Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis

NCT02858817 | Completed Phase 1

• 1 other identifier: MALACHITE
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI. A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl). Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P. Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P. Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is \<75%, volunteers will receive the same sequence as in Group A (NF54-7G8).

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs)

  from time of first administration of A/P until the last follow up visit, 414 days after first administration

Secondary Outcomes (2)

• Occurrence of any related AE

  from time of first administration of A/P until the last follow up visit, 414 days after first administration

• Proportion of protected volunteers

  From time of PfSPZ challenge administration until 28 days after PfSPZ challenge

Other Outcomes (2)

• Time-to-parasitemia in volunteers who receive immunization using PfSPZ Challenge or placebo under A/P chemoprophylaxis and become parasitemic within 28 days following CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8).

  Until 28 days after challenge

• Time-to-parasitemia in placebo recipients following 2nd versus 1st CHMI (carry-over effect).

  Until 28 days after challenge

Study Arms (3)

51,200 PfSPZ

EXPERIMENTAL

Three injections of 51,200 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals

Drug: atovaquone/proguanil 250mg/100mg (A/P); Biological: PfSPZ Challenge (NF54)

150,000 PfSPZ

EXPERIMENTAL

Three injections of 150,000 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals

Drug: atovaquone/proguanil 250mg/100mg (A/P); Biological: PfSPZ Challenge (NF54)

Placebo

PLACEBO COMPARATOR

Three injections of NaCl 0,9% solution under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals

Drug: atovaquone/proguanil 250mg/100mg (A/P); Other: NaCl 0,9%

Interventions

atovaquone/proguanil 250mg/100mg (A/P) DRUG

Combination drug for chemo-prophylaxis or treatment of malaria

Also known as: Malarone

150,000 PfSPZ; 51,200 PfSPZ; Placebo

PfSPZ Challenge (NF54) BIOLOGICAL

cryo-preserved Plasmodium falciparum sporozoites injected by venous inoculation

150,000 PfSPZ; 51,200 PfSPZ

NaCl 0,9% OTHER

0.9% NaCl solution for injection

Also known as: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy adults aged 18 to 45 years.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner if required.
• Residence in Tübingen or surroundings for the period of the trial.
• Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year).
• Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (currently four years in Germany).
• Provision of written informed consent to receive PfSPZ Challenge for immunization and subsequently for CHMI.
• Reachable (24/7) by mobile phone during the immunization and CHMI period.
• Willingness to take A/P during immunization and a curative antimalarial regimen following CHMI.
• Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required.
• Answer all questions on the informed consent quiz correctly.
• A body mass index 18-35.

You may not qualify if:

• History of P.falciparum malaria.
• Planned travel to malaria endemic areas during the study period.
• Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,erythromycin, fluoroquinolones, or azithromycin).
• Receipt of an investigational product in the 90 days preceding enrollment, or planned receipt during the study period.
• HIV infection.
• Any confirmed or suspected immunosuppressive or immunodeficient state (e.g. repeated and/or unusual infections),history of infection caused by opportunistic organisms any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia, asplenia and/or chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)).
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• Known (or signs consistent with) sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency.
• Pregnancy, lactation or intention to become pregnant during the study.
• Contraindications to the use of the following antimalarial medications: A/P, artemether-lumefantrine
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of serious psychiatric condition that may affect participation in the study
• Any other serious chronic illness requiring hospital specialist supervision.
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%.
• Suspected or known injected drug abuse in the 5 years preceding enrollment.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Sanaria Inc.: collaborator

MeSH Terms

Conditions

Malaria

Interventions

Atovaquone; Proguanil; atovaquone, proguanil drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Naphthoquinones; Quinones; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Peter G Kremsner, Prof

  University Hospital Tübingen, Tübingen, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 8, 2016
• Study Start: November 28, 2016
• Primary Completion: November 16, 2017
• Study Completion: November 16, 2017
• Last Updated: July 15, 2019

Record last verified: 2018-02