Clinical trial NCT06981299: A Phase 1 Study of PROT-001.
Official title: A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo-Controlled 3-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PROT-001 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Protego Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-20
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo-Controlled 3 Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of PROT-001, and the Effect of Food and Age on the Pharmacokinetics of PROT-001 in Healthy Adult Participants

Detailed description: This study will enrol approximately 102 participants, in three parts:

Part 1 is a single ascending (increasing) dose (SAD) study, where approximately 56 participants will receive a single dose of the study drug or placebo.

Part 2 is a multiple ascending (increasing) dose (MAD) study, where approximately 24 participants will receive multiple doses of the study drug or placebo for up to 14 days.

Part 3 is a food effect (FE) and age effect (AE) study, where approximately 12 participants in the food effect part of the study will receive 2 doses of the study drug: 1 dose after avoiding food for a set amount of time (fasted state), and 1 dose immediately after consuming a meal (fed state). Approximately 10 participants in the age effect part of the study will receive a single dose of the study drug after avoiding food for a set amount of time (fasted state).

Eligibility criteria: Inclusion Criteria:

1. Capable of providing written, signed, and dated participant informed consent prior to any study-related procedures, as described in Section 10.1.4.
2. For all study parts except Part 3 (Age-Effect study), participants must be between 18 and 65 years of age (inclusive) at the time of Screening (signing the ICF). For Part 3 (Age-Effect study) only, participants must be \>65 to 75 years of age at the time of Screening.
3. Has a body mass index (BMI) of 18 to 32 kg/m2 (inclusive) and a body weight of ≥50 kg.
4. Is judged by the Investigator to be generally healthy, as determined by a medical history without major pathology, and no clinically significant findings based on physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory results obtained at Screening and on days of admission to the study site (Day -1 and Day 14, as appropriate).
5. For all study parts except Part 3 (Age-Effect study), estimated glomerular filtration rate (eGFR) must be \>90 mL/min/1.73 m2 at Screening; for Part 3 (Age-Effect study), eGFR must be ≥60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation \[2021\]).
6. Has a resting (at least 5 minutes) pulse of 40 to 100 beats per minute and systolic and diastolic blood pressure (BP) of 90-140/40-90 mmHg.
7. Participants assigned female at birth are eligible to participate if they are not pregnant, not breastfeeding, and at least ONE of the following conditions applies:

   * Are a participant of nonchildbearing potential:
   * Surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or
   * Are postmenopausal (amenorrhea for ≥12 months without an alternative medical cause AND a follicle-stimulating hormone \[FSH\] level \>40 IU/L), or
   * Is a woman of childbearing potential (WOCBP) and agree to have their partner use a condom, and, if their partner is not vasectomized (with documented azoospermia), to use a highly effective method of contraception consistently and correctly starting from 1 month prior to Screening until at least 45 days after the last dose of IP.
8. Participants assigned male at birth who are sexually active with a female partner of childbearing potential are eligible to participate if they agree to use a condom, and have either been vasectomized (with documented azoospermia) or agree to have their partner use a highly effective method of contraception from Day 1 until at least 105 days after the last dose of IP.
9. Participants must refrain from donating eggs (ova, oocytes) from Day 1 until at least 45 days or sperm from Day 1 until at least 105 days after receiving the last dose of the IP.
10. Participants, who, in the opinion of the Investigator, can and will comply with the requirements and restrictions, including lifestyle restrictions listed in the Protocol.
11. Able to swallow an oral solid-dosage form of medication.
12. For Part 3 (Food-Effect study) only, able to consume a standardized high-fat meal.

Exclusion Criteria:

1. History or current evidence of a clinically significant or uncontrolled underlying condition, including but not limited to cardiovascular, hepatic, renal, hematological, infectious, autoimmune, neurological, psychiatric, endocrine, gastrointestinal, reproductive, pulmonary, or ocular. Clinically significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation or which could affect the endpoint analysis if the disease/condition worsened during the study. EXCEPTION: Fully resolved childhood asthma is not exclusionary.
2. History of or current invasive malignancy including hematological malignancies. Participants with a history of basal cell or squamous cell carcinoma or other carcinomas in situ that has been treated with no evidence of recurrence within 1 year prior to Screening will be allowed for inclusion, as judged by the Investigator.
3. History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
4. Any current active infections, including localized infections, or any recent history of active infections, cough, or fever within 1 week prior to IP administration (including severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\]), or any history of recurrent or chronic infections.
5. Known history of significant multiple and/or severe allergies (e.g., food, drug, or latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or nonprescription drugs or food. EXCEPTION: Untreated, asymptomatic, seasonal allergies are not exclusionary.
6. Family history of sudden death or of congenital prolongation of the QT interval corrected for heart rate (QTc) or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
7. Known or suspected hypersensitivity to any component of the finished dosage form of PROT-001.
8. Tested positive for hepatitis B surface antigen, anti-hepatitis C virus antibodies, and anti-human immunodeficiency virus 1 and 2 antibodies at Screening.
9. In the 12-lead ECG assessment at Screening or on days of admission to the study site (Day -1 and Day 14, as appropriate), QTcF \>450 msec. NOTE: One repeat screen is allowed at the discretion of the Investigator.
10. Has absolute neutrophil count (ANC) \<2 × 109/L or aspartate transaminase (AST) and alanine transaminase (ALT) \>1.5 × ULN, or INR \>1.2 at Screening or on days of admission to the study site (Day -1 and Day 14, as appropriate).
11. Has positive urine drug (excluding positive for cotinine) or alcohol breath test results at Screening or on days of admission to the study site (Day -1 and Day 14, as appropriate).
12. Use of more than 10 tobacco nicotine-containing products (e.g., 10 cigarettes) per week within 3 months prior to the first IP administration and should agree to follow the restrictions related to tobacco/nicotine-containing consumption during the study, as outlined in the Protocol.
13. Any history of alcohol abuse, with an average intake exceeding 21 drinks per week for men, 14 drinks per week for women, or \>4 drinks in 1 sitting several times a week (1 drink is equivalent to 12 g alcohol \[i.e., 150 mL of wine, 360 mL of beer, or 45 mL of 80-proof distilled spirits\]) or drug addiction (including soft drugs like cannabis products).
14. Use of any prescription or nonprescription medications, including over-the-counter (OTC) medications, vitamins, multivitamins, recreational drugs, dietary supplements, and herbal remedies such as St. John's Wort extract, or drugs considered likely to interfere with the safe conduct of the study within 7 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of the IP, or their planned use during the study period. EXCEPTIONS: After randomization, ibuprofen (≤1.2 g in 24 hours) and/or paracetamol (≤4 g in 24 hours but ≤1 g in 4 hours) may be administered at the discretion of the Investigator or delegate. Thyroid hormone replacement medication may be permitted if the participant has been on same stable dose for the last 3 months prior to the first dose of IP. Hormone replacement therapy and hormonal contraceptives will also be allowed.
15. Received an investigational drug within 30 days or 5 half-lives (whichever is greater) prior to the first dose of IP.
16. Has received any live vaccines (bacterial or viral) within 30 days prior to the first dose of IP or intend to receive a live vaccine during the study period.

    EXCEPTIONS: Vaccines allowed by the protocol include inactivated flu and COVID-19 vaccines in all participants. The recommended time intervals for administration of these vaccines are at least 7 days before the first dose of IP or 7 days after the last dose of IP.
17. Plans to donate or has donated ≥350 mL of blood (including blood products) within 28 days prior to the first dose of IP.
18. Plans to donate or has donated plasma within 7 days prior to the first dose of IP.
19. Female participant who is pregnant, breastfeeding, or plans to become pregnant or donate ova for in vitro fertilization during the study period and for 45 days following the last dose of IP or male participant who plans to donate sperm for in vitro fertilization during the study period and for 105 days following the last dose of IP.
20. The participant is considered to be vulnerable (e.g., cognitively impaired, or a person kept in detention).
21. The participant is an employee of the study site or has a family member or household member involved with the conduct of this study.
22. Any reason that in the opinion of the Investigator would lead to the inability of the participant to comply with the protocol.

Primary outcomes:
measure: Safety Outcome Measures (Adverse Events)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (Vital signs: Systolic Blood Pressure)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (Vital signs: Heart Rate)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (Vital signs: Respiratory Rate)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (Vital signs: Temperature)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (ECG QTCF Interval)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety outcome measures (Clinical Laboratory Parameters)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
measure: Safety Outcome Measures (Physical Exam)
timeFrame: From enrollment through 6 weeks for SAD participants, 7 weeks for MAD participants, and 7 weeks for Food Effect and Age Effect participants.
Secondary outcomes:
measure: Pharmacokinetics Outcome Measures (Cmax)
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacokinetics Outcome Measures (Tmax)
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacokinetics Outcome Measures (half-life (t1/2))
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacokinetics Outcome Measures (AUC0-t and AUC0-inf)
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacokinetics Outcome Measures (Total Plasma Clearance (CL))
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacokinetics Outcome Measures (Volume of Distribution (Vd))
timeFrame: Day 1 for the SAD, Food Effect and Age Effect parts and Days 1 and 14 for the multiple dosing parts.
measure: Pharmacodynamics Outcome Measures (Light Chain (LC) Stabilization)
timeFrame: From enrollment through Day 3 for SAD participants, through day 16 for MAD participants, through Day 3 for Age Effect participants.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
References: