Phase 1 Study Into Pharmacokinetics and Food Effect of Vapendavir in Healthy Participants and Participants With COPD

NCT05962645 | Completed Phase 1 FDA Drug

• 1 other identifier: ALT VPV-101
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Vapendavir (VPV) is potent virostatic antiviral agent active against all known enterovirus species. VPV binds to the viral capsid, thereby inhibiting viral attachment to the target cell and, independently, preventing release of viral RNA (ribonucleic acid) into the cell. Alt VPV-101 is meant to investigate vapendavir in patients with chronic obstructive pulmonary disease (COPD) who develop a rhinoviral infection. This is a Phase 1, open-label, unblinded study. The primary objective of this study is to characterize single and multiple dose (plus a loading dose) plasma PK profiles of VPV in healthy participants (Group A) and participants with COPD (Group B). Group A is an open-label, 2-sequence, and up to a 3-period, cross-over study to assess the single-dose PK parameters and safety of VPV. Healthy participants may opt to participate in only the first 2 periods, all 3 periods or BID dosing, but it is preferred that participants complete all 3 periods. Group B is an open-label, multi-dose investigation of VPV PK parameters and safety in participants with COPD. Post-dose, follow up will continue for a minimum of 14 days and a maximum of 30 days, depending on which Group the participant is in and which periods said participant completes. There is a target for up to 24 adult participants comprised of healthy participants and participants with COPD.

Conditions

COPD; Respiratory Disease; Lower Respiratory Disease; Pulmonary Disease; Healthy

Keywords

Placebo; Parallel; Interventional; Clinical trial; Clinical study; Placebo-Controlled; Phase 1

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic Analyses

  Plasma PK parameters for each participant will be estimated from the plasma concentrations of VPV over the sampling interval using standard non-compartmental PK analysis method. Additional PK parameters may be analyzed as appropriate. PK parameters will be summarized by group, treatment, period, and study day using descriptive statistics. Food effect on single-dose PK of VPV will be evaluated with fasted/fed status as a fixed effect and participant as a random effect. VPV Peak Plasma Concentration (Cmax) There will also be exploratory descriptive comparisons on PK parameters to explore any potential differences (e.g., healthy participants relative to participants with COPD, concomitant medication use, BMI, age).

  Through study completion, up to 3 weeks

• Pharmacokinetic Analyses

  Area under the plasma concentration versus time curve (AUC)

  Through study completion, up to 3 weeks

Study Arms (2)

Group A

EXPERIMENTAL

Healthy Participants (HP)

Drug: Vapendavir

Group B

EXPERIMENTAL

Participants with COPD

Drug: Vapendavir

Interventions

Vapendavir DRUG

This study will measure and compare how VPV is absorbed in the blood, broken down in the body and eliminated when two 250 mg VPV tablets (500mg) are given in three different ways: A single dose, once a day, under fasted conditions (without any food); twice a day, for 7 days; and a single dose, once a day under fed conditions, after consuming a high-fat meal.

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female participants, ≥ 18 and ≤ 55 years of age.
• Weight ≥ 45 kilograms (kg), females and ≥ 50 kilograms, males.
• Body mass index (BMI) within 18 to 32 kg/m2.
• Female participants of childbearing potential must have a negative pregnancy test and females of non-childbearing potential must be post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented FSH levels ≥ 40 mIU/mL or be surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy or tubal ligation) at least 3 months prior to dosing.
• If sexually active and/or of child-bearing potential (both females and males), must agree to abstinence or to use a highly effective forms of contraception ≥ 28 days prior to the first dose (females), during the study period (both males and females) and for 30 days (females) or 90 days (males) after the last dose.
• Examples: female participants: non-hormonal intrauterine device, double barrier; males (including those with a vasectomy): agree to use a condom and if a female partner of childbearing potential, use of at least one other contraceptive method; males must also agree not to donate sperm within 90 days after the last dose.
• Note: Refer to Section 12.5 for acceptable forms of contraception and timing required.
• If participant becomes pregnant during the study or follow-up period, they agree to transmit all relevant safety information regarding the pregnancy and outcomes to the Sponsor or their designee (female partners of male participants will be asked to consent to the same), as requested.
• Participants must be willing and able to understand and provide written informed consent.
• Participants who are able and willing to adhere to the study visit schedule and other protocol requirements.
• ≥ 40 and ≤ 75 years of age.
• BMI within 18 to 40 kg/m2.
• Documented diagnosis of clinically stable COPD (no exacerbations within 45 days prior to study-drug administration), consistent with one these GOLD categories:
• GOLD A: Minimally symptomatic, low risk of future exacerbations (ie, mMRC grade 0 to 1 or CAT score \< 10; 0 to 1 exacerbation per year and no prior hospitalization for exacerbation).
• GOLD B: More symptomatic, low risk of future exacerbations (ie, mMRC grade ≥ 2 or CAT score ≥ 10; 0 to 1 exacerbation per year and no prior hospitalization for exacerbation).

You may not qualify if:

• Any clinically significant illness and/or surgery within 4 weeks prior to dosing. This includes but is not limited to uncontrolled and clinically significant neurologic (including seizure disorders), cardiovascular, central nervous system (CNS), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic (including allergic skin rash), hematologic or endocrine disease, psychiatric disorder or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
• Any clinically significant finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking VPV, or a similar drug in the same class, or that might interfere with the conduct of the study.
• Note: It is the responsibility of the Investigator to assess the clinical significance of medical history or ongoing findings; however, consultation with the Medical Monitor may be warranted.
• The participant has current or recent (within 28 days) gastrointestinal disease significant enough in the opinion of the Investigator that it would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn), or any clinically significant gastric surgical intervention that could impact study drug absorption characteristics, in the opinion of the Investigator.
• History or current condition where repeat blood draws pose more than minimal risk to participant (eg, hemophilia, other severe coagulation disorders).
• Significantly impaired venous access and/or inability to tolerate repeat blood draws.
• Use of nicotine-containing products (including but not limited to electronic cigarettes, cigarettes, pipes, cigars, chewing tobacco, snuff, nicotine patch or gum) within 10 h of 1st dose in a Period, and within 2h (± 30 minutes) of any other dose, and unwillingness to adhere to requirements for duration of study.
• History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
• Positive drug or alcohol test at the screening.
• Pregnant (documented test) or nursing female participants at screening.
• Sexually active participants/female partner(s) of childbearing potential who are unwilling to utilize protocol-defined acceptable forms of contraception for duration of study and follow-up period.
• Participants using hormonal contraceptives and/or estrogen-based hormone replacement therapy via any route ≤ 14 days prior to dosing.
• Donation or loss of ≥ 450 mL of participant's blood volume (including plasmapheresis) or transfusion of any blood product within 45 days prior to first dose of study drug and agree not to donate for 45 days after completion of the study.
• Any clinically significant ECG abnormalities, including QT interval with Fridericia correction method (QTcF) ≥ 450 msec (males) or ≥ 470 msec (females) or PR interval outside the range of 120 to 220 msec, confirmed with1 repeat testing, at screening.
• A seated or semi-supine blood pressure outside of the range of 85 to 145 mm Hg for systolic and 50 to 95 mm Hg for diastolic confirmed on repeat testing within a maximum of 30 minutes, at screening.

Sponsors & Collaborators

• Altesa Biosciences, Inc.: lead

Study Sites (1)

Syneos Health Miami

Miami, Florida, 33136, United States

Location

Related Publications (15)

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• Wheaton AG, Cunningham TJ, Ford ES, Croft JB; Centers for Disease Control and Prevention (CDC). Employment and activity limitations among adults with chronic obstructive pulmonary disease--United States, 2013. MMWR Morb Mortal Wkly Rep. 2015 Mar 27;64(11):289-95.

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• Halpin DMG, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, Agusti AA, Vogelmeier CF. Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2021 Jan 1;203(1):24-36. doi: 10.1164/rccm.202009-3533SO.

  PMID: 33146552 BACKGROUND

• Altesa Biosciences Inc. Investigator's Brochure for Vapendavir v 10. 2023

  BACKGROUND

• Abzug MJ, Michaels MG, Wald E, Jacobs RF, Romero JR, Sanchez PJ, Wilson G, Krogstad P, Storch GA, Lawrence R, Shelton M, Palmer A, Robinson J, Dennehy P, Sood SK, Cloud G, Jester P, Acosta EP, Whitley R, Kimberlin D; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis. J Pediatric Infect Dis Soc. 2016 Mar;5(1):53-62. doi: 10.1093/jpids/piv015. Epub 2015 Apr 16.

  PMID: 26407253 BACKGROUND

• US Food and Drug Administration Center for Drug Evaluation and Research. Draft Guidance: Assessing the Effects of Food on Drugs in INDs and NDAs - Clinical Pharmacology Considerations Guidance for Industry. 2019.

  BACKGROUND

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  BACKGROUND

Related Links

• Sponsor website

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Respiration Disorders; Lung Diseases

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Wyatt, MD

  VP Medical Affairs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: July 27, 2023
• Study Start: May 19, 2023
• Primary Completion: December 12, 2023
• Study Completion: May 2, 2024
• Last Updated: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)