Clinical trial NCT05532293: Phase One Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of MSP008-22 in Healthy Adult Volunteers
Official title: A Phase I, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of MSP008-22 in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COVID-19
Keywords: Single Ascending Dose
Phase 1
Multiple Ascending Dose
randomised, double blind
MSP008-22
healthy volunteers
COVID-19
safety
tolerability
pharmacokinetics
Lead sponsor: Godavari Biorefineries Limited
Sponsor class: OTHER
First posted: 2022-09-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase I, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of the Investigational Product in Healthy Adult Volunteers
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase I clinical study of MSP008-22, the Investigational Medicinal Product (IMP). The current study is designed to evaluate the safety and tolerability and pharmacokinetics of single and multiple oral doses of the IMP (MSP008-22) in healthy volunteers.

Detailed description: MSP008-22 is a New Chemical Entity (NCE) that has demonstrated positive outcomes during in vitro and in vivo studies for COVID19.

This clinical study is planned as a double blind, randomised, placebo-controlled, combined clinical study of two parts: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies, respectively. Pharmacokinetic (PK) profile of the MSP008-22 will also be assessed in both parts of the study. The safety, tolerability and pharmacokinetic data and results obtained from this study will determine the potentially efficacious doses of the IMP (MSP008-22) in the subsequent efficacy studies in COVID-19 patients.

The SAD Part will consist of 5 cohorts of 8 healthy adult volunteers, each volunteer will be randomly (blinded) allocated to MSP008-22 or placebo (each cohort will consist of 6 volunteers receiving MSP008-22 and 2 volunteers receiving placebo). Five (5) dose levels (200, 400, 400 (BD), 600(BD) and 900 (BD) mg) of the investigational medicinal product are selected for oral administration. An additional cohort of 8 volunteers (6:2 MSP008-22 vs placebo) may be recruited into the SAD Part, if required.

The MAD Part will consist of 2 cohorts of 8 healthy adult volunteers, each volunteer will be randomly (blinded) allocated to MSP008-22 or placebo (each cohort will consist of 6 volunteers receiving MSP008-22 and 2 volunteers receiving placebo). Two (2) dose levels (600 (BD) and 900 (BD) mg) of the investigational medicinal product are selected for oral administration.

An additional cohort of 8 volunteers (6:2 MSP008-22 vs placebo) of lower doses (less than 900 mg BD) may be recruited into the MAD Part, if required.

Additional Volunteers will be enrolled to replace dropouts (volunteers withdrawing consent from the study for reasons other than safety). Additional volunteers will also be enrolled if a Cohort needs to be repeated.

Healthy adult volunteers eligible for participations in the study will be enrolled as study participants. They will be randomly assigned to the IMP (MSP008-22) and placebo arm of the SAD/MAD part.

A total Seventy Two (72) healthy adult volunteers volunteer (48 in the SAD part including additional cohort if required and 24 in MAD part including additional cohort if required).

Between each cohort, an interim analysis of PK, safety and tolerability will be performed. The available data will be evaluated by an independent Drug Safety Monitoring Board (DSMB). Once a dose level is judged to be safe, the DSMB will allow the escalation to the next cohort.

Both the Investigator and study participants will remain blinded to the treatment administered (drug or placebo) till the final results of the study are obtained.

DSMB will provide recommendations about stopping, modifying or continuing the study. Decision to escalate to next dose level/ Cohort, will be based on interim analysis of pharmacokinetic data, 36-hr post-dose, and 30-days post dose safety follow-up.

The dosing and the conduct of study between the cohorts will be staggered by approximately 2 to 4 weeks.

Safety evaluation during both the SAD \& MAD pars of the clinical study will include adverse events, clinical laboratory/ pathological test results, electrocardiogram (ECG), and measurement of vital signs

Pharmacokinetics will be determined at pre-dose, and 30 min, 1h, 2h, 4h, 8h, 12h, and 24, post-dose, and 36 hrs post-dose on Day 2, for the SAD Part of the Study.

Pharmacokinetics will be determined at pre-dose, and 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, of Day 1 and Day 7, at pre-dose on Days 2-6 and 36 hrs post final dose of Day 7 for the MAD Part of the Study.

Eligibility criteria: Inclusion Criteria:

Volunteers will be enrolled in the study when the following inclusion criteria will be met:

1. Should be healthy adult volunteer in the age range of 18-50 years old (both inclusive).
2. Should be healthy adult volunteers, with a BMI 18-30 kg/m2 (both inclusive).
3. Volunteer is able to read the volunteer information sheet, to understand information about the study and willing to sign the informed consent voluntarily.
4. Healthy as determined by pre-study medical history, physical examination, vital signs, haematology, chemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range, or showing no clinically relevant deviations, as judged by the Investigator.
5. Negative tests for Hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV) and human immunodeficiency virus (HIV)-l and HIV -2 antibody at screening.
6. Clinical laboratory test results clinically acceptable at screening and admission.
7. Negative screen for alcohol and drugs of abuse at screening and admission.
8. Non-smokers or ex-smokers (must have ceased smoking \>12 months prior screening visit). If a former smoker, reason for stopping smoking to be investigated.
9. The volunteer must agree to comply with the drawing of blood samples for the PK assessments.
10. The volunteer is willing and able to comply with all testing and requirements defined in the protocol.
11. The volunteer is willing and able to remain at the study site for the duration of the confinement period as per the protocol requirements or if exceeded, on Investigator's discretion, if exceeded and return for the outpatient visit.

    If female:
12. Woman with no childbearing potential by reason of surgery or at least 1-year post-menopause (Le., 12 months post last menstrual period), or menopause confirmed by follicle-stimulating hormone (FSH) testing;
13. If of childbearing potential, using an effective nonhormonal method of contraception· (intrauterine device or intrauterine system; condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that volunteer) for all the duration of the study and up to one month after the last Investigational medicinal product (IMP) administration;
14. Negative serum pregnancy test at screening and negative urine pregnancy test on admission of each treatment period (women of childbearing potential only);

    If Male
15. Using an effective method of contraception (condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomy) throughout the study and up to one month after the last IMP administration

Exclusion Criteria:

Volunteers meeting any of the following criteria will be excluded from this clinical study:

1. The volunteer has any relevant deviations from normal in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the Investigator.
2. The volunteer has had a clinically significant illness or conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs, within 30 days of Check-in for the study.
3. The volunteer has a clinically relevant history or presence of significant respiratory, neurological, hepatic, renal, endocrine, cardiovascular, neurological, gastrointestinal, pulmonary, haematological, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue, lymphatic or metabolic disease or disorders.
4. The volunteer has a significant infection or known inflammatory process on screening or admission.
5. The volunteer has acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission.
6. The volunteer has a clinically significant surgical history
7. The volunteer has used any prescription medication within 14 days of dosing or over-the-counter (OTC) medication within 48 h of dosing or intends to use any prescription medication or OTC medication during the study that may interfere with the evaluation of study medication.
8. The volunteer has had used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion
9. The volunteer has consumed alcohol, caffeine or xanthine-containing products 48 h before dosing or intends to use any of these products during the study.
10. The volunteer has consumed grapefruit, grapefruit juice, or grapefruit-containing products 7 days before dosing or intends to use any of these products during the study.
11. The volunteer has a history of substance abuse or a positive ethanol breath test, urine cotinine, or urine drug screen at screening or at check-in.
12. The volunteer has a positive HIV test at the Screening Visit.
13. The volunteer has received an investigational drug within 30 days of Check-in.
14. Use of any investigational drug within 30 days, or 5 half-lives, whichever is longer, prior to the planned first drug administration.
15. The volunteer has participated in more than 2 clinical studies within the 12 months prior to screening.
16. The volunteer has used any investigational drug or participated in any clinical trial within 90 days prior to dosing in this study.
17. The volunteer has donated or lost a significant volume of blood (\>450 mL) within 4 weeks prior to the study.
18. The volunteers have a history of hyperemesis
19. The volunteer is unwilling to reside in the study site for the duration of the study or to cooperate fully with the investigator or site personnel.
20. The volunteer has an AST/ALT or total bilirubin greater than the ULN. One repeat test will be allowed.
21. The volunteer has a history of relevant atopy or drug hypersensitivity or known intolerance to the inactive ingredients in the IMP.
22. The volunteer has clinically relevant abnormalities found in physical examination, vital signs measurements, laboratory safety tests or ECG, e.g. QTc according to Bazett: QTc \> 450ms, PQ \> 220ms, QRS \> 120ms
23. The volunteer has supine pulse rate not within 45 to 90 beats per minute and/or supine blood pressure Systolic \< 90 \>145 mmHg and diastolic \< 40 \> 95 mmHg.
24. Surgery or trauma with significant blood loss within 2 months before the planned screening for the trial.
25. Any social and medical condition that would jeopardize the volunteer's appropriate participation in this study.
26. Have any medical dietary restrictions.
27. Cannot communicate reliably with the Investigator(s)
28. Are unlikely to co-operate with the requirements of the study.
29. Known or suspected of not being able to comply with the trial protocol and/or clinical unit restrictions.
30. Are unwilling or unable to give written informed consent.
31. Volunteer is an employee of the Sponsor, the Investigator or the Institution of the Investigator.

    If female:
32. Pregnancy or breast-feeding.
33. Woman of childbearing potential not using an accepted effective contraceptive method or using oral contraceptives

    If male:
34. Not using an accepted effective method of contraception.

Primary outcomes:
measure: Number of participants with adverse events [Time Frame- ]
timeFrame: 30 days post last dose for each cohort
measure: Incidence of serious adverse events (SAEs) by relation to the IMP (related/not related)
timeFrame: 30 days post last dose for each cohort
measure: Percentage of volunteers who experience at least 1 Treatment Emergent Adverse Event (TEAE)
timeFrame: 30 days post last dose for each cohort
measure: Percentage of volunteers who discontinue due to an Adverse Event (AE).
timeFrame: 30 days post last dose for each cohort
measure: Percentage of volunteers who meet the markedly abnormal criteria for safety laboratory tests at least once post dose.
timeFrame: 7 days post last dose for each cohort
measure: Percentage of volunteers who meet the markedly abnormal criteria for vital sign measurements at least once post dose
timeFrame: 7 days post last dose for each cohort
measure: Percentage of volunteers who meet the markedly abnormal criteria for safety electrocardiogram (ECG) parameters at least once post dose.
timeFrame: 7 days post last dose for each cohort
Secondary outcomes:
measure: Plasma Cmax
timeFrame: post-dose in Single ascending Dose trial & post dose on days 1 & 7 in Multiple ascending dose part of the trial
measure: Plasma Tmax
timeFrame: post-dose in Single ascending Dose trial & post dose on days 1 & 7 in Multiple ascending dose part of the trial
measure: Plasma AUC0-t
timeFrame: Single ascending Dose
measure: Plasma AUC0-inf
timeFrame: Single ascending Dose
measure: Plasma AUC0-tau
timeFrame: post dose on days 1 & 7 in Multiple ascending dose part of the trial
measure: Plasma AUC0-t
timeFrame: post dose on day 7 in Multiple ascending dose part of the trial
measure: Plasma Kel
timeFrame: in Single ascending Dose trial & post-dose on day 7 in Multiple ascending dose part of the trial
measure: Plasma t1/2
timeFrame: in Single ascending Dose trial & post dose on day 7 in Multiple ascending dose part of the trial
measure: Plasma Ctrough
timeFrame: on days 2 & 6 in Multiple ascending dose part of the trial
measure: Plasma Racc
timeFrame: post dose on days 1 & 7 in Multiple ascending dose part of the trial
Other outcomes:
Locations:
city: Mumbai
country: India
facility: K. J. Somaiya Hospital & Research Centre, Somaiya Ayurvihar Complex, Eastern Express Highway, Sion East
state: Maharashtra
Study officials:
affiliation: Clinexel Life Sciences Pvt. Limited
name: Deepa Arora, MD
role: STUDY_DIRECTOR
References: