Phase 1 N=22 Randomized Quadruple-blind Prevention

DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria

Plasmodium Falciparum, Malaria

Bottom Line

View on ClinicalTrials.gov: NCT02450578 ↗

Enrolled (actual)

Serious AEs

4.8%

Results posted

Dec 2020

Primary outcome: Primary: Infection Rate — 5; 6; 3; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: DSM265 400mg (Drug); Placebo to DSM265 400 mg (Drug); Plasmodium falciparum sporozoite challenge (Biological); Malarone (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Medicines for Malaria Venture
Primary completion: Apr 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Infection Rate	5; 6; 3; 0; 0; 0	—
PRIMARY Pre-patent Period	28.0; 28.0; 20.6; 11.7	—
SECONDARY Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265	5; 6	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone	5	—
SECONDARY Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum	3; 5; 5; 4	—
SECONDARY DSM265 Pharmacokinetics Profile - T Max	2.02; 8.48; 2.00; 8.48	—
SECONDARY DSM265 Pharmacokinetics Profile - T 1/2	132; 113; 134; 116	—
SECONDARY DSM265 Pharmacokinetics Profile - C Max	6860; 6990; 13300; 11200	—
SECONDARY DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h	979000; 906000; 1870000; 1540000; 582000; 568000	—
SECONDARY DSM265 Pharmacokinetics Profile - CL/F	409; 441; 214; 260	—
SECONDARY DSM265 Pharmacokinetics Profile - Vz/F	77900; 71700; 41400; 43600	—
SECONDARY DSM450 Pharmacokinetics Profile - T Max	169; 216; 169; 169	—
SECONDARY DSM450 Pharmacokinetics Profile - Cmax	545; 714; 999; 1170	—
SECONDARY DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h	185000; 225000; 326000; 367000; 63800; 85300	—
SECONDARY The Pharmacokinetic-pharmacodynamic Profile of Pre-administration of DSM265 on Clearance of Plasmodium Falciparum Parasites After Administration of the Sporozoite Challenge	—	—
SECONDARY Recrudescence of Parasite Kinetics Following DSM265 Administration.	—	—

Summary

Study to evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and validated Human Challenge model using direct venous inoculation of aseptic, purified, cryopreserved, vialed Plasmodium falciparum sporozoites.

Eligibility Criteria

Inclusion Criteria

Good health based on medical history and physical examination- Body mass index >18 and 450msec)
Clinically significant abnormalities in electrocardiogram at screening: pathologic Q wave, prolonged QT interval, and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block (type 2 or type 3)
In moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk
Positive family history in relatives <50 years for cardiac disease
History of psoriasis or porphyria, which may be exacerbated by chloroquine
History of splenectomy
Sickle cell anaemia or other red blood cell disorders
History of allergy or contra-indications to or having contraindications to the use of chloroquine phosphate, atovaquone-proguanil (cohort 1B), artemether or lumefantrine
Use of any prescription drugs (except contraception), herbal supplements or over-the-counter medication in 4 weeks before dosing or 5x half-lives, whichever is longer
Use or anticipated use of medications known to cause drug reactions with rescue medications or Malarone, such as cimetidine, metoclopramide, antacids and taken at any point during the study period.
Intake of grapefruit, grapefruit juice, Seville orange or other products containing these ingredients within 7 days of the first drug administration
Use of chronic immunosuppressive drugs, or other immune modifying drugs within 6 months of enrolment (inhaled and topical corticosteroids and oral anti-histaminic are allowed) and/or during the study period
Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin ) and/or during the study period
Use of immunoglobulins or blood products in 3 months prior to enrolment
Suspected/known injecting drug abuse in 5 years preceding enrolment
Current smoking more than 10 cigarettes or equivalent per day
Plan for major surgery between enrolment and follow up

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Data sourced from ClinicalTrials.gov (NCT02450578). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.