Smallpox

Summary

Smallpox (MONDO:0004651) is a disease and 58 clinical trials. Top therapeutic interventions include tecovirimat, brincidofovir, and calcium. A subtype of primary viral infectious disease — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Clinical trials: 58

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	smallpox
Mondo ID	MONDO:0004651
MeSH	D012899
DOID	DOID:8736
ICD-10-CM	B03
ICD-11	2054716425
NCIT	C35027
SNOMED CT	67924001
UMLS	C0037354
MedGen	20785
Is cancer (heuristic)	no

Also known as: ordinary smallpox · Variola · Variola virus caused disease or disorder · Variola virus disease or disorder · Variola virus infectious disease

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › viral infectious disease › primary viral infectious disease › smallpox

Related subtypes (31): plantar wart, monkeypox, rubella, human papilloma virus infection, Rotavirus infection, Arenaviridae infectious disease, Astroviridae infectious disease, Caliciviridae infectious disease, cowpox, Flaviviridae infectious disease, Hepadnaviridae infectious disease, Herpesviridae infectious disease, influenza, Mononegavirales infectious disease, Nidovirales infectious disease, phlebotomus fever, Picornaviridae infectious disease, polyomavirus infectious disease, Togaviridae infectious disease, viral encephalitis, viral hepatitis, viral pneumonia, viral exanthem, deltaretrovirus infections, Bunyaviridae infectious disease, viral sexually transmitted disease, lentivirus infection, viral myocarditis, viral pericarditis, adenoviridae infectious disease, aleutian mink disease, human

Subtypes (2): variola major infectious disease, variola minor infection

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated or in trials for this disease

3 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Brincidofovir	Approved (phase 4)
Tecovirimat	Approved (phase 4)
Vaccinia Virus, Live Modified	Approved (phase 4)

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Smallpox Vaccine	Phase 3

Clinical trials & evidence

Clinical trials

Clinical trials: 58.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	20
PHASE1	15
Not specified	7
PHASE3	6
PHASE1/PHASE2	6
PHASE4	2
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04392739	PHASE4	COMPLETED	Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG
NCT04485039	PHASE4	COMPLETED	Drug-drug Interaction Study of TPOXX When Co-administered With Phosphate Binders
NCT00607243	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of CJ-50300 in Healthy Volunteers
NCT01056770	PHASE3	COMPLETED	Safety and Efficacy of CJ Smallpox Vaccine in Healthy Volunteers
NCT01144637	PHASE3	COMPLETED	A Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects
NCT01317238	PHASE3	COMPLETED	Safety and Efficacy of CJ Smallpox Vaccine in Previously Vaccinated Healthy Volunteers
NCT02474589	PHASE3	COMPLETED	A Trial to Assess the Safety, Tolerability, and Pharmacokinetics of the Anti-Orthopoxvirus Compound Tecovirimat
NCT03699124	PHASE3	COMPLETED	Freeze-Dried MVA-BN® Lot Consistency Smallpox Trial
NCT04971109	PHASE3	COMPLETED	Safety, Tolerability and Pharmacokinetics of TPOXX When Administered Orally for 28 Days
NCT05846243	PHASE2/PHASE3	COMPLETED	Study on Immunogenicity, Reactogenicity and Safety of the VACΔ6 Vaccine in Volunteers Aged 18-60 Years
NCT04957485	PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Immunogenicity of TPOXX® When Administered Orally for 28 Days With JYNNEOS
NCT07379580	PHASE2	RECRUITING	A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa
NCT00026611	PHASE2	COMPLETED	A Study of Dryvax Vaccine Against Smallpox in Previously Unvaccinated Adults
NCT00032708	PHASE2	COMPLETED	Dryvax Dilution-Prev Vacc Adults
NCT00038987	PHASE1/PHASE2	COMPLETED	Vaccinia Virus Vaccine (APSV) in Vaccinia- Naive Subjects: PILOT
NCT00050505	PHASE2	COMPLETED	Expanded Dryvax Dilution Study in Previously Vaccinated Adults
NCT00050518	PHASE2	COMPLETED	APSV in Vaccinia Naive Adults
NCT00053482	PHASE2	COMPLETED	Dose Study of ACAM2000 Smallpox Vaccine in Previously Vaccinated Adults
NCT00053495	PHASE2	COMPLETED	Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination
NCT00053508	PHASE2	TERMINATED	Dose Safety, Tolerability, and Immunogenicity of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination
NCT00063856	PHASE1/PHASE2	COMPLETED	Dressing Preparations for Smallpox
NCT00103584	PHASE1/PHASE2	UNKNOWN	Safety and Immunogenicity Study of LC16m8, a Modified Smallpox Vaccine, in Healthy, Previously Unvaccinated Volunteers
NCT00133575	PHASE1/PHASE2	COMPLETED	ACAM 3000 MVA at Harvard Medical School
NCT00189956	PHASE2	COMPLETED	Dose-finding Study to Evaluate Immunogenicity of Three Different Dose Levels of the IMVAMUNE (MVA-BN) Smallpox Vaccine.
NCT00258947	PHASE2	COMPLETED	Evaluation of Take and Safety of a Smallpox Vaccine in Healthy Young Adults
NCT00316524	PHASE2	COMPLETED	A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects
NCT00437021	PHASE1/PHASE2	COMPLETED	MVA Post-Event: Administration Timing and Boost Study
NCT00466245	PHASE2	COMPLETED	Phase 2 Study of Safety, Tolerability, and Immunogenicity of Three Dose Levels of ACAM3000 Smallpox Vaccine
NCT00686582	PHASE2	COMPLETED	An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees
NCT00857493	PHASE2	COMPLETED	A Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-experienced Subjects
NCT00879762	PHASE2	COMPLETED	High Dose IMVAMUNE® in Vaccinia-Naive Individuals
NCT00914732	PHASE2	COMPLETED	Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid IMVAMUNE® (1x10^8 TCID50) Administered Subcutaneously and a Lower Dose Liquid IMVAMUNE® (2x10^7 TCID50) Administered Intradermally
NCT01668537	PHASE2	COMPLETED	A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
NCT01827371	PHASE2	COMPLETED	Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®
NCT02038881	PHASE2	COMPLETED	Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine in Immunocompromised Subjects With HIV Infection
NCT05995275	PHASE1/PHASE2	COMPLETED	A Study to Investigate The Safety, Tolerability, And Immune Response of a Range of Doses of mRNA-1769 Compared With Placebo in Healthy Participants From ≥18 Years of Age to <50 Years of Age
NCT07377175	PHASE1	RECRUITING	Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BSY001 After Single/Multiple Doses.
NCT00042094	PHASE1	COMPLETED	Study of Reactogenicity, Safety, Immunogenicity, and Pock Lesion Formation of a Cell-Cultured Smallpox Vaccine Compared to Dryvax®
NCT00068198	PHASE1	COMPLETED	Human Immune Responses Smallpox
NCT00079820	PHASE1	COMPLETED	Safety, Tolerability, and Immune Response of ACAM3000 Modified Vaccinia Ankara (MVA) Smallpox Vaccine in Adults

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TECOVIRIMAT	4	6
BRINCIDOFOVIR	4	1
CALCIUM	4	1
SMALLPOX VACCINE	3	4
HILTONOL	2	1
CHEMBL485653	0	4
CHEMBL5072826	0	1