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A Study of NH280105 in Healthy Adult Participants

J

Jiangsu Nhwa Pharmaceutical

Status and phase

Not yet enrolling
Phase 1

Conditions

Alzheimer Disease

Treatments

Drug: Placebo
Drug: NH280105- SAD
Drug: NH280105- MAD

Study type

Interventional

Funder types

Industry

Identifiers

NCT06870058
NH280105-101

Details and patient eligibility

About

This is a Phase 1, randomized, double-blinded, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NH280105 in healthy volunteers. In addition, this study will evaluate the effects of food on NH280105 under a two-period study setting.

Full description

This study will be conducted in 2 parts: Part 1 (SAD) and Part 2 (MAD). Approximately 48 participants will be enrolled.

  • Part 1 (Cohorts 1, 2, and 4): The study design includes a double-blind, placebo-controlled setting for SAD cohorts.
  • Part 1 (Cohort 3): This cohort will be a double-blind, placebo-controlled, two-conditions (ie, fed vs. fasted), two-period, crossover setting for the Food-effect Cohort.
  • Part 2: The study design includes a double-blind, placebo-controlled setting for MAD cohorts.

Oversight will be provided by a Safety Review Committee (SRC). Safety, tolerability, and PK/PD data (if available) of the preceding dose levels in both Part 1 (SAD) and Part 2 (MAD) will be reviewed by the SRC for dose escalation and the actual doses to be administered may be adjusted accordingly.

Enrollment

48 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. Aged ≥ 18 years at the time of informed consent.

  2. At the discretion of the PI or designee, in good general health, with no significant medical history, and have no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP.

  3. Body mass index (BMI) between ≥ 18.0 and ≤ 32.0 kg/m2 and weight ≥ 50 kg.

  4. Clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee.

  5. Not pregnant or breastfeeding, or willing to cease breastfeeding.

  6. Woman of childbearing potential or fertile man agrees to use an acceptable method of contraception from the start of Screening until 90 days after the last dose of IP. Acceptable methods of contraception are defined in protocol.

    Notes:

    1. Males must be surgically sterile (> 30 days since vasectomy with no viable sperm) or, if engaged in sexual relations with a WOCBP, must agree to use an acceptable contraceptive method.
    2. Females or males with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle.
    3. Males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP.
  7. Able and willing to attend the necessary visits to the study site.

  8. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

Exclusion criteria

  1. Use of tobacco or nicotine products exceeding 5 cigarettes (or equivalent) per week in any form within 30 days prior to IP administration on Day 1, or unwillingness to refrain from smoking, vaping, or using any nicotine products for at least 48 hours before the first IP administration, the onfinement period, and any Follow-up Visits.

  2. Underlying physical or psychological medical condition that, in the opinion of the PI or designee, would make the participant unlikely to comply with the protocol or complete the study per protocol.

  3. Blood or plasma donation or had significant blood loss (400 mL) within 30 days prior to the first administration of IP.

  4. Fever (body temperature > 37.5°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening.

  5. Infections requiring parenteral antibiotics within 6 months prior to Screening.

  6. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibody.

  7. Positive pregnancy test at Screening and/or on Day -1.

  8. History of life-threatening infection (eg, meningitis).

  9. Receiving live vaccine within 30 days prior to IP administration on Day 1 or require receiving live vaccination during the study or within 30 days end of the study.

  10. Poor pill swallowing ability / poor venous access.

  11. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents; exceptions might be granted on a case-by-case basis upon agreement of the PI and the Sponsor.

  12. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening.

  13. Abnormal cardiac conditions and/or ECG findings at Screening

    • The Fridericia algorithm corrected QT interval (QTcF) of ECG during Screening Period is > 450 msec for males and > 470 msec for females or is considered abnormal with clinical significance as determined by the PI or designee.
    • Sustained (ie, 3 independent measurements within 30 minutes) heart rate (HR) > 100 or < 45 bpm.
    • Personal and/or family history of congenital long QT syndrome or sudden cardiac death.
  14. BP is greater than 140/90 mmHg or below 90/40 mmHg and are considered by the PI/designee to be clinically significant.

  15. History immunological disorders, auto-immune disorders, acquired or congenital immune deficiency, including autoimmune rheumatic disease.

    Note: participants with mild asthma controlled with occasional rescue inhaler only (no chronic therapy; no inhaled corticosteroids), and mild atopic dermatitis controlled with topic emollients only (no topical corticosteroids) are not excluded.

  16. Exposure to any drugs that cause significant immunosuppression (including experimental therapies as part of a clinical study) within 4 months or 5 elimination half-lives (whichever is longer), prior to Screening.

  17. Clinically significant abnormalities in laboratory test, including, including alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) at Screening. Repeat testing at Screening is acceptable for out-of-range values following approval by the PI/designee.

  18. Positive toxicology screening panel (urine test including qualitative identification of methamphetamine, opiates, cocaine, tetrahydrocannabinol (THC), pphencyclidine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants (TCAs), amphetamine), nicotine, and/or alcohol breath test at Screening or Day -1.

  19. History of substance abuse or dependency or history of recreational IV drug use over the last 12 months (by self-declaration).

  20. Regular alcohol consumption defined as > 10 standard drinks per week (where 1 standard drink = 360 mL of beer, 45 mL of 40% spirit or a 150 mL glass of wine) or > 4 standard drinks on any single day.

  21. Unwilling to refrain from alcohol, methylxanthines, poppy seeds, and caffeine and caffeine consumption starting 48 hours before admission to the study site, throughout the confinement period, and for 48 hours prior to sequential dosing and any Follow-up Visits.

  22. Use of any investigational medical device or investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first administration of the IP.

  23. Use of (or anticipated use of) any prescription drugs (other than hormonal contraception; oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring, or an intrauterine device [IUD]) within 30 days, OTC medication, nonsteroidal anti-inflammatory drug (NSAID), herbal remedies, supplements or vitamins within 14 days or 5 elimination half-lives (whichever is longer) prior to the first administration of IP and during the course of the study without prior approval of the PI and Sponsor MM. Simple analgesia (paracetamol) or other agents may be permitted at the discretion of the PI. Exception: Women of childbearing potential (WOCBP) are permitted to use hormonal contraception.

  24. Unwilling to refrain from strenuous exercise (including weightlifting) from 48 hours prior to admission to the study site and from 48 hours prior to any Follow-up Visits.

  25. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

  26. Anything that the PI considers would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.

  27. Consumption of any known liver enzyme inducers or inhibitors, including foods or beverages such as citrus fruits (eg, tangerines, grapefruits, sweet oranges, limes, kumquats, citrons, oranges, lemons, etc.) and their juices, is prohibited within 7 days prior to the first administration of the IP.

  28. Any major surgery within 6 months before Screening, or plan to have a surgery during the study. Participants meeting the following criterion are excluded from Part 1 - Cohort 3 (Food-effect Cohort).

  29. Inability or unwillingness to consume a standard high-fat meal, as described in FDA Guidance for fed vs. fasted PK studies.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

48 participants in 2 patient groups

NH280105-SAD
Experimental group
Description:
SAD: Participants will either receive NH280105 or placebo across 4 cohorts * Cohorts 1, 2 and 4: Single dose on Day 1. * Cohort 3: Single dose on Days 1 and 9.
Treatment:
Drug: NH280105- SAD
Drug: Placebo
NH280105- MAD
Experimental group
Description:
MAD: Participants will receive either NH280105 or placebo, once daily for 14 days across 2-3 cohorts.
Treatment:
Drug: NH280105- MAD
Drug: Placebo

Trial contacts and locations

1

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Central trial contact

Yujiao Fu

Data sourced from clinicaltrials.gov

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