This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows: - To assess the safety and tolerability of AHCQ administered as a single dose by oral inhalation in healthy individuals at escalating doses until either the maximum tolerated dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered. - To determine the recommended Phase 2a dose (RP2D). Secondary objectives: • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.
Study Design:
This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation
study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy
participants.
Escalating single doses of AHCQ will be studied in healthy participants. The study drug will
be administered by inhalation through the mouth, and participants will be encouraged to
exhale through the nose. The study drug, AHCQ, will be administered starting at an initial
dose of 20 mg (Cohort A1, 1 mL of 20 mg/mL AHCQ solution) with a proposed subsequent doses of
50 mg (Cohort A2, 1 mL of 50 mg/mL AHCQ).
Number of Participants (Planned):
Two dose levels are planned to be evaluated. Each cohort will comprise 8 participants (6
active, 2 placebo). Therefore, 16 participants will initially be planned to be enrolled in
the study. Additional participants may be enrolled if one or more enrolled participants do
not complete the study.
Drug: Aerolized Hydroxychloroquine Sulfate
sterile AHCQ 100 mg/mL for inhalation, is a clear solution packaged in clear glass vials and stored at room temperature.
Other Name: AHCQ
Other: Placebo
The placebo product and diluent solution is sodium chloride inhalation solution, United States Pharmacopeia (USP) 0.9%.
Inclusion Criteria:
1. Willing and able to give written informed consent.
2. Males or females aged ≥18 years old.
3. Good general health as determined by no acute illness and no clinically significant
abnormal findings on medical history, vital signs, laboratory tests, or physical
examination at screening that, in the opinion of the PI, would interfere with study
drug administration, jeopardize the safety of the study participant, or impact the
validity of the study results; participants with stable chronic illness are allowed at
the discretion of the PI.
4. An interpretable 12-lead ECG with a corrected QT (QTc) interval ≤450 ms, according to
Bazett's formula, without evidence of clinically significant abnormal findings.
5. Normal FEV1/FVC ratio, defined as any value above 0.7 or above the lower 5th
percentile of normal AND FEV1 >80% of predicted or above the lower 5th percentile of
normal.
6. Pulse oximetry 02 saturation ≥95% in room air.
7. Negative test result for COVID-19 within 7 days of Day 1 AND concurrent with local
hospital policy:
- A nasopharyngeal swab tested with the ID NOW COVID-19 assay (Abbot). OR
- A negative RNA-based test result of an oropharyngeal or nasopharyngeal swab or
saliva sample performed according to CLIA/CLEP.
8. Females of child-bearing potential must be non-pregnant, non-lactating, have a
negative urine pregnancy test at screening, and agree to use an acceptable form of
birth control for 200 days after the last administration of the study drug. Females
are considered of non-childbearing potential if they are postmenopausal (last
menstrual period at least 1 year before screening) or have been surgically sterilized
(documented hysterectomy, tubal ligation, or bilateral oophorectomy) for at least 6
months at screening.
9. Willing to comply with protocol-defined procedures and complete all study visits.
10. Willing to use the Inhalation System and exhale through the nose.
11. Adequate venous access in the left or right arm to allow collection of required blood
samples.
12. Participant understands and communicates in English.
13. Serum Potassium level ≥3.5 mEq/L, Serum Magnesium level ≥1.5 mg/dL, and Serum Calcium
≥8.5 mg/dL.
Exclusion Criteria:
1. Any self-reported symptoms of influenza-like or COVID-19-like illness in the 14 days
preceding the study visit: Fever >101.4 °F, sore throat, nasal congestion, post-nasal
discharge, shortness of breath, gastrointestinal distress, wheezing, cough, headache,
or fatigue.
2. Any history of diagnosed chronic lung disease, including but not limited to asthma or
chronic obstructive lung disease.
3. Symptoms of seasonal allergies or use of any drugs for seasonal allergies or any
inhaled (oral/nasal) drugs in the 2 weeks prior to Day 1. Mild seasonal allergy
symptoms that have not altered sleep or activity patterns nor required use of
over-the-counter (OTC) or prescription medications are allowed.
4. Any close contact exposure in the past 28 days to a person who was diagnosed as having
COVID-19, with or without laboratory confirmation, during that close contact exposure
or in the ensuing 14 days OR a similar encounter with a person who was determined to
have suspected COVID-19, defined by that person being ordered to enter isolation for
that indication by a medical authority. Close contact is defined as being within
approximately 6 feet of a COVID-19 case for a prolonged (>10 minutes) period of time
and can occur while caring for, living with, visiting, or sharing a healthcare waiting
area or room with a COVID-19 patient OR having direct contact with infectious
secretions of a COVID-19 patient (e.g., being coughed on), if such contact occurred
while not wearing the recommended personal protective equipment for that type of
contact [e.g., gowns, gloves, N95 respirator (or equivalent), eye protection].
5. Any participant with a history of SARS-CoV-2 infection that was confirmed by testing
or diagnosed without testing within 4 weeks preceding Day 1. If infection occurred
more than 4 weeks prior, candidates may be enrolled if they meet the rest of the
eligibility criteria.
6. Any participant with a history severe respiratory illness that required
hospitalization in the 60 days preceding Day 1 OR any participant with a history
severe respiratory illness that required hospitalization in the preceding 120 days
without full recovery.
7. Participation in another clinical study that involved treatment with an
investigational product or device within 30 days of screening or during the study.
8. Participants with a known history of human immunodeficiency virus (HIV) infection.
9. Known, active hepatitis A, B, or C infection.
10. History of bronchospasm in response to use of an inhalation device.
11. Use of any prescription medication (except oral contraceptives) during the 30 days
prior to study dosing that may affect drug absorption, metabolism and excretion,
prolong the QTc interval, affect drug efficacy, or increase the risk of adverse
reactions, unless approved by the Principal Investigator.
12. Use of any OTC product, herbal product, diet aid, hormone supplement, etc., within 7
days prior to dosing unless approved by the Principal Investigator.
13. Unwilling or unable to provide written informed consent.
14. Any known hypersensitivity to quinolines (e.g., hydroxychloroquine, chloroquine,
primaquine, quinine) or known history of glucose-6-phosphate dehydrogenase (G6PD)
deficiency or any contraindication to oral hydroxychloroquine.
15. Known retinopathy, fundus disease, or macular disease.
16. Diagnosis of long QT Syndrome.
17. Smoking of tobacco or non-tobacco substances, or vaping, within the last 6 months.
18. Severe obesity (body mass index [BMI] ≥35 kg/m2).
The Rockefeller University
New York, New York, United States
Ohad S Bentur, MD, MHA, Principal Investigator
Rockefeller University