Safety Study of SLV213 for the Treatment of COVID-19.

NCT06146374 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 22-002775N93022D00016
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1 double blind, placebo-controlled study will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses (MAD) of SLV213 in healthy male and female participants, 18-65 years of age. This study will help to select the most likely suitable dose (e.g., at Maximum Tolerated Dose \[MTD\]) for the treatment of patients with COVID-19 in a pivotal study. This phase 1 double blind, placebo-controlled study will consist of three sequential cohorts of 12 participants each (8 SLV213 and 4 placebo), at doses of 400 mg every 12 hours (Q12h), 600 mg Q12h, and 800 mg Q12h administered orally (PO) for 7 days. After each cohort, a Safety Review Committee (SRC) will evaluate the safety of the regimen before proceeding to dose the next cohort. Randomization will occur into the respective cohorts as above. Upon meeting the Inclusion/Exclusion criteria, subjects will begin treatment with SLV213 or placebo per their assigned cohort. The primary objective is to evaluate the safety and tolerability of multiple ascending doses of SLV213 for 7 days in healthy participants.

Conditions

COVID-19

Keywords

Coronavirus; Covid-19; Double Blind; Healthy Volunteers; Multiple Ascending Dose; Phase 1; Placebo Controlled; Randomized; SLV213

Outcome Measures

Primary Outcomes (13)

• Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity

  The number of participants who experienced at least one unsolicited TEAE of any relatedness are summarized by the maximum severity recorded. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE.

  Day 1 through Day 28

• Frequency of Related Treatment-Related TEAEs

  The number of participants who experienced at least one related unsolicited TEAE of any severity. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE. A TEAE is considered related if there is a reasonable possibility that the study intervention caused the TEAE, or there is a temporal relationship between the study intervention and event.

  Day 1 through Day 28

• Frequency of Serious Adverse Events (SAEs)

  The number of participants who experienced at least one SAE throughout the course of the study. An AE is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or * A congenital anomaly/birth defect.

  Day 1 through Day 28

• Frequency of Laboratory AEs by Maximum Severity

  The number of participants who experienced at least one laboratory AE of any relatedness are summarized by the maximum severity recorded. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

  Day 1 through Day 28

• Frequency of Treatment-Related Laboratory AEs

  The number of participants who experienced at least one related laboratory AE of any severity. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

  Day 1 through Day 28

• Frequency of Electrocardiogram (ECG) AEs by Maximum Severity

  The number of participants who experienced at least one ECG AE of any relatedness are summarized by the maximum severity recorded. Graded ECG parameters include PR Internal and QTcF Interval.

  Day 1 through Day 28

• Frequency of Treatment-Related ECG AEs

  The number of participants who experienced at least one related ECG AE of any severity. Graded ECG parameters include PR Internal and QTcF Interval.

  Day 1 through Day 28

• Frequency of Early Terminations or Withdrawals Due to Treatment-Related TEAEs

  The number of participants who terminated early or were withdrawn due to a treatment-related TEAE. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

• Frequency of TEAEs

  The number of participants who experienced at least one TEAE of any severity. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

• Frequency of Grade 3 or Higher Laboratory AEs

  The number of participants who experienced at least one Grade 3 (severe) or higher laboratory AE. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

• Frequency of Grade 3 or Higher Vital Signs AEs

  The number of participants who experienced at least one Grade 3 (severe) or higher vital signs AE. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

• Frequency of Grade 3 or Higher ECG AEs

  The number of participants who experienced at least one Grade 3 (severe) or higher ECG AE. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

• Frequency of Participants Who Received All Oral Medication Doses

  The number of participants who received all doses of study product. This outcome is used to assess the tolerability of the study treatment.

  Day 1 through Day 28

Secondary Outcomes (29)

• Maximum Concentration (Cmax) of SLV213 in Plasma After Dose 1

  0 h through 12 h post dose 1

• Minimum Concentration (Cmin) of SLV213 in Plasma After Dose 1

  0 h through 12 h post dose 1

• Time of Maximum Concentration (Tmax) of SLV213 in Plasma After Dose 1

  0 h through 12 h post dose 1

• Time of Minimum Concentration (Tmin) of SLV213 in Plasma After Dose 1

  0 h through 12 h post dose 1

• Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to Infinity (AUC0-inf) of SLV213 in Plasma After Dose 1

  0 h through 12 h post dose 1

Study Arms (3)

Group 2

EXPERIMENTAL

600mg (6x 100mg capsules) of SLV213 (N=8) or placebo (N=4) administered orally every 12 hours for 7 days to healthy male and female participants 18-65 years of age.

Other: Placebo for SLV213; Drug: SLV213

Group 3

EXPERIMENTAL

800mg (8x 100mg capsules) of SLV213 (N=8) or placebo (N=4) administered orally every 12 hours for 7 days to healthy male and female participants 18-65 years of age.

Other: Placebo for SLV213; Drug: SLV213

Group1

EXPERIMENTAL

400mg (4x 100mg capsules) of SLV213 (N=8) or placebo (N=4) administered orally every 12 hours for 7 days to healthy male and female participants 18-65 years of age.

Other: Placebo for SLV213; Drug: SLV213

Interventions

Placebo for SLV213 OTHER

Microcrystalline cellulose in a size 1 orange hard gelatin capsule.

Group 2; Group 3; Group1

SLV213 DRUG

SLV213 drug substance (K777) is 4-methylpiperazine-1-carboxylic acid, a vinyl sulfone cysteine protease inhibitor for the treatment of subjects infected with SARS-CoV-2. SLV213 is a white powder substance without excipients or stabilizer that will be packed into gelatin capsules which has been demonstrated to exhibit broad inhibitory properties against host cathepsins (e.g., Cathepsin L).

Group 2; Group 3; Group1

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Able to understand and willing to be available for all study visits and comply with all study procedures including Lifestyle Considerations throughout the study.
• Male and Female individuals, age 18-65 inclusive at time of enrollment.
• Good general health by medical history (MH), physical examination (PE), and vital signs (VS), clinical laboratory tests and Electrocardiogram (ECG) within normal reference range.
• Note 1: Lab exceptions include: lab test values that are within Grade 1 range per the Toxicity Table (Appendix A) are acceptable if not considered to be clinically significant by the investigator (PI, sub-investigator, or authorized clinician), with the exception of liver function tests (LFT) (transaminases Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), alkaline phosphatase (AP), total and direct bilirubin, serum creatinine, estimated glomerular filtration rate (eGFR) per the CKD-EPI formula, and urine protein, which must be within the laboratory normal reference range.
• Note 2: Screening laboratory values that fall outside the laboratory normal reference ranges and the ranges are not listed within the Toxicity Table (Appendix A) (e.g., decrease activated partial thromboplastin time (aPTT)) that are deemed Not Clinically Significant by the PI will be acceptable.
• Ability to take oral medication and be willing to adhere to the dosing regimen.
• Women of childbearing potential1 must have practiced or use true abstinence2 or use at least one acceptable primary form of contraception3 for specified periods4 before, during and after dosing.
• Note 1: Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, salpingectomy, tubal ligation, or Essure placement with a history of documented radiological confirmation test at least 90 days after the procedure).
• Note 2: True abstinence is 100% of the time without sexual intercourse (the male's penis enters the female's vagina). Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Note 3: Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant receiving the study product, tubal ligation, non-hormonal, intrauterine device, (and if in a monogamous relationship with a male partner who uses a barrier method without spermicide) Note 4: Specified periods include at least 30 days prior to screening, during the period between screening and completion of dosing, and until at least 30 days following receipt of the last dose of study product.
• Women of childbearing potential must have a negative serum Beta-human chorionic gonadotropin (HCG) pregnancy test at screening and a negative urine HCG pregnancy test at check-in (Day-1) within 24 hours before receiving the initial study product.
• Male participants receiving the study product must use acceptable contraception and refrain from donating sperm from the day of first dose until 30 days after the last dose or be vasectomized.1 Note 1: Acceptable contraception includes abstinence from intercourse with a female of childbearing potential or use of a male condom without spermicide when engaging in any activity that allows for the passage of ejaculate to a female during the intervention period and for at least 30 days after ending study dosing, or surgical sterilization for 180 days or more.
• Willing to avoid excessive physical exercise starting within 48 h prior to dosing and until discharge from the CTU on Day 9.
• No history of acute febrile or infectious illness for at least 7 days prior to the administration of study drug.

You may not qualify if:

• Pregnant or lactating.
• History of any chronic disease that may increase risk to subject or interfere with endpoint assessment1:
• Note 1: With the exception of stable chronic medical conditions that do not require prescribed oral or injectable medications (e.g., Type 2 diabetes managed by diet only).
• History of bradycardia, orthostatic hypotension or orthostatic tachycardia, Long COVID or history of dysautonomia.1 Note 1: Exception is sinus bradycardia (HR \<60 bpm) in healthy participants (e.g., conditioned athletes) could be enrolled per investigator's clinical judgement.
• Known history of a clinically significant food or drug allergy/hypersensitivity including known allergy/hypersensitivity to ingredients of the study drug or placebo.
• Current seasonal allergies with ongoing symptoms for more than a week prior to dosing requiring glucocorticoids and/or frequent use of antihistamines for treatment.
• History of any clinically significant disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to initiation of administration of study product(s).
• History of any psychiatric condition that has required hospitalization in the last 12 months or subject is considered psychologically unstable by the investigator.
• History of any substance use disorder or positive urine drug screening (UDS) test for illicit substances at Screening or Check-in (Day -1)1.
• Note 1: Any approved medical use of amphetamines, barbiturates, benzodiazepines, cannabis, tricyclic antidepressants and opiates will not be acceptable.
• History of alcoholism or of binge1 or heavy alcohol drinking2 at any time in the 6 months before study product administration or positive urine alcohol test at Screening or Check-in (Day -1).
• Note 1: Binge drinking is defined as 5 or more drinks during a single occasion if male, or 4 or more if female.
• Note 2: Heavy drinking of alcohol is defined as consumption of more than 14 drinks of alcohol per week if male, or more than 7 drinks if female.
• History of \>/=10 pack-years of nicotine product1 consumption in the 5-year period before screening, or positive urine cotinine screen at Check-in (Day -1)2.
• Note 1: Nicotine products include cigarettes, e-cigarettes, pipe, cigar, chewing tobacco, nicotine patch.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Altasciences Inc - Kansas City

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

N-pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: George A. Saviolakis, MD, PhD
• Organization: DynPort Vaccine Company, a GDIT Company

George.Saviolakis@gdit.com

301-835-4101

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: November 24, 2023
• Study Start: April 9, 2024
• Primary Completion: July 8, 2024
• Study Completion: July 8, 2024
• Last Updated: July 22, 2025
• Results First Posted: July 22, 2025

Record last verified: 2023-12-26

Locations

US (1)