First-in-Human Trial in Healthy Adult Volunteers to Evaluate Safety, Tolerability and PK of LAPIX Study Drug;LPX-TI641

• Sponsor: LAPIX Therapeutics Inc. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05853835
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 9
• Anticipated Duration (Months): 8
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

A Phase I First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate Safety, Tolerability, and Pharmacokinetics after Single and Multiple Oral Doses of LPX-TI641.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases; Multiple Sclerosis	Drug: LPX-TI641	Phase 1

Detailed Description

This is a Phase 1, single-center, randomized, single-blind, placebo-controlled single ascending doses/multiple ascending oral doses (SAD/MAD) study in healthy adult volunteers (HV). The Sponsor plans to enroll up to 60 healthy adult male and female volunteers in total irrespective of their race and ethnicity. The enrollment period is 6 months. But this period may be extended to complete the target enrollment. The study will follow a 4 + 4 design.

The SAD section will consist of six cohorts of four participants (3 treatment + 1 placebo) in each cohort (Total 24 HV). Additional cohorts may be added. The subjects in the SAD section are given a single oral dose and followed up for 14 days.

The MAD portion of the study will comprise of three cohorts of four participants (3 treatment

• 1 placebo) in each cohort (Total 12 HV). The participants are dosed daily for 14 days. Additional cohorts may be added. Each MAD cohort will be initiated only after a SAD cohort at a dose level higher than the planned MAD cohort has been cleared. The subjects in the MAD section are given the drug orally once daily for 14 days and followed up for 3 months.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The investigational drug blind will be maintained through a randomization schedule held by the dispensing pharmacist. The investigational drug blind shall not be broken by the site Investigator unless information concerning the investigational drug is necessary for the medical treatment of the subject. All study assessments and causality will be performed, if possible, prior to unblinding.
• Primary Purpose: Treatment
• Official Title: A Phase I First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate Safety, Tolerability, and Pharmacokinetics After Single and Multiple Oral Doses of LPX-TI641
• Anticipated Study Start Date: Jun 30, 2023
• Anticipated Primary Completion Date: Dec 15, 2023
• Anticipated Study Completion Date: Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort-1 First dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-2 Second dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-3 Third dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-4 Fourth dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-5 Fifth dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-6 Sixth dose of SAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-7 First dose of MAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-8 Second dose of MAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).
Experimental: Cohort-9 Third dose of MAD cohort (3 treatment + 1 placebo)	Drug: LPX-TI641; LAPIX Therapeutics Inc (LAPIX) has developed LPX-TI641, a small molecule for immune tolerance restoration/induction that is an orally bioavailable Tim family agonist (Tim-3 and Tim-4).

Outcome Measures

Primary Outcome Measures

1. To evaluate the safety and tolerability after single ascending oral doses of LPX-TI641 in healthy adult volunteers. [14 days]

   Proportion of subjects with AEs, SAEs and DLTs will be recorded.

2. To evaluate the safety and tolerability after multiple ascending oral doses of LPX-TI641 in healthy adult volunteers. [3 months]

   Proportion of subjects with AEs, SAEs and DLTs will be recorded.

Secondary Outcome Measures

1. To evaluate (Cmax) [1 day]

   To evaluate the Maximum observed plasma concentration (Cmax),after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers

2. To evaluate tmax [1 day]

   To evaluate the time to first occurrence of Cmax (tmax), after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

3. To evaluate AUC0-last [1 day]

   To evaluate Area under the plasma concentration-time curve from time 0 to the time last concentration measurement (AUC0-last) after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

4. To evaluate AUC0-24 [1 day]

   To evaluate Area under the plasma concentration-time curve from time 0 to 24 hr (AUC0-24)after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

5. To evaluate AUC0-∞ [1 day]

   To evaluate area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞), after single ascending oral dose of LPX-TI641 in healthy adult volunteers.

6. To evaluate %AUCextrap [1 day]

   To evaluate percentage AUC extrapolated (%AUCextrap) after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

7. To evaluate t1/2z [1 day]

   To evaluate terminal disposition phase half-life (t1/2z), after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

8. To evaluate Vz/F [1 day]

   To evaluate apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

9. To evaluate CL/F [1 day]

   To evaluate apparent clearance after extravascular administration (CL/F), after single ascending and multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

10. To measure Ctrough [14 days]

    To measure the minimal observed concentration within the dosing interval (Ctrough) after multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

11. To measure AUC [14 days]

    To measure AUC after multiple ascending oral doses of LPX-TI641 in healthy adult volunteers.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria: Healthy volunteers (SAD and MAD sections)

1. Healthy volunteers (HV) with no known acute or chronic medical conditions (respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, etc.) at the time of enrollment.

2. All male and non-pregnant females aged 18-55 years old irrespective of their race and ethnicity.

3. Body Mass Index (BMI) 18.0-30.0 kg/m2, inclusive at screening.

4. Clinical laboratory evaluations performed at screening, including the white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (T. Bili), lipase, blood urea nitrogen (BUN), creatinine, prothrombin time (PT), and partial thromboplastin time (PTT) are within acceptable normal reference ranges.

5. Subjects who are willing and able to adhere to study protocol requirements including but not limited to scheduled outpatient visits, inpatient hospital stay, laboratory tests, and 12-lead ECG.

6. Contraception - All subjects (male and female) must agree to use any two of the contraception methods listed below. This criterion must be followed from the time of the first dose of study medication for 6 weeks after the last dose in females and for 90 days after the last dose for males.

1. The following applies to all female volunteers with childbearing potential and female partners of male volunteers enrolled in the study.

2. Implantable progestogen-only hormone contraception associated with inhibition of ovulation.

1. Intrauterine device. iii. Intrauterine hormone-releasing system. iv. Bilateral tubal occlusion. v. Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: Oral Intravaginal Transdermal Injectable vi. Progestogen-only hormone contraception (oral or injectable) is associated with inhibition of ovulation.

2. Sexual abstinence -this is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated about the duration of the study and the preferred and usual lifestyle of the participant.

3. Cervical cap, diaphragm, or sponge with spermicide. b. The following applies to all male subjects in the study: i. Sexual abstinence- this is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated for the duration of the study and the preferred and usual lifestyle of the participant.

4. A combination of male condoms with either cervical cap, diaphragm, or sponge with spermicide (double-barrier methods).

5. Vasectomy

Exclusion Criteria: Healthy volunteers (SAD and MAD sections)

1. History of cancer treatment with either chemo or radiation therapy or both in the past 5 years before enrollment in the study.

2. COVID-19:

The subject has COVID-19 positive status (confirmed by clinical signs and symptoms and a positive SARS-CoV-2 NAAT result COVID test) at any time during the screening period.

OR

has had recent COVID-19 vaccination including a booster dose in the past 30 days

OR

has received anti-viral therapy intended to prevent COVID-19 such as paxlovid, remdesivir, molnupiravir, interferons, Anti-SARS-CoV-2 monoclonal antibodies, IVIG SARS-CoV-2, COVID-19 Convalescent plasma, etc. within the past 30 days

1. Blood loss of >250 mL or donated blood within 56 days, or donated plasma within 7 days of screening.

2. Recent vaccination with live attenuated vaccines such as influenza, MMR, Herpes zoster, varicella, yellow fever, Rotavirus vaccine, etc., or inactivated vaccines such as Hepatitis A, Rabies vaccine, etc. in the past 30 days.

3. The subject has participated in another investigational study involving any investigational product within 60 days, or 5 half-lives, whichever is longer, before the first oral dose of the study drug.

4. Pregnant or lactating women or women currently undergoing infertility treatments or women who intend to become pregnant during the time of study enrollment.

5. Involvement in the planning and conduct of the study (applies to CRO staff or staff at the study site).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Triumpharma	Amman		Jordan	11941

Sponsors and Collaborators

• LAPIX Therapeutics Inc.

Investigators

• Principal Investigator: Mustafa Mahmoud Shennak, Triumpharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: LAPIX Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT05853835
• Other Study ID Numbers: LPX641-101
• First Posted: May 11, 2023
• Last Update Posted: May 12, 2023
• Last Verified: May 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Sclerosis; Autoimmune Diseases

Study Results

No Results Posted as of May 12, 2023