Evaluation of IGM-6268 in Healthy Adults and Patients With Mild to Moderate COVID-19

Study Overview
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Brief Summary
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This is a Phase 1, multi-center, randomized, double-blinded, placebo-controlled study to assess the safety, tolerability, and pharmacokinetics (PK) of IGM-6268 administered intranasally and intraorally in healthy volunteers and in outpatients with mild-moderate COVID-19. IGM-6268 or placebo will be administered by intranasal + intraoral spray using a Teleflex Mucosal Atomization Device Nasal™ Intranasal Mucosal Atomization Device once, or once or twice each day for 5 days.

Detailed Description
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IGM-6268 is an engineered Immunoglobulin M (IgM) antibody that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. This humanized pentameric IgM antibody has 10 binding sites to the spike protein and a J-chain to enable the formation of IgM pentamers. IGM-6268 is being developed as a treatment for or prophylaxis of symptoms associated with mild to moderate COVID-19. The primary mechanism of action of IGM-6268 is to block the binding of the SARS-CoV-2 RBD on the spike protein to human angiotensin converting enzyme 2 (hACE2), the cellular receptor for SARS-CoV-2. By blocking this binding, IGM 6268 neutralizes the infectivity of the virus.

Official Title
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A Phase 1 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Intranasal Plus Intraoral IGM-6268 in Healthy Adults and Patients With Mild to Moderate COVID-19

Conditions
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Healthy Volunteers, COVID-19

Intervention / Treatment
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* Drug: IGM-6268
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Healthy Volunteers Inclusion Criteria: Is male or non-pregnant female adult ≥ 18 and ≤ 55 years of age Has a body mass index (BMI) < 35 kg/m2. Is healthy as determined by medical history and physical examination Agrees to use contraception through 3 months after the last dose of IGM-6268 Exclusion Criteria: Receipt of any COVID-19 vaccine during this study and follow-up period Prior positive SARS-CoV2 test Hepatitis B virus (HBV), hepatitis C virus (HCV), or uncontrolled human immunodeficiency virus (HIV) infection Use of any nasally administered drug Mild-Moderate COVID Patients Inclusion Criteria: Is male or non-pregnant female adult ≥ 18 and ≤ 55 years of age Agrees to use contraception through 3 months after the last dose of IGM-6268 Agrees to the collection of blood, urine, saliva, and nasopharyngeal samples, per protocol. Signs and symptoms of mild to moderate COVID-19 but not requiring hospitalization Has a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-authorized antigen or NAAT diagnostic assay during the period of 72 hours prior to enrollment. Exclusion Criteria: Receipt of any COVID-19 vaccine during this study and follow-up period Receipt of remdisivir, antiviral antibody treatment (plasma or Mabs), immosuppressive therapies, or cytokine-targeted anti-inflammatory drugs Concurrent use of drugs not approved for use in COVID-19 patients (e.g., ivermectin, chloroquine/hydroxychloroquine, budesonide). Co-morbidities including but not limited to hypertension, cardiovascular disease, diabetes (Type 1 or 2), chronic kidney disease, or asthma Subject is considered to be in their last few weeks of life prior to this acute illness Cancer within the last 5 years except stable prostate cancer and basal cell carcinoma Hepatitis B virus (HBV), hepatitis C virus (HCV), or uncontrolled human immunodeficiency virus (HIV) infection Influenza or confirmed or suspected pulmonary or systemic bacterial infection Receipt of any COVID-19 vaccine during this study and follow-up period Use of any nasally administered drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects will be randomized to receive intranasal and intraoral administration of IGM-6268 or placebo at the assigned doses. Cohorts will be enrolled sequentially. Cohorts 1-3 and Sentinel will enroll healthy volunteers and Cohorts 4-5 and Ph1b Expansion will enroll mild-moderate COVID-19 patients.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sentinel<br>In the Sentinel Cohort, healthy volunteers will be randomized to receive intranasal and intraoral administration of 1 mg of IGM 6268 or placebo once per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Cohort 1<br>In Cohort 1, healthy volunteers will be randomized to receive intranasal and intraoral administration of 3.75 mg of IGM 6268 or placebo once per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Cohort 2<br>In Cohort 2, healthy volunteers will be randomized to receive intranasal and intraoral administration of 7.5 mg of IGM 6268 or placebo once per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Cohort 3<br>In Cohort 3, healthy volunteers will be randomized to receive intranasal and intraoral administration of 7.5 mg of IGM 6268 or placebo twice per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Cohort 4<br>In Cohort 4, mild-moderate Covid patients will be randomized to receive intranasal and intraoral administration of 7.5 mg of IGM 6268 or placebo once per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Cohort 5<br>In Cohort 5, mild-moderate Covid patients will be randomized to receive one intranasal and intraoral administration of 7.5 mg of IGM 6268 or placebo twice per day for 5 days. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: Ph1b Expansion<br>In the Ph1b expansion cohort, mild-moderate Covid patients will be randomized to receive one intranasal and intraoral administration of 7.5 mg of IGM 6268 or placebo once or twice per day for 5 days. This cohort may be opened per Sponsor's discretion based on initial safety and activity. | Drug: IGM-6268<br>* Active Comparator<br>Drug: Placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety & tolerability of IGM-6268 by assessing the number, severity, and type of adverse events per CTCAE 5.0 |  | Through 60 days following receipt of final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of IGM-6268 in serum |  | Predose through Day 6 (healthy volunteers) or Day 5 (mild-moderate COVID patients) | 
| Incidence of anti-IGM-6268 antibodies in serum |  | Prior to dosing and at Day 28 following receipt of initial dose |