drug: inhaled AR-501
single and multiple ascending doses of inhaled AR-501
Other Name: inhaled Gallium Citrate

Placebo Comparator: inhaled AR-501 Placebo
low, medium, high dose of inhaled placebo
Drug: inhaled AR-501 placebo
single and multiple ascending doses of inhaled placebo




Primary Outcome Measures :
  1. Respiratory tolerability - Single Ascending Dose [ Time Frame: up to 14 days after drug administration ]
    Spirometry

  2. Respiratory tolerability - Multiple Ascending Dose [ Time Frame: up to 8 weeks after last dose administration ]
    Spirometry


Secondary Outcome Measures :
  1. Cmax - Observed maximum serum concentration [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics

  2. Tmax - Time to reach maximum serum concentration [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics

  3. AUC0 - last area under the concentration time curve [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics

  4. AUC0-∞ Area under the concentration time curve from zero to infinite time [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics

  5. Terminal phase elimination rate [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics

  6. Terminal elimination half-life [ Time Frame: 28 days following dose administration ]
    Pharmacokinetics Characteristics


Other Outcome Measures:
  1. Investigate lung function in chronically P. aeruginosa-infected adult CF subjects [ Time Frame: Up to 28 days after drug administration ]
    Spirometry

  2. Investigate effect of AR-501 on sputum bacteriology in chronically P. aeruginosa-infected adult CF subjects [ Time Frame: 28 days after drug administration ]
    Bacterial culture



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (Healthy volunteer phase):

  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.

  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.

Exclusion Criteria (healthy volunteer phase):

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03669614


Locations
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United States, Kansas
Altasciences/Vince and Associates Clinical Research
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Aridis Pharmaceuticals, Inc.
Investigators
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Study Director: Lynne M Deans Aridis Pharmaceuticals, Inc.
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Responsible Party: Aridis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03669614    
Other Study ID Numbers: AR-501-001
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: June 22, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Gallium citrate
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals