Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001216808
Ethics application status
Approved
Date submitted
13/05/2021
Date registered
10/09/2021
Date last updated
10/09/2021
Date data sharing statement initially provided
10/09/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of EQ121 following oral single (Part 1) and multiple (Part 2) ascending dose administration in healthy subjects.
Scientific title
A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered EQ121 Following Single and Multiple Doses in Healthy Adult Volunteers
Secondary ID [1] 303963 0
EQ121-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 321581 0
Condition category
Condition code
Inflammatory and Immune System 319321 319321 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EQ121 capsule is an oral solid dosage form manufactured at strengths of 1 mg and 12 mg.
Each EQ121 capsule contains EQ121 drug substance; mannitol, pregelatinized starch and microcrystalline cellulose as diluents; croscarmellose sodium as disintegrant; colloidal silicon dioxide as glidant; and magnesium stearate as lubricant.
Part 1: Participants in Australia will receive a single dose of orally administered EQ121 or matching placebo in each cohort as follows: Cohort 1: 3 mg; Cohort 2: 6 mg; Cohort 3: 12 mg; Cohort 4: 24 mg; Cohort 5: 36 mg; Cohort 6: 60 mg; Cohort 7: 96 mg; and Cohort 8: 120 mg.
Part 2: Participants in Australia will receive orally administered EQ121 or matching placebo twice daily (twelve hours apart) for 14 days in each cohort as follows: Cohort 1: 12 mg; Cohort 2: 24 mg; Cohort 3: 36 mg; Cohort 4: 48 mg
participants will be monitored via clinical site staff recording and reporting all number of pills taken while confined. Participants will ingest investigational drug or placebo on an empty stomach and will have a total of three overnight stays (admission on Day -1 until 48 hours post-dose on Day 3) in Part 1. Participants should be instructed to come to the clinic with an empty stomach after overnight fasting (minimum 8 hours) and to avoid eating for 4 hour after dosing.
For participants in the Food Effect study, at their Day 8 visit: following an overnight fast of at
least 8 hours, participants will complete a test meal in 30 minutes or less. Study drug will be administered with 240 mL of water. No food will be allowed for at least 4 hours post-dose. Water is allowed as desired except for 1 hour before and 2 hours after study drug administration. The test meal will be a high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) breakfast. There is no requirement for fasting at the second daily dose during BID [Twice-daily (12 hours apart] dosing. Dosing commences 30minutes after start of high fat breakfast.
Adherence will be monitored via clinical site staff recording and reporting all number of pills taken while confined.
Food effect dose was chosen based upon the highest strength of the capsule formulation.
For participants in Cohort 3 (12 mg) of Part 1, after the completion of Cohort 3 and following a 7-day washout period, the same 8 participants will participate in the Food Effect study. At Day 8 visit.
Food effect is only being conducted in the SAD cohort 3 and not in any other cohort.
Intervention code [1] 320274 0
Treatment: Drugs
Comparator / control treatment
Placebo-controlled study.
Placebo LNK01001 capsule manufactured in strengths of 1mg and 12mg, corresponding filling volume is 85.00mg and 125.00mg respectively for trial use.
Composition of placebo LNK01001 capsules
• Mannitol- diluent
• Pregelatinized starch – diluent
• Microcrystalline cellulose – diluent
• Croscarmellose sodium- disintegrate
• Magnesium stearate – lubricant
Control group
Placebo

Outcomes
Primary outcome [1] 327189 0
To evaluate the safety and tolerability of EQ121 following oral administration in adult healthy volunteers. Adverse events will be coded using the most current version of the MedDRA® (Version 22.0 or higher).
Timepoint [1] 327189 0
Outcome is assessed by the incidence of adverse events during the study. Adverse events are assessed continuously for Single Ascending Dose from Day -1 through to Day 8 post-first dose, for Multiple Ascending Dose from Day -1 through to Day 21 post-first dose.
Primary outcome [2] 327318 0
To assess the safety and tolerability of EQ121 in adult, healthy participants. Outcome is assessed by Vital signs:
- blood pressure via automatic sphygmomanometer
- pulse rate calculated manually
- tympanic temperature via temperature probe
- ECG will be conducted via ECG machine
- Respiratory rate will be collected visually
- Physical examination via visible and verbal collection of data
Timepoint [2] 327318 0
Vital sign assessments will be done at
Part 1: Vital sign assessments will be done at Screening, Day -1, Day 1 multiple time points (0.0, 1, 2, 4, 6, 12 hrs) , Day 2 (24 hours), Day 3 (48 hours) and Day 8 post-first dose.
Part 2: Assessment will be done at screening, Day -1, Day 1 multiple time points (0.0, 1, 2, 4, 6, 12 hrs) Day 2 (24 hrs) Day 3 (48 hrs) & Day 8
SAD – Vitals: Screening, Day -1, Day 1 (0, 1, 2, 4, 12hrs), Day 2 (24hrs), Day 3 & Day 8
SAD FE – Vitals: Day 7, Day 8 (0, 1, 2, 4, 12hrs), Day 9, Day 10 and Day 15
MAD – Vitals: Screening, Day-1, daily from Day 1 through to Day 15 and Day 21
Primary outcome [3] 327319 0
To assess the safety and tolerability via clinical laboratory findings by collecting blood and urine samples:
- Hematology
- Biochemistry
-Coagulation
- Urinalysis
Timepoint [3] 327319 0
Single Ascending Dose: Clinical lab tests will be performed at Screening, on Day -1, Day 2, Day 3 and at the final visit (Day 8). Blood samples will be collected at pre-dose ( within 30 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3 ,4, 6, 8, 12, 24, 30, 36 and 48 hours post dose and at the end of the study.
Multiple Ascending Dose: Clinical lab tests will be performed at Screening, Day -1, pre-dose Day 1, Day 2, Day 5, Day 10 and Day 14 and Day 21 post-first dose
Secondary outcome [1] 394123 0
To evaluate the plasma pharmacokinetic parameters [Cmax, Tmax, T1/2, area under the curve (AUClast, and AUCinf)] of EQ121.
Timepoint [1] 394123 0
Part 1: Blood samples for the determination of EQ121 concentrations and corresponding pharmacokinetic (PK) analysis will be collected at pre-dose (within 30 min prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 30, 36, and 48 hours post-dose, and at end of study visit
Part 2: Blood samples for the determination of EQ121 concentrations and corresponding pharmacokinetic (PK) analysis will be collected at the following time points: Day 1 and Day 14 at pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours post morning dose.

Secondary outcome [2] 394464 0
To determine the effect of food on the pharmacokinetics of EQ121 following a single oral dose of EQ121. The food effect of EQ121 will be evaluated using Cmax, AUC0-t and AUC0-inf values.
The food effect of EQ121 will be evaluated using Cmax, AUC0-t and AUC0-inf values. Log- transformed PK parameters (Cmax, AUC0-t and AUC0-inf) will be analysed using an ANOVA model including terms for treatment condition (Fasted and Fed) as a fixed effect and participant as a random effect.
Timepoint [2] 394464 0
Blood samples will be collected at pre-dose on Day 8 (within 30 min prior to dosing) and at 0.5, 1,24, 6, 8, 12, 18, 24, and 48 hours post-dose, and at end of study visit.
Part 1 SAD FE Cohort 3 – collected at pre-dose on Day 8 (within 30 min prior to dosing) and at 0.5, 1,24, 6, 8, 12, 18, 24, and 48 hours post-dose, and at end of study visit.
Secondary outcome [3] 394599 0
To characterize the PK [Cmax, Tmax, T1/2, area under the curve (AUClast, and AUCinf)] of EQ121 following multiple oral doses in healthy adult Japanese volunteers. The samples being assessed are PK blood and PK Urine.
Timepoint [3] 394599 0
Blood samples for the determination of EQ121 concentrations and corresponding pharmacokinetic (PK) analysis will be collected at pre-dose (within 30 min prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 30, 36, and 48 hours post-dose, and at end of study visit
Secondary outcome [4] 396794 0
To evaluate urinary excretion and clearance (CLR, FE)
Timepoint [4] 396794 0
Urine PK samples will be collected at pre-dose on Day 1 and over the following intervals: 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, and 24 to 48 hours post-dose.
Secondary outcome [5] 397512 0
To evaluate the safety and tolerability of EQ121 following multiple oral doses in healthy adult Japanese volunteers. Safety assessments will include monitoring of AEs, vital signs (blood pressure, pulse rate, respiratory rate, and tympanic temperature), clinical laboratory findings, 12-lead electrocardiograms (ECGs), and physical examination findings. Adverse events and laboratory findings will be graded according to the Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007).
Timepoint [5] 397512 0
safety and tolerability will be assessed as below:
SAD- clinical labs
Screening, Day -1, Day 2, Day 3, Day 8
SAD FE- clinical labs
Day 7, Day 9, Day 10, Day 15
MAD – clinical labs
Screen, Day -1, daily from Day 1 to Day 6, daily from Day 8 to Day 12, Day 14, Day 21

Eligibility
Key inclusion criteria
1. Are capable of giving informed consent and complying with study procedures;
2. Healthy male or female participants, between the ages of 18 and 65 years, inclusive;
3. BMI of 18.0 to 32.0 kg per m2 inclusive and body weight not less than 50 kg;
4. Female participants must not be currently breast-feeding, and must meet one of the following criteria:
a. Surgically sterile for at least 3 months prior to Screening by one of the following means:
- Bilateral tubal ligation
- Bilateral salpingectomy (with or without oophorectomy)
- Surgical hysterectomy
- Bilateral oophorectomy (with or without hysterectomy)
b. Postmenopausal, defined as the following:
- Last menstrual period greater than 12 months prior to Screening without an alternative medical cause, AND
- Postmenopausal status confirmed by serum FSH concentration at Screening greater than 40 mIU per mL
c. Female subjects of childbearing potential:
• must not have a positive serum pregnancy test at Screening and must have a negative urine pregnancy test on admission
• must use at least one of the following protocol-specified highly effective methods of birth control, AND must agree to use barrier contraception (male condom) during heterosexual intercourse, from the time of Screening until at least 30 days after the last dose of study drug.
- Partner vasectomy (at least 6 months prior to Screening; vasectomized partner should be the sole partner of the female subject)
- Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal, injectable)
- Progestogen-only hormonal contraception (oral, injectable, implantable)
- Implantable device (implantable rod or intrauterine device)
5. Male participants must agree to utilize a highly effective method of contraception (condom) during heterosexual intercourse from clinic admission until 90 days following the last dose of study drug and must refrain from donating sperm for this same period. Vasectomized males do not need to use additional forms of contraception providing that the procedure was performed at least 12 weeks prior to Screening and an absence of sperm in the ejaculate has been documented. Total sexual abstinence may be considered acceptable at the discretion of the Investigator;
6. Considered healthy by the Investigator, based on participant’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Inability to attend all the study visits or comply with study procedures;
2. Evidence or clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
3. Hospital admission or major surgery within 3 months prior to Screening;
4. A history of drug abuse, or a positive test at Screening or at Admission for drugs of abuse;
5. A history of alcohol abuse according to medical history within 6 months prior to Screening (drinking 14 units of alcohol per week: 1 unit equals to 360 mL of beer, or 37 mL of spirits, or 120 mL of wine) at Screening or upon admission to the clinical site;
6. Positive screen for drugs of abuse or alcohol at Screening or at Admission;
7. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer), or any injectable prescription medications within 30 days or 10 half-lives (whichever is longer), of the first dose of study drug;
8. Taken an investigational drug within 3 months or 5 half-live, whichever is longer from the Screening date;
9. Any liver function panel analyte (LFT) value greater than 1.5 X upper limits of normal reference range (ULN) which includes AST, ALT, Bilirubin, Alkaline Phosphatase, and GGT at Screening or at Admission;
10. Any White Blood Cell (WBC), ANC, hemoglobin, or platelet count less than the lower limit of normal at Screening or at Admission that is clinically significant in the opinion of the Investigator;
11. Serum creatinine greater than upper limit of normal at Screening or Admission;
12. Any condition or finding that in the opinion of the Principal Investigator or designee would put the participant or study conduct at risk if the participant were to participate in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization through a randomization list prepared using a statistical software package by the study biostatistician.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
21/01/2021
Date of last participant enrolment
Anticipated
Actual
27/07/2021
Date of last data collection
Anticipated
26/11/2021
Actual
Sample size
Target
104
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19365 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 33828 0
4006 - Herston
Recruitment outside Australia
Country [1] 24053 0
New Zealand
State/province [1] 24053 0

Funding & Sponsors
Funding source category [1] 308343 0
Commercial sector/Industry
Name [1] 308343 0
EQRx, Inc
Country [1] 308343 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
EQRx, Inc
Address
50 Hampshire Street, Cambridge, MA 02139, USA
Country
United States of America
Secondary sponsor category [1] 309160 0
None
Name [1] 309160 0
Address [1] 309160 0
Country [1] 309160 0
Other collaborator category [1] 281742 0
Commercial sector/Industry
Name [1] 281742 0
Novotech (Australia) Pty Limited
Address [1] 281742 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW Australia - 2009
Country [1] 281742 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308317 0
Alfred Ethics Committee
Ethics committee address [1] 308317 0
Ethics committee country [1] 308317 0
Australia
Date submitted for ethics approval [1] 308317 0
Approval date [1] 308317 0
18/12/2020
Ethics approval number [1] 308317 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110286 0
Dr Richard Friend
Address 110286 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD, 4006, Australia.
Country 110286 0
Australia
Phone 110286 0
+61 07 3845 3620
Fax 110286 0
Email 110286 0
[email protected]
Contact person for public queries
Name 110287 0
Alexandra Davis
Address 110287 0
Q-Pharm Pty LTD 300 Herston Road, Herston, QLD, 4006
Country 110287 0
Australia
Phone 110287 0
+61 1800 243 733
Fax 110287 0
Email 110287 0
[email protected]
Contact person for scientific queries
Name 110288 0
Deepal Wakade
Address 110288 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW, Australia - 2009
Country 110288 0
Australia
Phone 110288 0
+61 2 9171 3219
Fax 110288 0
Email 110288 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.