Safety, Tolerability, and Immunogenicity Study of Sm-p80 + GLA-SE (SchistoShield(R)) Vaccine in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 1, open-label, dose-escalation clinical trial to evaluate the safety, reactogenicity, and immunogenicity of the Sm-p80+GLA-SE vaccine candidate in healthy adults between 18 and 55 years of age. Forty-five subjects will receive a series of three intramuscular injections 28 days apart with dose based on group. Five treatment groups, each including nine subjects, will receive three intramuscular (IM) injections of 0.5 mL of the designated study product on either Days 1, 29, and 57 or on Days 1, 29, and 180 (Table 1). Group A (unadjuvanted comparator) will receive 100 micrograms Sm-p80 alone on Days 1, 29, and 57, Group B (low dose standard schedule) will receive 10 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57, Group C (mid dose delayed booster) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 180, Group D (mid dose standard schedule) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29, and 57, and Group E (high dose standard schedule) will receive 100 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57. Study duration is approximately 20 months and will be conducted at one site in the US. Participant duration for subjects is 15 months. The primary objective is to assess the safety and reactogenicity following receipt of three doses of 1) 100 micrograms Sm- p80 (unadjuvanted), 2) 10 micrograms Sm-p80 + 5 micrograms GLA-SE, 3) 30 micrograms Sm-p80 + 5 micrograms GLA- SE, and 4) 100 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57 and 5) 30 micrograms Sm-p80 + 5 micrograms GLA- SE administered on Days 1, 29, and 180.

Detailed Description
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This is a Phase 1, open-label, dose-escalation clinical trial to evaluate the safety, reactogenicity, and immunogenicity of the Sm-p80+GLA-SE vaccine candidate in healthy adults between 18 and 55 years of age. Forty-five subjects will receive a series of three intramuscular injections 28 days apart with dose based on group. Five treatment groups, each including nine subjects, will receive three intramuscular (IM) injections of 0.5 mL of the designated study product on either Days 1, 29, and 57 or on Days 1, 29, and 180 (Table 1). Group A (unadjuvanted comparator) will receive 100 micrograms Sm-p80 alone on Days 1, 29, and 57, Group B (low dose standard schedule) will receive 10 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57, Group C (mid dose delayed booster) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 180, Group D (mid dose standard schedule) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29, and 57, and Group E (high dose standard schedule) will receive 100 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57. Study duration is approximately 20 months and will be conducted at one site in the US. Participant duration for subjects is 15 months. The primary objective is to assess the safety and reactogenicity following receipt of three doses of 1) 100 micrograms Sm- p80 (unadjuvanted), 2) 10 micrograms Sm-p80 + 5 micrograms GLA-SE, 3) 30 micrograms Sm-p80 + 5 micrograms GLA- SE, and 4) 100 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57 and 5) 30 micrograms Sm-p80 + 5 micrograms GLA- SE administered on Days 1, 29, and 180. The secondary objectives are to assess anti- Sm-p80 Immunoglobulin G (IgG) antibody responses for all subjects from samples collected at specified time points.

Official Title
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A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of the Sm-p80 + GLA-SE (SchistoShield(R)) Vaccine in Healthy Adults

Conditions
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Schistosomiasis

Intervention / Treatment
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* Biological: Sm-p80 + GLA-SE
* Biological: Sm-p80


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female 18 through 55 years of age, inclusive, at the time of consent. Able and willing to participate for the duration of the study and able to understand and comply with planned study procedures. Able and willing to provide written (not proxy) informed consent. Is in good health, as judged by the investigator, and determined by medical history and physical examination*. *Existing medical diagnoses or conditions (except those in the Subject Exclusion Criteria) must be deemed as stable. A stable medical condition is defined as no change in prescription medication, dose, or frequency of medication in the last three months (90 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last six months (180 days). Any change due to change of health care provider, insurance company, or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site PI or appropriate sub-investigator, will not be considered a violation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of solicited events and immunogenicity. Topical, nasal, and inhaled medications (with the exception of some uses of corticosteroids as outlined in the Subject Exclusion Criteria), vitamins, and contraceptives are permitted. Women of childbearing potential* must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study product injection. *Not sterilized via bilateral tubal ligation, bilateral oophorectomy, or hysterectomy, or, if menopausal, still menstruating or < 1 year of the last menses Women of childbearing potential must have used an acceptable form of contraception* in the 30 days prior to their first study product injection. *Acceptable single forms of contraception include abstinence from sexual activity that could lead to pregnancy, monogamous relationship with vasectomized partner who has been vasectomized for six months or more prior to enrollment, successful Essure placement (permanent, non-surgical, non-hormonal sterilization), intrauterine devices, and hormonal methods, including the birth control patch, shot (Depo-Provera), pills, the vaginal ring (NuvaRing), and the contraceptive implant (Nexplanon). Acceptable barrier methods include diaphragm or cervical cap with spermicide and the contraceptive sponge. Women of childbearing potential must agree to continue use of an acceptable form of contraception through 30 days after their last study product injection. Weight >/= 50 kg and body mass index (BMI) < 35.0 kg/m2 Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.* *The normal protocol-defined ranges for vital signs include (a) oral temperature less than 38 degrees C (100.4 degrees F), (b) pulse no greater than 100 bpm, (c) systolic blood pressure 85 to 150 mmHg, inclusive, and (d) diastolic BP </= 100 mmHg. Screening clinical lab values are all within normal protocol-defined reference ranges. The normal protocol-defined ranges for laboratory tests include (a) ALT of < 47 IU/L, (b) creatinine less than or equal to the laboratory upper limit of normal, (c) WBC >/=3.80 x10^3/UL and </=13.00 x10^3/UL, (d) hemoglobin 11.5 g/dL or greater for females or 12.6 g/dL or greater for males, (e) platelets between 131 x10^3/UL and 415 x10^3/UL, inclusive. Exclusion Criteria: Has had known schistosomiasis infection or has traveled to an endemic area for schistosomiasis infection and, during that travel, was potentially exposed to a Schistosoma species. Has been treated for schistosomiasis. Has previous exposure to schistosome vaccines or experimental products containing GLA-SE. Female subjects who are breastfeeding a child ,or who plan to breastfeed a child from the first study product injection through 30 days after the last study product injection. Asthma, other than mild, well-controlled asthma* *Cold or exercise-induced asthma controlled with inhaled medications other than inhaled corticosteroids is permissible. Subjects should be excluded if they require daily bronchodilator use, or have had an asthma exacerbation requiring oral/parenteral steroid use or have used theophylline or inhaled corticosteroids in the past year Known atherosclerotic cardiovascular disease or history of myocardial infarction, pericarditis, or myocarditis. Diabetes mellitus History of a psychiatric condition that may make study compliance difficult, such as schizophrenia, or poorly controlled bipolar disorder** **Includes persons with psychoses or history of suicide attempt or gesture in the 3 years before study entry or an ongoing risk for suicide. Chronic or active neurologic condition (including seizures*** and migraine headaches****). ***Seizure within the past 5 years ****Four or more migraine headaches in the past 12 months that interfered with normal daily activity or any migraine headache in the past 5 years that required emergency or inpatient medical care. Autoimmune disease****** ******autoimmune hypothyroidism with or without replacement therapy, and vitiligo or mild eczema or psoriasis not requiring chronic therapy, are permissible Known or suspected congenital or acquired immunodeficiency including anatomic or functional asplenia******* or immunosuppression as a result of underlying illness or treatment. *******Any splenectomy is exclusionary. Use of alcohol or drugs that, in the opinion of the investigator, may interfere with ability to comply with the protocol or increase risk to subject's health during the study period. Active neoplastic disease******** ********Subjects with a history of malignancy may be included if treated by surgical excision, or by chemotherapy or radiation therapy and has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure (not less than 36 months). Cervical neoplasia under surveillance and non-melanoma skin cancer are not exclusionary. Chronic topical or systemic corticosteroid use********* *********Corticosteroid nasal sprays for allergic rhinitis are permissible. Persons using a topical corticosteroid for a limited duration for mild uncomplicated dermatitis such as poison ivy or contact dermatitis prior to enrollment may be enrolled the day after their therapy is completed. Oral or parenteral (intravenous, IM, subcutaneous) corticosteroids given for non-chronic conditions not expected to recur are permissible if, within the year prior to enrollment, the longest course of therapy was no more than 14 days and no oral or parenteral corticosteroids were given within 30 days prior to enrollment. Intraarticular, bursal, tendon, or epidural injections of corticosteroids are permissible if the most recent injection was at least 30 days prior to enrollment. Topical or systemic corticosteroid use for study related AEs is not exclusionary. Known contraindication to repeated phlebotomy********** **********Such as minimal venous access or recent history of anemia Receipt or planned receipt of inactivated vaccine or allergy desensitization injection within 14 days before or after a study product injection. Receipt or planned receipt of live attenuated vaccine within 28 days before or after a study product injection. Receipt of blood products or immunoglobulin within six months prior to, or donation of a unit of blood within two months prior to, the first study product injection. Receipt of any experimental agent*********** within 30 days prior to screening or planned receipt prior to the last study visit-**. ***********Vaccine, drug, biologic, device, blood product, or medication. **Receipt of experimental COVID-19 related products are not necessarily exclusionary and will be evaluated on a case-by-case basis. Plan to undergo surgery (elective or otherwise) within six months after study enrollment. Plans to enroll in another interventional clinical trial************ at any time during the study period. ************Includes trials evaluating interventions such as a drug, biologic, or device. Positive confirmatory test for HIV infection. Positive serologic test for hepatitis B surface antigen (HBsAg). Positive confirmatory test for hepatitis C virus (HCV) infection. Acute febrile illness (oral temperature = 38°C) or other acute illness within three days prior to study product injection.************* *************Note for afebrile, acute illness only: If a subject is afebrile, his/her acute illness is nearly resolved with only minor residual symptoms remaining, and, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol, the subject may receive study product injection without further approval from the DMID Medical Officer. Not willing to avoid donating blood during the study. Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

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: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>0.5 mL of 100 micrograms of Sm-p80 administered intramuscularly on Days 1, 29, and 57. N=9 | Biological: Sm-p80<br>* The Sm-p80 protein is formulated and lyophilized to yield the vaccine antigen, Sm-p80 for Injection.<br>|
| Experimental: B<br>0.5 mL of 10 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57. N=9 | Biological: Sm-p80 + GLA-SE<br>* Combination vaccine containing Sm-p80 antigen and GLA-SE adjuvant.<br>|
| Experimental: C<br>0.5mL of 30 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 180. N=9. | Biological: Sm-p80 + GLA-SE<br>* Combination vaccine containing Sm-p80 antigen and GLA-SE adjuvant.<br>|
| Experimental: D<br>0.5mL of 30 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57. N=9. | Biological: Sm-p80 + GLA-SE<br>* Combination vaccine containing Sm-p80 antigen and GLA-SE adjuvant.<br>|
| Experimental: E<br>0.5mL of 100 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29 and 57. N=9. | Biological: Sm-p80 + GLA-SE<br>* Combination vaccine containing Sm-p80 antigen and GLA-SE adjuvant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of all unsolicited adverse events (AEs), regardless of the assessment of seriousness or relatedness. |  | Day 1 through Day 208 | 
| Occurrence of clinical safety laboratory Adverse Events (AEs) |  | Day 1 through Day 208 | 
| Occurrence of serious adverse events (SAEs), adverse events of special interests (AESIs), medically attended adverse events (MAAEs), and new onset chronic medical conditions (NOCMCs). |  | Day 1 through Day 545 | 
| Occurrence of solicited injection site and systemic reactogenicity events. |  | Day 1 through Day 187 | 
| Occurrence of study vaccine-related serious adverse events (SAEs). |  | Day 1 through Day 545 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titers of serum Sm-p80 IgG antibodies |  | Day 7 through Day 304 | 
| Sm-p80 IgG antibodies, number of subjects achieving seroconversion. | Defined as a fourfold rise from baseline | Day 28 through Day 208 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Dose-Escalation, Immunigenicity, Open-label, Reactogenicity, Schistosomiasis, Vaccine