HYPATIA: A prospective randomised controlled trial of HYdroxychloroquine to improve Pregnancy outcome in women with AnTIphospholipid Antibodies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Immune System Diseases [C20], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

27 Jun 2023 → ongoing

Decision date (initial)

2023-05-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504661-23-00

EudraCT number

2016-002256-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To study the effect of HCQ on pregnancy outcome in women with antiphospholipid antibodies.

Secondary objectives 1

1. To collect blood samples for pharmacokinetic and biomarkers studies

Conditions and MedDRA coding

Antiphospholipid antibodies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Women with known aPL (i.e. isolated aPL or APS) who are planning pregnancy. aPL are defined by the presence of a positive test for anticardiolipin antibodies (IgG/IgM isotypes > 95th percentile) and/or lupus anticoagulant and/or anti- beta 2 glycoprotein-I (IgG/IgM isotypes > 95th percentile), on two or more consecutive occasions more than 12 weeks apart (a positive aPL test is defined under ‘glossary and definitions’). The last positive test must be within 12 months of study entry.
2. Written informed consent to participate

Exclusion criteria 17

1. Women who are already pregnant
2. Other severe active co-morbidities (including but not limited to HIV, hepatitis B, significant gastrointestinal, liver, cardiac, neurological,or hematological disorders or kidney disease with an eGFR below 30ml/min in which the treating physician would advise against pregnancy)
3. Porphyria
4. History of retinopathy or newly diagnosed retinopathy
5. History of galactose intolerance, lactase deficiency or glucose-galactose malabsorption
6. History of glucose-6-dehydrogenase deficiency
7. Participation in any other IMP trial at the time of consent
8. Previous pregnancy failure on hydroxychloroquine
9. Allergy or adverse event to hydroxychloroquine. Hypersensitivity to the active substance, 4- aminoquinoline or any of the compounds of the IMP or placebo.
10. Current treatment with hydroxychloroquine
11. Age < 18 years and > 45 years
12. Body weight < 45 kg
13. Psoriasis
14. Uncontrolled epilepsy
15. Anti-Ro antibodies
16. Renal replacement therapy
17. Women taking QT prolonging medications at screening will be excluded if QT prologation is identified at baseline ECG

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is a composite of three principal aPL-related adverse pregnancy outcomes: one or more pregnancy loss(es) (either < 10 weeks gestation or beyond 10 weeks of gestation of a morphologically normal fetus documented by ultrasound or by direct examination of the fetus) and premature birth of a morphologically normal neonate before 34 weeks due to any of: preeclampsia, eclampsia, recognized features of placental insufficiency

Secondary endpoints 12

1. Pregnancy loss < 10 weeks gestation
2. Pregnancy loss > 10th week of gestation of a morphologically normal fetus documented by ultrasound or by direct examination of the fetus
3. Premature birth of a morphologically normal neonate < 34 weeks due to any of: pre-eclampsia, eclampsia, recognized features of placental insufficiency
4. Gestational age at delivery
5. Birth weight
6. Delivery by Caesarean section
7. Apgar score < 7 at 5 min
8. Neonatal morbidity (bleeding or thrombotic complications, infections, congenital abnormalities)
9. Days to hospital discharge following delivery (mother & child)
10. Thrombotic events in the mother during pregnancy and 6 weeks post-partum.
11. Days of neonate in special care
12. Safety and tolerability of hydroxychloroquine in the mother and in the neonate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Clinical Trial Information

Public contact point

Organisation

Rigshospitalet

Contact name

Clinical Trial Information

Third parties 1

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications