A Phase Ib Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel)(R) With or Without AP 10-701 for Intestinal Schistosomiasis in Healthy Exposed Adults

NCT03110757 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14-0100HHSN272201300015I
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be conducted as a randomized, controlled, double blind Phase 1b dose-escalating clinical trial in up to 60 healthy adult males and non-pregnant females living in the S. mansoni-endemic area of Americaninhas, Brazil. The primary objective of this trial is to assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel(R) (10mcg, 30mcg, or 100mcg) vaccine with or without AP 10-701 given as three doses administered on Days 1, 57, and 113.

Conditions

Schistosomiasis

Keywords

AP 10-701; healthy adults; Immunogenicity; Phase Ib; Reactogenicity; Safety; Schistosomiasis; Sm-TSP-2/Alhydrogel®

Outcome Measures

Primary Outcomes (13)

• The occurrence of new-onset chronic medical conditions (including AESI)

  From Day 1 to Day 478

• The occurrence of solicited injection site reactogenicity

  From Day 1 to Day 7

• The occurrence of solicited injection site reactogenicity

  From Day 113 to Day 120

• The occurrence of solicited injection site reactogenicity

  From Day 57 to Day 64

• The occurrence of solicited systemic reactogenicity

  From Day 1 to Day 7

• The occurrence of solicited systemic reactogenicity

  From Day 113 to Day 120

• The occurrence of solicited systemic reactogenicity

  From Day 57 to Day 64

• The occurrence of study vaccine-related SAEs

  From Day 1 to Day 478

• The occurrence of vaccine-related clinical safety laboratory adverse events

  Day 113

• The occurrence of vaccine-related clinical safety laboratory adverse events

  Day 120

• The occurrence of vaccine-related clinical safety laboratory adverse events

  Day 57

• The occurrence of vaccine-related clinical safety laboratory adverse events

  Day 64

• The occurrence of vaccine-related clinical safety laboratory adverse events

  Day 8

Secondary Outcomes (6)

• The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA

  Day 15

• The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA

  Day 203

• The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA

  Day 293

• The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA

  Day 478

• The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA

  Day 71

Study Arms (7)

Group A

EXPERIMENTAL

10mcg Sm-TSP-2/Alhydrogel® (n=8)

Biological: Sm-TSP-2/Alhydrogel

Group B

EXPERIMENTAL

10mcg Sm-TSP-2/Alhydrogel®/+ AP 10-701 (n=8)

Biological: GLA-AF; Biological: Sm-TSP-2/Alhydrogel

Group D

EXPERIMENTAL

30mcg Sm-TSP-2/Alhydrogel® (n=8)

Biological: Sm-TSP-2/Alhydrogel

Group E

EXPERIMENTAL

30mcg Sm-TSP-2/Alhydrogel®/+ AP 10-701 (n=8)

Biological: GLA-AF; Biological: Sm-TSP-2/Alhydrogel

Group G

EXPERIMENTAL

100mcg Sm-TSP-2/Alhydrogel® (n=8)

Biological: Sm-TSP-2/Alhydrogel

Group H

EXPERIMENTAL

100mcg Sm-TSP-2/Alhydrogel®/+ AP 10-701 (n=8)

Biological: GLA-AF; Biological: Sm-TSP-2/Alhydrogel

Pooled Active Comparator Group

ACTIVE COMPARATOR

Euvax B Hepatitis B vaccine (n=12)

Biological: Hepatitis B Virus Vaccine (Recombinant)

Interventions

GLA-AF BIOLOGICAL

Previously referred to as Gluco-pyranosylphospho-lipid A aqueous formulation (GLA-AF). It is a toll-like receptor-4 agonist

Group B; Group E; Group H

Hepatitis B Virus Vaccine (Recombinant) BIOLOGICAL

A non-infectious subunit viral vaccine derived from hepatitis B surface antigen (HBsAg) produced in yeast cells.

Pooled Active Comparator Group

Sm-TSP-2/Alhydrogel BIOLOGICAL

Sm-TSP-2/Alhydrogel

Group A; Group B; Group D; Group E; Group G; Group H

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to any study procedures.
• Able to understand and comply with planned study procedures and be available for all study visits.
• Male or non-pregnant female aged 18 to 50, inclusive at the time of enrollment.
• Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and brief physical examination at screening.

You may not qualify if:

• 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 38.0 degrees celsius, (b) pulse 50 to 100 bpm, inclusive, (c) systolic blood pressure 85 to 150 mmHg, inclusive, and (d) diastolic blood pressure 55 to 90 mmHg, inclusive. Pulse rate \<50 is acceptable for 2nd and 3rd vaccinations if the subject is otherwise healthy with documented sinus bradycardia at baseline.
• Laboratory tests (alanine aminotransferase, creatinine, white blood cell count, hemoglobin, and platelets) are all within protocol-defined reference ranges.
• The protocol-defined ranges for laboratory tests include (a) alanine aminotransferase (ALT) of less than 1.25-times the upper reference limit, (b) creatinine less than 1.25 times the upper reference limit (c) white blood cells (WBC) between 3.3 x10\^3/uL and 10.4 x10\^3/uL, inclusive, (d) hemoglobin 11.4 g/dL or greater for females or 12.1 g/dL or greater for males, (e) platelets greater than 130 x10\^3/uL. Laboratory test results for 2nd and 3rd vaccinations may be at Grade 1 if considered unrelated to study product.
• Urinalysis with no greater than trace protein and negative for glucose.
• Female subjects of childbearing potential must agree to practice highly effective contraception for a minimum of 30 days prior to study product exposure and for 30 days after last vaccination.
• Female subjects who are surgically sterile via tubal sterilization, bilateral oophorectomy or hysterectomy or who have been postmenopausal for greater than 1 year are not considered to be of childbearing potential.
• Highly effective methods of contraception are defined as having low failure rates (i.e. less than 1% per year) when used consistently and correctly and may include, but are not limited to, abstinence from intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms or diaphragm with spermicide, intrauterine devices, and licensed hormonal methods.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
• Able to correctly answer all questions on the informed consent comprehension questionnaire.
• Has the intention to become pregnant within 5 months after enrollment in this study.
• Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after their last study vaccination.
• Has an acute illness, including a documented oral temperature of 38.0 degrees celsius or greater, within 72 hours prior to vaccination.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
• Is immunosuppressed as a result of an underlying illness or treatment.

Sponsors & Collaborators

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

Study Sites (1)

Americaninhas Vaccine Center

Novo Oriente, Minas Gerais, Brazil

Location

Related Publications (1)

• Diemert DJ, Correa-Oliveira R, Fraga CG, Talles F, Silva MR, Patel SM, Galbiati S, Kennedy JK, Lundeen JS, Gazzinelli MF, Li G, Hoeweler L, Deye GA, Bottazzi ME, Hotez PJ, El Sahly HM, Keitel WA, Bethony J, Atmar RL. A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. PLoS Negl Trop Dis. 2023 Mar 30;17(3):e0011236. doi: 10.1371/journal.pntd.0011236. eCollection 2023 Mar.

  PMID: 36996185 DERIVED

MeSH Terms

Conditions

Schistosomiasis

Interventions

GLA-AF adjuvant; Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

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

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: April 12, 2017
• Study Start: May 20, 2018
• Primary Completion: November 14, 2019
• Study Completion: November 14, 2019
• Last Updated: February 2, 2021

Record last verified: 2021-01-26

Locations

BR (1)