A pivotal, multicentre, randomised, open-label, parallel-group trial on contraceptive efficacy, safety and tolerability of LVDS (Levonorgestrel Vaginal Delivery System) during 9 cycles in comparison with Desogestrel tablets 0.075 mg.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chemo Research S.L.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]

Trial duration

12 Jul 2023 → 26 Mar 2025

Decision date (initial)

2023-07-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Chemo Research S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To demonstrate the contraceptive efficacy of LVDS.

Secondary objectives 2

1. [Secondary efficacy:] To demonstrate the contraceptive efficacy of LVDS.
2. [Secondary safety and tolerability:] To demonstrate the safety and tolerability of LVDS.

Conditions and MedDRA coding

Prevention of pregnancy

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. [Visit 1a:] Sexually active, postmenarcheal and premenopausal female subjects ≥ 18 years at risk of pregnancy including breastfeeding women.
2. [Visit 1a:] Women who either a. have never used hormonal contraceptives before consent (naïve users), or b. have used hormonal contraceptives in the past, but have had a hormonal contraceptive-free period before consent and a full menstrual cycle during the drug-free period (previous users) or c. directly switch from another hormonal contraceptive (switchers).
3. [Visit 1a:] Only for subjects who were not pregnant and did not use hormonal contraception during the last 6 months before consent: Regular cycles (i.e. cycle length between 24 and 35 days) during the last 6 months.
4. [Visit 1a:] Only for women who were pregnant within the last 6 months before consent: At least 3 complete menstrual cycles after pregnancy. Breastfeeding women can be included 4 weeks after delivery irrespective of menstrual cycles post-delivery.
5. [Visit 1a:] Systolic blood pressure ≤ 140 mm Hg and diastolic blood pressure ≤ 90 mm Hg, subjects with controlled hypertension are allowed.
6. [Visit 1a:] A written informed consent is available, prior to undergoing any trial-related procedure.
7. [Visit 1a:] Willing to use the trial contraception they were randomised to (vaginal ring or oral tablet) for nine 28-day cycles.
8. [Visit 1a:] Be willing to have intercourse in each cycle of the trial without the need to use back-up contraceptive.
9. [Visit 1a:] Be willing to state that, to her best knowledge, her male sexual partner/partners has/have not had a vasectomy or been previously diagnosed as infertile.
10. [Visit 1a:] Agree not to participate in any other clinical trials during the course of this trial (participation in a non-interventional study is allowed).

Exclusion criteria 20

1. [Visit 1a / Visit 1b:] Pregnancy or wish of pregnancy.
2. [Visit 1a:] Subject is known to or suspected of not being able to comply with the trial protocol, the use of the trial medication or the use of the trial diary.
3. [Visit 1a:] History of infertility.
4. [Visit 1a:] Known bleeding disorder or history of unexplained bleeding or bruising within the last 12 months prior to V1a.
5. [Visit 1a:] Unexplained amenorrhea.
6. [Visit 1a:] Abnormal finding on pelvic, breast or ultrasound examination that in the investigator’s opinion contraindicates participation in the trial.
7. [Visit 1a:] Women - with a Papanicolaou (Pap) smear reading low-grade squamous intraepithelial lesion (LGSIL) or higher at screening. Subjects with atypical squamous cells of undetermined significance (ASC-US) can be included if they are negative for high-risk human papilloma virus (HPV) strains.
8. [Visit 1a:] Known contraindication including: a. Active venous thromboembolic disorder and/or a VTE history including a known positive family history in a sibling or parent. b. Arterial and cardiovascular disease, past or present (e.g. myocardial infarction, cerebrovascular accident, ischemic heart disease). c. Major surgery with prolonged immobilisation. d. Diabetes mellitus with vascular involvement. e. Presence or history of severe hepatic disease as long as liver function values have not returned to normal. f. Presence or history of liver tumours (benign or malignant). g. Known severe renal insufficiency or acute renal failure. h. Known adrenal insufficiency. i. Known or suspected sex steroid sensitive malignancies, including breast cancer. j. Hypersensitivity to the active substance, soya, peanut or to any of the excipients. k. Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
9. [Visit 1a:] Uncontrolled concomitant chronic diseases (i.e., not on a stable treatment dose for at least 2 months at the time of consent).
10. [Visit 1a:] Severe COVID-19 disease or less than 3 months after hospitalization due to a COVID-19 disease.
11. [Visit 1a:] Known HIV infection.
12. [Visit 1a:] Known current or chronic hepatitis B or C.
13. [Visit 1a:] Gastrointestinal (malabsorptive) disease including inflammatory bowel disease (Crohn's disease or ulcerative colitis), gastric bypass surgery, current post gastrectomy syndrome and celiac disease.
14. [Visit 1a / Visit 1b:] Prohibited previous medication/therapy (as given in the protocol)
15. [Visit 1a / Visit 1b:] Dependence on prohibited co-medication/-therapy (as given in the protocol)
16. [Visit 1a / Visit 1b:] Progestin-releasing intra-uterine device (IUD) or contraceptive implant received or in place within the last 2 months.
17. [Visit 1a:] Planned regular concomitant use of barrier contraceptive methods, spermicides, IUDs or other contraceptive measures.
18. [Visit 1a:] Subject is a member of the investigator’s or sponsor’s staff or a relative or family member thereof.
19. [Visit 1a:] Is in custody or submitted to an institution by a court order.
20. [Visit 1a / Visit 1b:] Any condition or any disease that, in the opinion of the investigator, may jeopardize protocol compliance or the scientific integrity of the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Pearl Index (PI) in non-breastfeeding women aged ≤ 35 years (at the time of trial enrolment).

Secondary endpoints 22

1. [Secondary efficacy:] Overall PI in women aged ≤ 35 years and in women > 35 years (at the time of trial enrolment).
2. [Secondary efficacy:] PI after correction for back-up contraception and sexual activity (evaluable cycles).
3. [Secondary efficacy:] PI after correction for back-up contraception and sexual activity (evaluable cycles) in women aged ≤ 35 years and in women > 35 years (at the time of trial enrolment).
4. [Secondary efficacy:] PI for method failure.
5. [Secondary efficacy:] PI for method failure in women aged ≤ 35 years and in women > 35 years (at the time of trial enrolment).
6. [Secondary efficacy:] Pregnancy ratio by life table analysis.
7. [Secondary efficacy:] Pregnancy ratio by life table analysis in women aged ≤ 35 years and in women > 35 years (at the time of trial enrolment).
8. [Secondary safety and tolerability:] Adverse events (AEs).
9. [Secondary safety and tolerability:] Vital Signs.
10. [Secondary safety and tolerability:] Physical examination.
11. [Secondary safety and tolerability:] Gynaecological examination, incl. transvaginal ultrasound examination and cervical cytology.
12. [Secondary safety and tolerability:] Mastodynia/mastalgia/dysmenorrhea.
13. [Secondary safety and tolerability:] Proportion of subjects with bleeding during Cycles 2-9 (non-inferiority test, key secondary endpoint).
14. [Secondary safety and tolerability:] Proportion of subjects with bleeding / spotting in each cycle.
15. [Secondary safety and tolerability:] Proportion of subjects with absence of bleeding.
16. [Secondary safety and tolerability:] Proportion of subjects with prolonged bleeding.
17. [Secondary safety and tolerability:] Number of days per cycle and reference period with bleeding and with spotting.
18. [Secondary safety and tolerability:] Number of bleeding / spotting episodes per reference period.
19. [Secondary safety and tolerability:] Duration of bleeding / spotting episodes by cycle and reference period.
20. [Secondary safety and tolerability:] Clinical laboratory parameters (haematology, biochemistry including estradiol levels, TSH and urinalysis; in a subset of subjects: haemostatic variables, carbohydrate metabolism, bone mineral density biomarkers, SHBG).
21. [Secondary safety and tolerability:] IP acceptability.
22. [Secondary safety and tolerability:] Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF).

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chemo Research S.L.

Sponsor organisation

Chemo Research S.L.

Address

3rd Floor, Calle De Manuel Pombo Angulo 28 Calle De Manuel Pombo Angulo 28

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Chemo Research S.L.

Contact name

Chief Scientific Officer

Public contact point

Organisation

Chemo Research S.L.

Contact name

Chief Scientific Officer

Third parties 12

Locations

8 EU/EEA countries · 72 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 264 files

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

Application history

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