A study to evaluate the efficacy and safety of AMY109 in women with endometriosis
| ISRCTN | ISRCTN15654320 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15654320 |
| EudraCT/CTIS number | 2023-507289-14-00 |
| IRAS number | 1006385 |
| Secondary identifying numbers | AMY106EU, IRAS 1006385, CPMS 54010 |
- Submission date
- 11/10/2022
- Registration date
- 15/05/2023
- Last edited
- 04/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
Endometriosis is a chronic gynaecological disorder associated with pelvic pain and infertility. The disease is not only dependent on the female hormone estrogen-dependent but is also an inflammatory gynaecological disorder Women can be treated with pain relief medication and/or hormone treatment. Sometimes the endometriosis tissue is removed by surgery to help relieve
symptom. If the inflammation can be treated it is thought that pain may be reduced and infertility symptoms could improve.
This study looks at whether an experimental drug called AMY109 can reduce the inflammation and pain caused by endometriosis when it is given, either on its own, or in combination with desogestrel (a progesterone only contraceptive pill) compared to desogestrel alone. Treatment will be assigned randomly to one of three groups with a 37.5% chance of being placed in groups 1 and 2 and a 25% chance of being put into group 3.
• Group 1: AMY109 & desogestrel-placebo
• Group 2: AMY109 and desogestrel
• Group 3: AMY109-placebo & desogestrel
Placebo is a dummy drug which looks the same as the active form but contains no active ingredient.
Who can participate?
Women who are generally in good health and who have endometriosis diagnosed via a laparoscopy but who haven’t yet had surgery to remove endometrial tissue within 9 months. Approximately 80 patients will be enrolled from approximately 8 centres in the United Kingdom (UK).
What does the study involve?
Eligible women from participating or referral centres will be invited to join the study. Firstly, there will be a washout period of between 4 and 12 weeks where certain medications will be stopped so that they are removed from the body. This will be followed by a screening period which could last up to 45 days to check that the participant is eligible for the study. Eligible participants will then receive AMY109 or a dummy drug for up to 52 weeks. They will also be asked to take either desogestrel or a dummy pill every day. Four weeks after the treatment has finished, the endometriosis will be removed surgically via laparoscopy where small incisions are made near the belly button or bikini line. Follow-up visits will be on Weeks 60, 77, 89 and 105. The total duration of the study will be a maximum of 29 months, including approximately 22 hospital visits.
The severity of the endometriosis will be measured during the course of the study by using MRI scans (up to three times) and up to three trans vaginal ultrasounds (ultrasound using a probe inserted into the vagina). It will also be measured by examination of images of the endometrial tissue before and after treatment and by examination of removed endometrial tissue and fluid at the time of surgery.
Eligibility assessments at the start of the study and ongoing safety assessments will include up to three chest X-rays and up to seven electrocardiograms (ECGs). Vital signs (blood pressure, body temperature and heart rate) will be measured at every visit and blood samples will be taken to assess both the health of the participant and also to look at how the drug is processed by the body, how the body responds to the drug and whether the body is making any antibodies to the drug. The total amount of blood collected during this study may be approximately 400 mL (about 3-8 teaspoons at each visit).
Participants will have to use the pain medication provided as part of the study and also agree to use two forms of barrier contraception from consent (for example, a combination of male condom with either cap, diaphragm or sponge with spermicide).
Participants will also be asked to complete a daily diary either using an App on their own phone or a handheld device. There will be questions related to how they are feeling, quality of life, any vaginal bleeding, the level of pain experienced, and the amount of pain medication taken each day.
What are the possible benefits and risks of participating?
AMY109 is an experimental drug so there are no known health benefits at this time. Because there is limited testing in humans, there may be side effects that are not known at this time.
The most common events observed in healthy volunteers receiving AMY109 were throat pain (oropharyngeal pain), sore throat (pharyngitis), and infection of the upper respiratory tract i.e. nose, nasal cavity or throat.
The most common side effects observed in patients with endometriosis receiving AMY109 were vomiting, anaemia, diarrhoea, throat pain (oropharyngeal pain), nausea, and symptoms of common cold (nasopharyngitis).
The most common side effects observed in patients with cancer who were receiving AMY109 were fever (pyrexia), constipation, diarrhoea, increased liver enzymes (aspartate aminotransferase) and anaemia.
AMY109 is a type of drug known as a biological agent. Theoretical risks include the possibility of causing hypersensitivity, infusion reaction, or anaphylactic reaction (a type of allergic reaction that could be serious), from a mild rash to a life-threatening reaction and could also possibly make it easier to get infections (for example respiratory infections) or delay wound healing. As there may be a risk in exposing an unborn child to study drug participants have to agree to use two forms of barrier contraception throughout the study and follow up.
There are also some risks with taking desogestrel, the most common risks (noted in about 1 in 10 women) include altered mood, depressed mood, decreased sexual drive (libido), headache, nausea, acne, breast pain, irregular or no menstruation and increased body weight.
Where is the study run from?
The study is expected to run in around 8 sites in the UK
When is the study starting and how long is it expected to run for?
October 2023 to September 2026
Who is funding the study?
The study is sponsored by Chugai Pharmaceuticals Ltd (UK)
Who is the main contact?
Mr Edward Morris, edward.morris@nnuh.nhs.uk
Mr Paul Simpson, paul.simpson@nnuh.nhs.uk
Contact information
Principal Investigator
Colney Lane
Norwich
NR4 7UY
United Kingdom
| Phone | +44 1603 286829 |
|---|---|
| edward.morris@nnuh.nhs.uk |
Study information
| Study design | Interventional double-blind randomized parallel-group controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A phase II, randomized, double blind study to evaluate the efficacy and safety of AMY109 in women with endometriosis |
| Study acronym | ACERS |
| Study objectives | Primary objective: To evaluate the efficacy of both (i) AMY109 and (ii) AMY109 and desogestrel compared with (iii) desogestrel in disease severity assessed by laparoscopic appearance in women with endometriosis Secondary objectives: 1. To evaluate the efficacy of both (i) AMY109 and (ii) AMY109 and desogestrel compared with (iii) desogestrel in disease severity assessed by magnetic resonance imaging (MRI). 2. To evaluate the efficacy of both (i) AMY109 and (ii) AMY109 and desogestrel compared with (iii) desogestrel in disease severity assessed by transvaginal ultrasound (TVUS). 3. To evaluate the efficacy of both (i) AMY109 and (ii) AMY109 and desogestrel compared with (iii) desogestrel on endometriosis associated pain. 4. To assess the safety and tolerability of both (i) AMY109 and (ii) AMY109 and desogestrel compared with (iii) desogestrel 5. To evaluate the pharmacokinetics (PK) in plasma and pharmacodynamics (PD) profile of AMY109 6. To assess the immunogenicity of AMY109 (induction of anti-AMY109 antibodies). |
| Ethics approval(s) |
Approved 27/03/2023, North East - Newcastle & North Tyneside 2 Research Ethics Committee (NHS BT Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)207 104 8086; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 22/ES/0045 |
| Health condition(s) or problem(s) studied | Endometriosis |
| Intervention | Period 1: 4–12-week washout period, required for participants receiving certain types of medication. Period 2: 21–45-day screening period, to confirm participant eligibility for the study. Period 3: 52-week treatment period, for participants to receive study treatment. Period 4: a post-treatment follow-up period, 52 weeks after the last dose of study drug to assess long-term safety of AMY109. Participants will be randomised in a 3:3:2 ratio to one of the following treatment groups: 1. AMY109, and desogestrel-placebo. A placebo looks like a medicine but does not contain any active ingredients 2. AMY109 and desogestrel 3. AMY109-placebo and desogestrel 4. AMY109 or AMY109-placebo will be administered every 4 weeks intravenously (directly into the vein) 5. Desogestrel will be administered daily orally (by mouth). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | AMY109, Desogestrel |
| Primary outcome measure | Changes of total score and stage in the revised American Society of Reproductive Medicine (r-ASRM) score assessed by laparoscopy from pre-treatment to post-treatment (Baseline and Week 53) |
| Secondary outcome measures | 1. Change in size of ovarian endometrioma assessed by MRI from baseline to Week 37 and 53. 2. Change in size of endometriotic nodule assessed by MRI from baseline to Week 37 and 53. 3. Change in adhesions assessed by MRI from baseline to Week 37 and 53. 4. Change of grade in the ENZIAN classification assessed by MRI from baseline to Week 37 and 53. 5. Change in the MEDL score assessed by MRI from baseline to Week 37 and 53. 6. Change in size of ovarian endometrioma from baseline to Week 25 and 53 assessed by transvaginal ultrasound (TVUS) 7.Change in size of endometriotic nodule from baseline to Week 25 and 53 assessed by TVUS 8. Change in adhesions from baseline to Week 25 and 53 assessed by TVUS 9. Change in monthly mean endometriosis associated pain scores (dysmenorrhea, dyspareunia, and NMPP) from baseline to each month as recorded by daily completion of an 11–point numerical rating scale (NRS) using an electronic diary (Baseline and then monthly up to Week 105) 10. Change in monthly mean endometriosis associated pain scores (dysmenorrhea, dyspareunia, and NMPP) from baseline to each month measured by the modified Biberoglu and Behrman Scale (mBBS) using an electronic diary on daily basis (Baseline and then monthly up to Week 105) 11. Change in monthly mean number of days of analgesics use to treat endometriosis associated pain from baseline to each month as recorded by daily completion of an electronic diary (Baseline and then monthly up to Week 105) 12. Change in monthly mean dose of analgesics use to treat endometriosis associated pain from baseline to each month as recorded by daily completion of an electronic diary (Baseline and then monthly up to Week 105) 13. Incidence and severity of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and adverse drug reactions up to Week 105 14. Vital signs (pulse rate, blood pressure, body temperature). Screening until Week 105. 15.12-lead electrocardiograms (ECGs). Screening until Week 53. 16. Laboratory investigations (urinalysis, hematology, blood chemistry, coagulation tests, and other investigations). Screening until Week 105 17. Plasma concentration of AMY109 and IL-8. Screening until Week 105 18. Ovarian function measured by uterine bleeding and serum level of anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), estradiol (E2), and progesterone (P4). Week 1 until Week 53 19. Plasma CA125. Week 1 until Week 53 20. Change in incidence of anti-AMY109 antibodies. Week 1 until Week 105 21. Change in plasma concentration of AMY109 and total IL-8 by anti-AMY109 antibody status (seropositive or seronegative) up to Week 105 |
| Overall study start date | 06/10/2022 |
| Completion date | 05/09/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 49 Years |
| Sex | Female |
| Target number of participants | 120 |
| Key inclusion criteria | Current inclusion criteria as of 25/04/2024: 1. Provide written informed consent and sign the Informed Consent Form 2. Female patients between 18 and 49 years of age inclusive at entering the screening period 3. Patients who have received a laparoscopic diagnosis within 9 months before entering the screening period but have not received any surgical treatment at the laparoscopic diagnosis. 4. Able to comply with study requirements in the Investigator’s judgment 5. Agree to use non-hormonal, double-barrier contraception such as a combination of male condom with either cap, diaphragm or sponge with spermicide and refrain from egg collection for preservation or donation. 6. Agree to switch from usual analgesics for dysmenorrhea, dyspareunia, and NMPP to analgesics permitted by the study protocol 7. Patients who are willing to have laparoscopic surgery after study treatment is completed and understands the surgery may be delayed by participation in the study. 8. Has at least 1 full menstrual cycle (21-38 days) during the screening period. The withdrawal bleeding while cyclically using hormonal agents is not considered regular menses 9. Has at least 21 days of e-Diary entries during the screening period and completed the e-Diary on at least 75% of days during the screening period. Note: e-Diary vendor will provide an e-Diary compliance report. The investigational site should review the report before randomization to assess eligibility. 10. Has moderate to severe endometriosis-associated NMPP (NRS score of ≥4 on ≥ 4 days of the screening period) and dysmenorrhea (NRS score of ≥4 on ≥ 2 days of the screening period) 11. Patients who are staged III/IV endometriosis according to the revised American Society of Reproductive Medicine (r-ASRM) score by central readers based on images obtained at the laparoscopic diagnosis _____ Previous inclusion criteria: 1. Provide written informed consent and sign the Informed Consent Form 2. Female patients between 18 and 45 years of age inclusive at entering the screening period 3. Patient who is diagnosed as having endometriosis by laparoscopy, but have not yet received any surgical treatment at the diagnosis, within 6 months before entering the screening period and who is staged according to the revised American Society of Reproductive Medicine (r-ASRM) score by central readers based on images obtained at the laparoscopic diagnosis 4. Not suitable for surgical treatment at laparoscopic diagnosis due to severe condition of the disease 5. Able to comply with study requirements in the Investigator’s judgment 6. Agree to use non-hormonal, double-barrier contraception such as a combination of male condom with either cap, diaphragm or sponge with spermicide and refrain from egg collection for preservation or donation until 32 weeks after the last administration of AMY109 or AMY109-placebo 7. Agree to switch from usual analgesics for dysmenorrhea, dyspareunia, and NMPP to analgesics permitted by the study protocol 8. Patient is willing to have laparoscopic surgery after study treatment is completed and understands the surgery will be delayed by participation in the study. Patients must also meet the following criteria for study entry (in addition to 1-8 above): 9. Has at least 1 full menstrual cycle (21-38 days) during the screening period. The withdrawal bleeding while cyclically using hormonal agents is not considered regular menses 10. Has at least 21 days of e-Diary entries during the screening period and completed the e-Diary on at least 75% of days during the screening period.. Note: e-Diary vendor will provide an e-Diary compliance report. The investigational site should review the report before randomization to assess eligibility. 11. Has moderate to severe endometriosis-associated NMPP (NRS score of ≥4 on ≥ 4 days of the screening period) and dysmenorrhea (NRS score of ≥4 on ≥ 2 days of the screening period) |
| Key exclusion criteria | 1. Clinically significant abnormalities in laboratory test results, physical examination, vital signs, 12-lead ECG, chest X-ray, hematology (e.g., Hemoglobin [Hb] < 90 g/L), blood chemistry, serology, and urinalysis at screening. 2. Patient has chronic pelvic pain that is not caused by endometriosis and that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain (e.g. pelvic inflammatory disease). 3. Patient has a surgical history of hysterectomy and/or bilateral oophorectomy. 4. Prior treatment with antibody preparations (commercially available or investigational) within 6 months or 5 half-lives of the drug, whichever is longer, before entering the screening period 5. Prior treatment with anti-IL-8 antibody preparations |
| Date of first enrolment | 10/01/2024 |
| Date of final enrolment | 31/07/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Norwich
NR4 7UY
United Kingdom
Colchester
CO4 5JL
United Kingdom
London
SE1 7EH
United Kingdom
Jessop Wing
Tree Root Walk
Sheffield
S10 2SF
United Kingdom
369 Fulham Road
London
SW10 9NH
United Kingdom
Sponsor information
Industry
Mulliner House
Flanders Road
London
W4 1NN
England
United Kingdom
| Phone | +44 20 8987 5600 |
|---|---|
| regulatory@chugai-pharm.co.uk |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 05/09/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Submission to regulatory authorities Investigators will be informed of study results and may pass on the details to participants |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Editorial Notes
04/10/2024: The study participating centre Chelsea and Westminster Hospital was added.
02/10/2024: Study website added.
30/09/2024: St Thomas' Hospital and Royal Hallamshire Hospital were added to the study participating centres.
25/04/2024: The following changes were made to the trial record:
1. The acronym was added.
2. The EudraCT/CTIS number was changed from 2021-006583-24 to 2023-507289-14-00.
3. The inclusion criteria were changed.
4. The target number of participants was changed from 80 to 120.
5. The recruitment start date was changed from 31/03/2023 to 10/01/2024.
6. The recruitment end date was changed from 30/09/2024 to 31/07/2025.
7. The study participating centres were added.
8. The plain English summary was updated to reflect these changes.
27/11/2023: Ethics approval details added.
27/07/2023: The target number of participants was changed from 63 to 80.
05/06/2023: Internal review.
11/10/2022: Trial's existence confirmed by NHS HRA.
