rCSP/AP10-602 [GLA-LSQ] Vaccine Trial

NCT03589794 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13-0088HHSN272201300022I
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602 \[Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)\] adjuvant. 59 healthy adult, malaria naive volunteers aged 18 to 45 will receive vaccination with or without adjuvant (10 of those volunteers will receive rCSP alone) in five dose escalating groups. Each group will receive 3 vaccination doses total, with intramuscular (IM) injections on days 1, 29, and 85. A sixth group of 6 volunteers will receive no vaccinations and will participate as a control in a Controlled Human Malaria Infection (CHMI) challenge with two of the vaccinated groups. The study will be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. The patient participation duration is expected to be up to 886 days (up to 117 days for nonvaccination group). This study will test two hypotheses: (1) the rCSP/AP 10-602 \[GLA-LSQ\] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 \[GLA-LSQ\] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 \[GLA-LSQ\] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years.

Conditions

Plasmodium Falciparum Infection

Keywords

AP 10-602 [GLA-LSQ]; Challenge; Healthy adults; Malaria; P. falciparum; rCSP; Vaccine

Outcome Measures

Primary Outcomes (7)

• Number of subjects reporting Adverse Events of Special Interest (AESIs)

  According to the Medical Dictionary for Regulatory Activities (MedDRA) classification

  Day 1 to Day 450

• Number of subjects reporting serious adverse events (SAEs)

  According to the Medical Dictionary for Regulatory Activities (MedDRA) classification

  Day 1 to Day 450

• Number of subjects reporting serious adverse events (SAEs) considered related to vaccination

  According to the Medical Dictionary for Regulatory Activities (MedDRA) classification

  Day 1 through Day 113

• Number of subjects reporting severe (Grade 3) laboratory Adverse Events (AE) considered related to vaccination

  According to the Medical Dictionary for Regulatory Activities (MedDRA) classification

  Day 1 through Day 92

• Number of subjects reporting solicited local reactions

  Day 1 through Day 92

• Number of subjects reporting solicited systemic reactions

  Day 1 through Day 92

• Number of subjects reporting unsolicited adverse events (AEs) considered related to vaccination and that are severe (Grade 3)

  According to the Medical Dictionary for Regulatory Activities (MedDRA) classification

  Day 1 through Day 113

Secondary Outcomes (3)

• Antibody titer against the malaria circumsporozoite antigen

  Day 1 through Day 574

• Presence of P. falciparum asexual parasitemia following experimental malaria challenge

  Day 118 to Day 141

• Time to P. falciparum asexual parasitemia following experimental malaria challenge

  Day 118 to Day 141

Study Arms (7)

Group 1

EXPERIMENTAL

10 subjects receive 10 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85.

Other: AP10-602; Biological: rCSP

Group 2

EXPERIMENTAL

10 subjects receive 30 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85.

Other: AP10-602; Biological: rCSP

Group 3

EXPERIMENTAL

10 subjects receive 30 mcg rCSP intramuscularly (IM) on days 1, 29 and 85.

Biological: rCSP

Group 4

EXPERIMENTAL

9 subjects receive 60 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113.

Other: AP10-602; Other: Malaria challenge; Biological: rCSP

Group 4B

EXPERIMENTAL

10 subjects receive 60 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113.

Other: AP10-602; Other: Malaria challenge; Biological: rCSP

Group 5

EXPERIMENTAL

10 subjects receive 10 mcg or 30 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85 if immunogenicity analysis conducted 28 days post-2nd dose in Groups 1, 2, and 3 show promise (at least fourfold increase in geometric mean anti-CSP antibody or geometric mean anti-CSP titer of 20). Otherwise, subjects will receive 60 mcg rCSP + AP 10-602 \[GLA-LSQ\] (5 mcg GLA - 2 mcg LSQ). Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113.

Other: AP10-602; Other: Malaria challenge; Biological: rCSP

Group 6

OTHER

6 subjects receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain.

Other: Malaria challenge

Interventions

AP10-602 OTHER

Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).

Group 1; Group 2; Group 4; Group 4B; Group 5

Malaria challenge OTHER

Exposure to mosquitoes infected with P. falciparum.

Group 4; Group 4B; Group 5; Group 6

rCSP BIOLOGICAL

The rCSP malaria vaccine is a recombinant full-length P. falciparum circumsporozoite protein comprised of an amino terminus that binds heparin-sulfate proteoglycans, a four-amino-acid repeat region and a carboxy-terminus that contains a thrombospondin-like Type I region domain.

Group 1; Group 2; Group 3; Group 4; Group 4B; Group 5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18 and 45 years, inclusive
• Able and willing to participate for the duration of the study
• Able and willing to provide written (not proxy) informed consent
• Provides informed consent and correctly answers \> / = 70 percent on the post consent quiz before any study procedures and is available for all study visits
• Females of childbearing potential and males must agree to practice highly effective contraception\*
• \*Contraception must be practiced from 30 days before the time of enrollment until at least 30 days following the third vaccine dose for groups 1, 2 and 3, and the malaria challenge event for groups 4, 4B, 5 and 6 (such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), licensed intrauterine devices (IUDs), intravaginal or intra/transdermal or oral hormonal methods initiated at least 30 days before inoculation or challenge, documented surgical sterilization via tubal ligation the essure procedure or hysterectomy, abstinence or a vasectomized partner). The contraceptive method should remain unchanged throughout the study participation
• Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature); medical history; laboratory values\* that do not meet toxicity grading criteria, except when Grade 1 and clinically insignificant; and a physical examination
• \*Laboratory values include: hemoglobin, white blood cell count, platelet count, glucose (random), serum alanine aminotransferase (ALT), serum creatinine, urine protein and urine blood
• Agree not to travel to a malaria endemic region during the entire course of the trial
• Willing to avoid non-study related blood donation for the duration of participation in the study or until at least 1 year after receiving the last investigational vaccine, whichever is longer
• Able to understand and comply with planned study procedures including daily outpatient follow-up visits beginning 5 days after malaria challenge (groups 4, 4B, 5 and 6 only)
• Willing to avoid non-study related blood donation for 3 years following P. falciparum challenge (groups 4, 4B, 5 and 6 only)

You may not qualify if:

• Any history of malaria infection, or travel to a malaria endemic region within 6 months before first vaccination
• History of long-term residence (\> / = 5 years) in an area known to have significant transmission of P. falciparum
• Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg)
• Positive sickle cell screening test or known hemoglobinopathy (groups 4, 4B, 5 and 6 only)
• Current or recent (within the last four weeks) treatment with parenteral or oral corticosteroids (intranasal or inhaled steroids are acceptable), or other immunosuppressive agents, or chemotherapy
• History of splenectomy
• Participants who have a clinically significant (as determined by the PI or designee) baseline Grade 1 or greater toxicity, or any Grade 2 or greater toxicity (regardless of clinical significance) by the toxicity table, except hematuria \> 1+ detected during menses for females\*
• \* For females who are menstruating, urinalysis frequently tests positive for blood and is not an indicator of poor health status or increased risk.
• Vaccination with a live vaccine within the past 30 days or with a nonreplicating, inactivated, or subunit vaccine within the last 14 days
• Known hypersensitivity to components of the vaccine for groups 1, 2, 3, 4, 4B and 5; or to the adjuvant for groups 1, 2, 4, 4B and 5
• History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, nervous system, or other metabolic or autoimmune/inflammatory conditions
• History of anaphylaxis or severe hypersensitivity reaction
• History of Guillain-Barre syndrome or severe adverse reaction to any vaccination
• Severe asthma, as defined by an emergency room visit or hospitalization within the last 12 months
• Pregnant or breastfeeding women or women who plan to become pregnant before day 115 in groups 1, 2 and 3; or before 30 days post-malaria challenge in groups 4, 4B, 5 and 6

Sponsors & Collaborators

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

Study Sites (1)

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Related Publications (2)

• Friedman-Klabanoff DJ, Berry AA, Travassos MA, Shriver M, Cox C, Butts J, Lundeen JS, Strauss KA, Joshi S, Shrestha B, Mo AX, Nomicos EYH, Deye GA, Regules JA, Bergmann-Leitner ES, Pasetti MF, Laurens MB. Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge. J Infect Dis. 2024 Jun 14;229(6):1883-1893. doi: 10.1093/infdis/jiae062.

  PMID: 38330357 DERIVED

• Friedman-Klabanoff DJ, Berry AA, Travassos MA, Cox C, Zhou Y, Mo AX, Nomicos EYH, Deye GA, Pasetti MF, Laurens MB. Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing. Vaccine. 2021 Feb 22;39(8):1195-1200. doi: 10.1016/j.vaccine.2020.12.023. Epub 2021 Jan 22.

  PMID: 33494963 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 18, 2018
• Study Start: December 21, 2018
• Primary Completion: July 5, 2022
• Study Completion: July 5, 2022
• Last Updated: July 10, 2023

Record last verified: 2021-04-19

Locations

US (1)