Intranasal CHF6467 safety and absorption in healthy adults

A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of CHF6467 After Single and Repeated Ascending Doses by Intranasal Route in Healthy Adult Subjects

This will test single and repeated nasal doses of CHF6467 in healthy adults to see if they are safe and how the drug gets into the blood and the fluid around the brain.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 68 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Chiesi Farmaceutici S.p.A. (industry)
• Locations: 1 site (Sofia)
• Trial ID: NCT07163182 on ClinicalTrials.gov

What this trial studies

This Phase 1, placebo-controlled study enrolls 68 healthy adults to characterize safety, tolerability, pharmacokinetics and immunogenicity after intranasal dosing of CHF6467. The trial is split into Part 1 (single ascending doses over a 4-day period) and Part 2 (multiple ascending doses over an 11-day period), with screening, treatment and follow-up visits for each part. Blood and cerebrospinal fluid samples will be collected to measure how the drug is absorbed, distributed, metabolized and cleared, and samples will be tested for anti-drug antibodies. Safety monitoring includes clinical exams, vital signs and adverse event reporting throughout the treatment and follow-up periods.

Who should consider this trial

Good fit: Healthy men and women aged 18–55 with BMI 18.0–30.0, weight 50–85 kg, non-smokers or light ex-smokers, and otherwise in good health are eligible to participate.

Not a fit: People with active medical conditions seeking therapeutic benefit, those outside the age/BMI/weight ranges, current heavy smokers, or anyone unable to travel to the study site are unlikely to receive direct benefit from participation.

Why it matters

Potential benefit: If successful, this work could support a nasal delivery option that reaches the central nervous system and enable future treatments for brain-related conditions.

How similar studies have performed: Intranasal dosing and single/multiple ascending dose studies are established methods and some intranasal drugs have shown CNS delivery, but CHF6467's specific formulation and CNS exposure profile are being tested for the first time here.

Eligibility criteria

Inclusion Criteria:

1. Subject's written informed consent obtained prior to any study-related procedures;
2. Willingness and ability to understand the risks involved and to understand and comply with the study procedures;
3. Healthy male and female subjects, aged 18-55 years inclusive at screening;
4. Weight ≥ 50 kg and \<85 kg and Body Mass Index (BMI) between 18.0 and 30.0 kg/m² inclusive at screening and on Day -1;
5. Non-smoker or ex-smoker who smoked less than 5 pack years (Pack years = the number of cigarette packs per day times the number of years) and stopped smoking at least 1 year prior to screening;
6. Good physical condition and mental status determined by the Investigator, based on the subject's medical history and general clinical examination at screening and Day -1;
7. Vital signs within normal limits at screening and at Day-1: 60 mmHg ≤ diastolic blood pressure (DBP) ≤ 89 mmHg, 90 mmHg ≤ systolic blood pressure (SBP) ≤ 139 mmHg (three measures performed after at least 5 minutes of resting; the mean value must be within the defined range). Axillary body temperature of 35.5-37.0º Celsius inclusive;
8. Bedside 12-lead electrocardiogram (ECG) considered as normal (45 bpm ≤ heart rate \[HR\] ≤ 100 bpm, 120 ms ≤ PR interval \[PR\] ≤ 210 ms, QRS interval \[QRS\] ≤ 120 ms, QT interval \[QT\] corrected using Fridericia's formula \[QTcF\] ≤ 450 ms for males and ≤ 470 ms for females) at screening visit and Day -1; the mean value of three measurements must be within the range.
9. Males fulfilling one of the following criteria:

   1. Males with pregnant or non-pregnant women of childbearing potential (WOCBP) partners: they must be willing to use male condom from the signature of the informed consent and until the follow-up visit or
   2. Non-fertile male subjects (contraception is not required in this case) or
   3. Males with partner not of childbearing potential (contraception is not required in this case);
10. Female subjects fulfilling one of the following criteria:

    1. Women of non-childbearing potential (WOCBP) defined as physiologically incapable of becoming pregnant (i.e., post-menopausal or permanently sterile). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per Investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone (FSH) levels (according to local laboratory ranges);
    2. WOCBP fulfilling one of the following criteria:

    i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method preferably with low user dependency from the signature of the informed consent and until the follow-up visit; or ii. WOCBP with non-fertile male partners (contraception is not required in this case).

Exclusion Criteria:

1. The subject has taken non-permitted concomitant medications in the predefined period prior to screening or prior to randomisation or is expected to take non-permitted concomitant medications during the study;
2. Participation to investigational study: subjects who have received any investigational drug within the 30 days (60 days for biologics) or a more appropriate time as determined by the Investigator (e.g. approximately 5 half-lives of the investigational drug whatever is longer);
3. Significant nasal congestion or signs of nasal damage, bleeding, excoriation or ulceration at physical examination at screening or Day -1;
4. History of frequent nosebleeds;
5. Any ongoing acute (e.g. non-allergic rhinitis) or chronic (e.g. chronic rhinosinusitis or chronic purulent postnasal drip) condition of the nasal cavity, or clinically significant physical finding (e.g. nasal polyps, nasal structural abnormalities, nasal trauma, severe nasal septal deviation) which, in the opinion of the Investigator, can interfere with the administration or absorption of the study medication. Subjects with recent upper respiratory tract infections will be allowed in the study only if their nasal symptoms have been completely resolved for more than 2 weeks prior to screening;
6. Clinically significant abnormal 24-hour Holter at screening;
7. Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic or psychiatric disorder that may interfere with successful completion of this protocol, any known malignancies, or any condition that in Investigator's opinion may pose the subject at risk from participating in the study;
8. Any clinically relevant abnormal laboratory value at screening or Day -1suggesting an undiagnosed condition that requires further clinical investigation or may impact the safety of the subject or the evaluation of the study results according to the Investigator's judgement; Note: In case of abnormal laboratory values that could indicate a temporary condition, the test can be repeated once before randomisation;
9. For females only: pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until termination of the gestation, confirmed by a positive serum human chorionic gonadotropin laboratory test. Serum pregnancy test to be performed at screening and urine pregnancy test to be performed at Day -1.

Where this trial is running

Sofia

• Bulgaria MC Comac Medical Ltd. — Sofia, Bulgaria (RECRUITING)

Study contacts

• Principal investigator: Maya Dabcheva, MD — MC Comac Medical Ltd.
• Study coordinator: Chiesi Clinical Trial Info

Conditions: Healthy Volunteers, Single Ascending Dose, Multiple Ascending Dose, Intranasal, Cerebrospinal fluid