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A Study of LAM-002A for the Prevention of Progression of COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04446377
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : July 17, 2020
Sponsor:
Collaborator:
Yale University
Information provided by (Responsible Party):
AI Therapeutics, Inc.

Brief Summary:
This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care in an outpatient setting.

Condition or disease Intervention/treatment Phase
COVID-19 Disease Drug: Apilimod Dimesylate Capsule Other: Placebo Phase 2

Detailed Description:

This is a Phase II randomized, double-blind, placebo-controlled, clinical study to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection and mild symptoms who are receiving standard supportive care in an outpatient setting.

Study eligibility will be assessed during screening. All study participants must sign a written informed consent and satisfy the inclusion and exclusion criteria for the study. Confirmation of SARS-CoV-2 infection via an RT-PCR test, medical history, and current medication will be assessed for each consenting participant at screening.

Study participants will be randomized in a 1:1 ratio, to receive study therapy (either LAM-002A, 125 mg [5 capsules/dose]) PO BID or placebo [5 capsules/dose] PO BID) for 10 days. Participants who experience an adverse event (AE) considered to be related to study therapy may have a decrease in study dose of LAM-002A to 100 mg [4 capsules/dose]) PO BID or placebo [4 capsules/dose] PO BID). After the start of treatment on Day 1, participants will be followed at Days 4,6,8,11,22, and 28. Participants can withdraw from the study therapy or study participation at any time.

The study will incorporate an interim safety analysis after the first 30 participants (15 on LAM-002A and 15 on placebo) have completed treatment and have been followed up for 11 days post-first dose. Recruitment and randomization will continue while this analysis is conducted. Recommendations from an independent Data Safety Monitoring Board (DSMB) will be used for decisions of early termination or study design adaptations.

Non-parametric and parametric statistical analysis will be conducted, as appropriate. For the comparison of the LAM-002A active arm and the control arm for the primary endpoint and secondary endpoints of drug effect, appropriate methods will be employed. Baseline subject characteristics, study therapy administration/compliance, safety, supportive care administration, and pharmacokinetics will be analyzed descriptively.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blinded
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-Blind, Placebo-Controlled Study of LAM-002A for the Prevention of Progression of COVID-19
Actual Study Start Date : July 15, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : January 31, 2021

Arm Intervention/treatment
Experimental: LAM-002A
LAM-002A (Apilimod Dimesylate) 125mg in five 25-mg capsules BID for 10 days
Drug: Apilimod Dimesylate Capsule
LAM-002A is formulated in capsules containing 25 mg of apilimod dimesylate. The capsule is Swedish orange, Size 0.

Placebo Comparator: Placebo
(microcrystalline cellulose) in 5 capsules BID for 10 days
Other: Placebo
Microcrystalline cellulose in Swedish orange, Size 0 capsules




Primary Outcome Measures :
  1. Viral Load Change [ Time Frame: 4 Days ]
    To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 4


Secondary Outcome Measures :
  1. Viral Load Change [ Time Frame: 6 Days ]
    To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 6, compared between the LAM-002A arm and the placebo arm.

  2. Viral Load Change [ Time Frame: 8 Days ]
    To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 8, compared between the LAM-002A arm and the placebo arm.

  3. Viral Load Change [ Time Frame: 11 Days ]
    To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 11, compared between the LAM-002A arm and the placebo arm.

  4. Viral Load Change [ Time Frame: 28 Days ]
    To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 28, compared between the LAM-002A arm and the placebo arm.

  5. Viral Load AUC [ Time Frame: 28 Days ]
    To evaluate the anti-viral efficacy of LAM-002A in participants with COVID-19 as difference in SARS-Cov-2 viral load as measured by qRT-PCR from nasopharyngeal samples based on AUC (days1-28), between LAM-002A arm and placebo arm.

  6. Safety and Tolerability measured in proportion of TEAEs [ Time Frame: 28 Days ]
    The proportion of LAM-002A treated patients who develop treatment-emergent adverse events (TEAEs) compared to placebo. TEAEs will be defined as AEs that occur on or after the date and time of study drug administration, or those that first occur pre-dose but worsen in frequency or severity after study drug administration. AEs will be followed up until complete resolution or until the Principal Investigator (PI) or Sub-Investigator deems it safe to discontinue followup.


Other Outcome Measures:
  1. Clinical Efficacy in prevention of hospitalization or death [ Time Frame: 28 Days ]
    To evaluate the efficacy of LAM-002A in preventing COVID-19 disease progression in participants who have proven infection with SARS-CoV-2 virus as determined by a molecular test and who have mild manifestations of COVID-19 and less than or equal to 4 days of symptoms; disease progression is defined as occurance of death or hospitalization at day 28.

  2. Oxygen Saturation [ Time Frame: 1 Days ]
    To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.

  3. Oxygen Saturation [ Time Frame: 4 Days ]
    To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.

  4. Oxygen Saturation [ Time Frame: 6 Days ]
    To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.

  5. Oxygen Saturation [ Time Frame: 8 Days ]
    To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.

  6. Oxygen saturation [ Time Frame: 11 Days ]
    To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.

  7. Clinical Status defined by ordinal scale [ Time Frame: 28 days ]

    Change in COVID-19 clinical status as defined by the ordinal scale, of participants treated with LAM-002A as compared with placebo at Day 28, in participants who become hospitalized and continue LAM-002A/placebo treatment, based on the following scores:

    1. Not in the hospital
    2. Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula)
    3. Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-ICU)
    4. Hospitalized, in the ICU, on invasive ventilation or ECMO
    5. Dead For participants (who have the same ordinal score), control versus experimental arms will be compared based on percentage of participants at each score.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Presence of SARS-CoV-2 infection confirmed by polymerase chain reaction (RT-PCR) test.
  2. Presence of great than or equal to ≥1 of the following COVID-19-related symptoms indicating mild disease: fever (temperature ≥100.4), anosmia, cough, sore throat, gastrointestinal complaints (e.g. vomiting, or diarrhea)
  3. Symptom onset less than or equal to ≤ 4 days.
  4. For female participants of childbearing potential, a negative urine (or serum) pregnancy test.
  5. For female participants of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until greater than or equal to ≥30 days after the final dose of study therapy. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥50 years with amenorrhea for ≥6 months).
  6. For male participants who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥30 days after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥90 days after administration of the final dose of study therapy. Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
  7. Willingness and ability of the participant to ingest study drug capsules.
  8. Willingness of the participant to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, study procedures, and study restrictions.
  9. Evidence of a personally signed informed consent indicating that the participant is aware of the nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Exclusion Criteria:

  1. Respiratory rate greater than or equal to ≥20 breaths per minute.
  2. Oxygen saturation by pulse oximetry less than or equal to ≤93 percent % on room air or requirement for supplemental oxygen to maintain oxygen saturation greater than >93 percent %.
  3. Total NEWS score greater than or equal to ≥6 or presence of a score of 3 on any of the individual NEWS parameters.
  4. Radiographic evidence of pulmonary infiltrates (clinical X-ray within 2 days of referral)
  5. Hepatic profile showing any of the following:

    • Serum alanine aminotransferase (ALT) greater than >5 × upper limit of normal (ULN) (CTCAE Grade greater than or equal to ≥3).
    • Serum aspartate aminotransferase (AST) greater than >5 × ULN (CTCAE Grade greater than or equal to ≥3).
    • Serum bilirubin greater than >1.5 × ULN (CTCAE Grade greater than or equal to ≥2).
  6. Renal profile showing an estimated creatinine clearance (eClCR) less than <30 mL/minute (with eClCR to be calculated by the method at the laboratory performing the serum creatinine test).
  7. Presence of a cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
  8. Significant cardiovascular disease (e.g. myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 1 month prior to start of study therapy; unstable angina; symptomatic peripheral vascular disease; CTCAE Grade greater than or equal to ≥2 congestive heart failure; or uncontrolled CTCAE Grade greater than or equal to ≥3 hypertension (diastolic blood pressure greater than or equal to ≥100 mmHg or systolic blood pressure greater than or equal to ≥160 mmHg) despite antihypertensive therapy.
  9. Significant screening ECG abnormalities, including atrial fibrillation/flutter, 2nd degree atrioventricular (AV) block type II, 3rd-degree AV block, Grade greater than or equal to ≥2 bradycardia, or corrected QT (QTc by Fridericia [QTcF]) greater than >480 msec (Grade greater than >1).
  10. Gastrointestinal disease (e.g. gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that might interfere with drug absorption or with interpretation of gastrointestinal AEs.
  11. Pregnancy or breastfeeding.
  12. Prior solid organ transplantation.
  13. Use within 5 days prior to randomization of an approved or investigational therapy intended to treat COVID-19 (e.g. remdesivir, , anti-interleukin [IL]-6 antibodies, therapeutic anti-SARS CoV-2 antibodies or post-convalescent plasma, anti- SARS CoV-2 vaccine, Bruton tyrosine kinase [BTK] inhibitor), use within 3 months of chloroquine or hydroxychloroquine. Note: participants are not precluded from undergoing evaluations involving observation, noninvasive diagnostic procedures or sampling, or questionnaires as follow-up to a prior study or as components of a concurrent noninterventional study.
  14. Use within 5 days prior to randomization of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 or expected requirement for chronic use of a strong inhibitor or inducer of CYP3A4 during study therapy.
  15. Use within 5 days prior to randomization of drug that is a moderate-to-strong substrate of CYP2C9 (including warfarin, tolbutamide, phenytoin, glimepiride) or expected requirement for chronic use of such drugs during study therapy.
  16. Use within 5 days prior to randomization of a drug known to prolong the QT interval
  17. Ongoing immunosuppressive therapy including systemic or enteric corticosteroids. (Note: At study entry, participants may be using intraarticular, inhaled, or topical corticosteroids. During study therapy, participants may use systemic, enteric, intraarticular, inhaled, or topical corticosteroids as required for intercurrent conditions.)
  18. Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a participant's ability to provide informed consent, adversely affect the participant's ability to cooperate and participate in the study, or compromise the interpretation of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04446377


Contacts
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Contact: Peter Young, PhD 415 860-8370 pyoung@ai-thera.com

Locations
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United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
Principal Investigator: Charles Dela Cruz, MD, Ph.D         
Sponsors and Collaborators
AI Therapeutics, Inc.
Yale University
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Responsible Party: AI Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04446377    
Other Study ID Numbers: LAM-002A-CVD-CLN01
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AI Therapeutics, Inc.:
COVID-19
SARS-CoV-2
Apilimod Dimesylate
LAM-002A
Coronavirus
AI Therapeutics
Additional relevant MeSH terms:
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Disease Progression
Disease Attributes
Pathologic Processes