A Phase 1 (First in Human) Randomized, Double-blind, Placebo-controlled SAD, MAD Study With Oral REM0046127

NCT04672135 | Completed Phase 1 DMC

• 1 other identifier: NSC20002
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 randomized double blind, first in human (FIH) study with the novel oral Alzheimer drug candidate REM0046127, which consists of two main parts, a single ascending dose (SAD) study with 7 cohorts followed by a multiple ascending dose (MAD) study with 2 cohorts.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (8)

• Adverse Events

  Number of Adverse Events either related or not related to treatment in the verum group in comparison to the placebo group

  SAD: from dosing to 72 hours after dosing. MAD: from the first dosing until 48 hours after the last dosing on day 7.

• SAD: Plasma Concentration including Peak Plasma Concentration (Cmax)

  The plasma concentration during 48 hours after the dosing.

  Plasma samples will be taken during SAD at baseline and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose.

• SAD: Plasma Concentration including Half-Life(t1/2)

  The plasma concentration during 48 hours after the dosing.

  Plasma samples will be taken during SAD at baseline and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose.

• SAD: Area under the Curve (AUC)

  The AUC between baseline and 48 hour safter dosing.

  Plasma samples will be taken during SAD at baseline and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose.

• MAD: Half-Life(t1/2) between Baseline and 48 hours after the last dosing.

  Half-Life(t1/2) between Baseline and 48 hours after the last dosing.

  Plasma samples will be taken pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours post-dose, pre-dose on Day 5 and on Day 7: 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours (Day 8) and 48 hours (Day 9).

• MAD: Plasma Concentration

  Peak Plasma Concentration (Cmax) between Baseline and 48 hours after the last dosing.

  Plasma samples will be taken pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours post-dose, pre-dose on Day 5 and on Day 7: 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours (Day 8) and 48 hours (Day 9).

• MAD: Area under the Curve (AUC)

  The AUC and steady-state volume of distribution(Vss) during the time interval from the first dose and 48 hour safterlast dose

  Plasma samples will be taken pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours post-dose, pre-dose on Day 5 and on Day 7: 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours (Day 8) and 48 hours (Day 9).

• Cerebrospinal Fluid (CSF) PK (MAD)

  In CSF the unbound brain/plasma partition coefficient (Kp,u) will be determined.

  CSF samples will be collected on the last day of dosing (Day 7) at approximately Tmax determined during SAD

Study Arms (2)

Study Drug

ACTIVE COMPARATOR

Each subject receives either a single dose (SAD) or a multiple dose (MAD) of REM0046127 as oral solution with a concentration of 100 mg/mL REM0046127. The starting dose for the first cohort in the SAD is 35mg up to a maximum of 2000mg at cohort 5. The starting dose for the MAD study is 0,75 of the Maximum Tolerated Dose (MTD) from the SAD.

Drug: REM0046127

Placebo

PLACEBO COMPARATOR

Each subject receives either a single (SAD) or multiple (MAD) dose of REM0046127 as oral solution with a concentration of 0 mg/mL REM0046127. The dose for each cohort is corresponding the amount of solution needed in the verum group.

Drug: Placebo

Interventions

REM0046127 DRUG

Oral solution: 100 mg/mL REM0046127

Study Drug

Placebo DRUG

Oral solution with 0 mg/mL REM0046127

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SAD/MAD: Young male subjects aged 18 to 45 years (limits included) willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason
• Elderly Cohorts: Elderly male and female (not of childbearing potential) subjects aged 55 to 80 (limits included) willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason.
• Women not of childbearing potential: Clinically significant abnormalities in screening laboratory tests, including:
• Surgically sterile (bilateral tubal ligation, hysterectomy), or
• Postmenopausal with last natural menses greater than 24 months
• Electrocardiogram without clinically significant pathologic abnormalities and with corrected QT interval (cQT) values lesser than 450 ms
• Normotensive as defined by Systolic Blood Pressure ≤ 150 mm Hg. Diastolic Blood Pressure ≤ 90 mm Hg without antihypertensive medication
• Body Mass Index (BMI) between 18 and 30 kg/m2.
• Body weight between 60 and 80 kg, inclusive
• Only for the elderly cohort of the MAD:
• Participants may be taking medication for non-serious chronic diseases, provided that the dose of these concomitant medications has been stable within the previous 2 months
• No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS)

You may not qualify if:

• Women of childbearing potential (WOCBP)
• Failure to perform screening or baseline examinations
• Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound the interpretation of safety observations according to the clinical assessment of the investigator (physician)
• Evidence of active infection requiring antibiotic therapy within 14 days prior to screening
• Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis
• History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin
• Seropositive for human immunodeficiency virus (HIV)
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen \[HbsAg\] or anti-Hepatitis C \[Hepatitis C Virus (HCV)\] antibody)
• Clinically significant abnormalities in screening laboratory tests, including:
• Absolute neutrophil count \< 1.4 x109
• Absolute lymphocyte count \< 1.2 x 109
• Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x the upper limit of normal (ULN)
• Lactate Dehydrogenase (LDH) \> 1.5 x ULN
• Total bilirubin level: Out of normal range 0-1.5 mg/dL
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min

Sponsors & Collaborators

• reMYND: lead
• NeuroScios GmbH: collaborator

Study Sites (1)

Medical University Vienna, Department of Clinical Pharmacology

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Nikola Helmberg, PhD

  NeuroScios GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: An independent statistician will provide the randomization list to an unblinded person at the site. The unblinded person prepares the medication for the subjects. The ready medication is handed over to the blinded investigator and the investigator will dose the blinded subjects. Randomization numbers will be kept secret until data base lock. After data base lock the results will be unblinded for final analysis.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Single Ascending Dose study with 6 Cohorts with 8 young male subjects each and 1 cohort with 4 male and 4 female subjects A Multiple Ascending Dose MAD study with 2 Cohorts: (Cohort 1: 10 young male subjects, Cohort 2: 6 elderly male and 6 elderly female (not of CBP) subjects.

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: December 17, 2020
• Study Start: November 9, 2020
• Primary Completion: April 1, 2022
• Study Completion: April 26, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)