A Phase III Trial to Evaluate the Safety and Efficacy of Anti-inflammatory Drugs in Addition to Praziquantel in Girls and Women With Female Genital Schistosomiasis (WINGS-4-FGS)
A Phase III, Randomised, Open-Label, Parallel-Group, Controlled Trial to Evaluate the Safety and Efficacy of Anti-inflammatory Drugs (Diclofenac and Prednisolone) in Addition to Praziquantel in Girls and Women (15-49 Years Old) With Female Genital Schistosomiasis
Female Genital Schistosomiasis (FGS) is a neglected complication of Schistosoma haematobium infection affecting an estimated 56 million women and girls globally, with a high burden in sub-Saharan Africa. Up to 75% of infected women develop genital lesions, often without being aware of their condition. FGS causes chronic genital and urinary symptoms, overlaps clinically with sexually transmitted infections, and increases the risk of HIV acquisition by 2-4 times. FGS remains widely underdiagnosed due to limited healthcare provider training, stigma, and lack of affordable diagnostic tools in resource-limited settings. Current control strategies rely on mass drug administration of praziquantel (PZQ) targeting school-aged children and adults in high risk or endemic communities, which neither adequately reaches affected women nor addresses established genital morbidity. PZQ eliminates adult worms but does not reverse chronic inflammation or granulomas caused by trapped eggs, and no clinical guidelines exist for managing FGS-related morbidity. Given these gaps, there is an urgent need to evaluate additional, locally available treatments in combination with praziquantel to reduce inflammation, improve morbidity outcomes, and inform effective clinical management of FGS.
This trial is funded by Global Health EDCTP3 and sponsored by KUHeS, INRB, UFHB, and UHAS. This Phase III, open label, 4x2 factorial superiority randomized controlled trial will take place in multiple schistosomiasis endemic countries in sub-Saharan Africa, among women living with schistosomiasis, testing already registered anti-inflammatory drugs (prednisolone, diclofenac). Each arm shall have at least 100 participants, who shall be followed up at 3-, 6-, and 12-month post first IP administration.
The trial will recruit 800 girls and women of reproductive age (15- 49 years) at 4 sites (Malawi, Ghana, Democratic Republic of Congo, and Cote d'Ivoire), with each site aiming to recruit 200 participants (25 per site per treatment arm).
Přehled studie
Postavení
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Janelisa Professor
- Telefonní číslo: +265884595095
- E-mail: jmusaya@mlw.mw
Studijní místa
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Abidjan, Côte d'ivoire
- Bouafle and Zuenoula
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Kontakt:
- Mamadou Doctor
- Telefonní číslo: +265884595095
- E-mail: mamadou_ouatt@yahoo.fr
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Kimpese, Demokratická republika Konga
- Kimpese
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Kontakt:
- Dieudonne Professor
- Telefonní číslo: +265884595095
- E-mail: mumbadiedonne@yahoo.fr
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Ho, Ghana
- Asuogyaman
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Kontakt:
- Wisdom Professor
- Telefonní číslo: +233244940594
- E-mail: wazanu@uhas.edu.gh
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Mangochi, Malawi
- Mangochi DHO
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Kontakt:
- Jenalisa Professor
- Telefonní číslo: +265884595095
- E-mail: jmusaya@mlw.mw
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Signed written Informed Consent by Participant and assent for minor participants.
- Girls and women aged 15- 49 years.
- Weight ≥ 35kgs (only in the applicable countries due to Diclofenac prescription limitation)
- Girls and women must have had their sexual debut.
- Agreed to have a gynecological exam including colposcopy, provide a cervicovaginal swab and lavage, urine, stool, and a venous sample.
- Confirmed case of FGS: (a) self-reporting symptoms AND (b) parasitological/antigen confirmation of Schistosoma infection (Egg positivity) AND (c) DNA positivity from genital samples AND (d) FGS pathognomonic lesions from colposcopy.
- Acceptance of the requirement to use a barrier form of birth control (e.g. condoms) or other effective contraceptive method effective from Day 1 until Day 57 or documented permanent infertility or postmenopausal status.
Exclusion Criteria:
- Pregnant women.
- Gynecological or any other type of cancer.
- Presence of abnormal physical findings or laboratory values at screening (e.g. severe anaemia) that could interfere with the objectives of the trial or the safety of the subject, in the opinion of the Investigator.
- Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (example, compromise the well-being of the participant), or that could prevent, limit, or confound the protocol specified assessments.
- Treatment with PZQ or drugs with known anti-schistosomal effect within the last 3 months.
- History or presence of gastro-duodenal ulcers or hematemesis, signs, or symptoms of gastritis.
- Contraindication to any of the study drugs, as stated in the approved Reference Safety Information (SmPC).
- Living less than one year in the community.
- Known allergy to the drugs or any of their ingredients used in the trial.
- Current enrolment or past participation in another investigational trial in which an investigational intervention (e.g. drug, vaccine, invasive devise) was administered within 30 days or 5 half-lives (whichever is the longest) before first dose of trial drug (to be adjusted as per country-specific regulation).
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Žádný zásah: Praziquantel 40
Praziquantel 40 given on day 1, day 28 and day 56 |
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Experimentální: Praziquantel 80
Praziquantel 80 given on day 1, day 28 and day 56 |
Praziquantel 80mg (High dose) compared to 40mg SoC |
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Experimentální: Praziquantel 40 plus Prednisolone 5d
Praziquantel 40 given on day 1, day 28 and day 56 plus Prednisolone from day 1 to day 5 |
5 days Prednisolone 20mg given with Praziquantel 40mg |
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Experimentální: Praziquantel 80 plus Prednisolone 5d
Praziquantel 80 given on day 1, day 28 and day 56 plus Prednisolone from day 1 to day 5 |
Prednisolone 20mg from day 1 to day 5 given with Praziquantel 80mg/kg dose on days 1, 28 and 56. |
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Experimentální: Praziquantel 40 plus Diclofenac 5d
Praziquantel 40 given on day 1, day 28 and day 56 plus Diclofenac from day 1 to day 5 |
5 days Diclofenac given with Praziquantel 40mg 15 days Diclofenac given with Praziquantel 40mg |
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Experimentální: Praziquantel 80 plus Diclofenac 5d
Praziquantel 80 given on day 1, day 28 and day 56 plus Diclofenac from day 1 to day 5 |
Diclofenac 75mg from day 1 to day 5 given with Praziquantel 80mg/kg dose on days 1, 28 and 56. |
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Experimentální: Praziquantel 40 plus Diclofenac 15d
Praziquantel 40 given on day 1, day 28 and day 56 plus Diclofenac from day 1 to day 15 |
5 days Diclofenac given with Praziquantel 40mg 15 days Diclofenac given with Praziquantel 40mg |
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Experimentální: Praziquantel 80 plus Diclofenac 15d
Praziquantel 80 given on day 1, day 28 and day 56 plus Diclofenac from day 1 to day 15 |
Diclofenac 75mg from day 1 to day 15 given with Praziquantel 80mg/kg dose on days 1, 28 and 56. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Improvement in pathognomonic sign(s) in the cervix from baseline to month 3.
Časové okno: 3 months
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Improvement in pathognomonic sign(s) in the cervix from baseline to month 3 (binary outcome of improvement vs no improvement) from cervical assessments only using Female Genital Schistosomiasis lesion indicators; grainy sandy patches, homogenous yellow patches and rubbery papules. |
3 months
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Improvement (reduction) in urogenital frequency symptom score from baseline to month 3.
Časové okno: 3 months
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Improvement (reduction) in urogenital (gynaecological) frequency symptom score on a 0-4 scale, calculated as sum total of eight symptom components; lower abdominal pain, dysuria, vulvovaginal itching, abnormal vaginal discharge, menstrual disturbances, intermenstrual bleeding, dyspareunia and bleeding during or after intercourse, from baseline to month 3 (continuous outcome). Higher scores will indicate greater symptom burden. |
3 months
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Effect of anti-inflammatory and Praziquantel dose on overall clinical improvement in women with FGS
Časové okno: 12 months
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Assessing improvement in pathognomonic sign(s) in the cervix by FGS lesion indicators and urogenital (gynaecological) overall symptom score from baseline to months 3 (PZQ dose comparison only), 6 and 12. |
12 months
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Effect of anti-inflammatory and Praziquantel dose on parasitological improvement in women with Female Genital Schistosomiasis.
Časové okno: 12 months
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Assessed by measuring; Antigen (Circulating Anodic Antigen) concentration in urine at day 28, day 56 and month 3, 6, 12, total egg count by urine filtration at days 28 and 56 and months 3, 6, 12, and the absence of schistosome DNA in cervicovaginal swabs at months 3, 6, 12. |
12 months
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Safety and tolerability of anti-inflammatory and Praziquantel treatment in women with Female Genital Schistosomiasis
Časové okno: 12 months
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Assessing the safety and tolerability of trial treatments by occurrence of treatment emergent adverse events (TEAE) in all arms categorized as; non-serious TEAEs up to day 57, serious adverse events (SAEs) up to day 57, TEAE leading to discontinuation of treatment up to day 57, TEAE leading to trial withdrawal up to day 57, Fatal SAE up to month 12, and TEAE reported as related to trial drugs up to month 12. |
12 months
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Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Organické chemikálie
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Karboxylové kyseliny
- Polycyklické sloučeniny
- Těhotenství
- Těhotenství
- Steroidy
- Sloučeniny roztaveného kruhu
- Těhotenství
- Kyseliny, karbocyklické
- Fenylacetáty
- Isochinoliny
- Prednisolon
- Diclofenac
- Praziquantel
Další identifikační čísla studie
- FGS-DPP-01
- 101190584 (Jiné číslo grantu/financování: EDCTP3)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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