Healthy Volunteers, Vasomotor Symptoms Associated With Menopause
Conditions
Brief summary
The purpose of this study is to evaluate the effects of single and multiple doses of ABCL635 administered by subcutaneous (SC) injection to healthy men and to postmenopausal women with or without any vasomotor symptoms (VMS) or hot flashes, and to postmenopausal women with moderate-to-severe VMS associated with menopause. The safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters of ABCL635 will be assessed in all study participants; the effects on frequency and severity of VMS will be assessed in postmenopausal women who experience moderate-to-severe symptoms.
Detailed description
The study consists of 3 parts: Part A and Part B (Phase 1) and Part C (Phase 2). In Part A, single ascending doses (SAD) of ABCL635 or placebo will be administered to healthy male and female participants. In Part B, up to 3 multiple ascending doses (MAD) of ABCL635 or placebo will be administered to healthy postmenopausal women with or without VMS. In Part C, a single dose of ABCL635 or placebo will be administered to postmenopausal women experiencing moderate-to-severe VMS associated with menopause. In Part C, all participants will be offered to participate in an open label extension (OLE) cohort and receive a single dose of ABCL635 upon completion of a 12-week assessment.
Interventions
BIOLOGICALABCL635
Participants will receive SC administrations of ABCL635
BIOLOGICALPlacebo
Participants will receive SC administration of placebo (5% dextrose solution)
Sponsors
AbCellera Biologics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Good general health as determined through a review of their medical history and after conducting a general physical examination * Body weight ≥ 45 to ≤ 120 kg * Body mass index (BMI) between 18.5 kg/m2 and 35.0 kg/m2 * Non- or ex-smoker (an ex-smoker is defined as someone who completely stopped using nicotine products for at least 90 days prior to the first study drug administration) * Healthy man or a postmenopausal woman who is ≥ 40 and ≤ 75 years of age OR a postmenopausal woman with or without VMS and who is ≥ 40 and ≤ 75 years of age OR a postmenopausal woman who is ≥ 40 and ≤ 75 years of age seeking treatment for relief for VMS * If a woman: 1. has been compliant with local and/or national guidelines for breast cancer screening with documentation of a mammogram with normal/negative or no clinically significant findings. A screening mammogram may be conducted during study screening period, if needed 2. has spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (follicle-stimulating hormone \[FSH\] \> 40 IU/L); or had a bilateral oophorectomy \> 6 weeks prior to screening, or s/p hysterectomy at least 6 weeks prior to screening and meeting the biochemical criteria of menopause (FSH \> 40 IU/L) * If a man: 1. possess a testosterone concentration of ≥ 15 nmol/L at the time of screening 2. can procreate and agree to use one of the acceptable contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration OR is unable to procreate; defined as surgically sterile
Exclusion criteria
* Pregnancy and/or lactation. * Has endometrial hyperplasia or history of abnormal uterine bleeding without an identified cause in the past 6 months * Previous or current history of a malignant tumor, except for non-melanoma skin cancer. * Seated pulse rate less than 50 beats per minute (bpm) or more than 100 bpm or a seated blood pressure \< 90/50 mmHg or \> 140/90 mmHg * eGFR \< 60 mL/min/1.73 m2 * Severe hypersensitivity reactions (like angioedema) to any drugs. * Significant uncontrolled cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease. * Clinically significant ECG abnormalities * Presence or history of cardiogenic syncope in the past 6 months. * Use of any over-the-counter products (including supplements) containing testosterone or any medication (hormonal, prescription, over the counter, herbal, or natural) for the treatment of hot flashes during the screening period and throughout the study; must be discontinued at least 28 days prior to study drug administration * Employees of the sponsor or the investigator site and other individuals who are directly involved in the conduct of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of adverse events (AE) | Day 0 to day 197 |
| Number of participants with abnormalities in 12-lead safety electrocardiograms (ECG) | Day 0 to day 197 |
| Number of participants with abnormalities in physical examination | Day 0 to day 197 |
| Number of participants with abnormalities in laboratory parameters, including general biochemistry, hematology, endocrinology, and urinalysis | Day 0 to day 197 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline to each study week in the frequency of moderate and severe VMS (VMSM-S frequency) | up to day 141 (Part C) | — |
| Mean change from baseline to each study week in the severity of moderate and severe VMS (VMSM-S severity) | up to day 141 (Part C) | — |
| Mean change from baseline to each study week in the frequency of all reported VMS (VMSTotal frequency). | up to day 141 (Part C) | — |
| Mean change from baseline to each study week in the moderate to severe hot flash score (HFM-S). | up to day 141 (Part C) | The moderate to severe hot flash score (HFM-S) is a metric that combines the frequency and severity of hot flashes: * The daily score is calculated as follows: (number of moderate hot flashes x 2) + (number of severe hot flashes x 3) * The weekly score is the average daily score over seven days. A negative change in the score from Baseline to Week 1 indicates a reduction in the severity and frequency of hot flashes |
| Mean change from baseline to each study week in the total hot flash score (HFTotal). | up to day 141 (Part C) | The total hot flash score (HFTotal) is a metric that combines the frequency and severity of hot flashes: * The daily score is calculated as follows: (number of mild hot flashes x 1) + (number of moderate hot flashes x 2) + (number of severe hot flashes x 3) * The weekly score is the average daily score over seven days. A negative change in the score from Baseline to Week 1 indicates a reduction in the severity and frequency of hot flashes. |
| Mean change in the Menopause-Specific Quality of Life Questionnaire (MENQOL) 4-domain scores (ie, physical, vasomotor, psychosocial, and sexual) from baseline to weeks 1, 2, 3, 4, 5, 9, and 13 | up to day 141 (Part C) | The Mean change in the Menopause-Specific Quality of Life Questionnaire (MENQOL) measures the impact of menopause symptoms over the last week. The questionnaire has 29 items across four domains: vasomotor (items 1 to 3), psychosocial (items 4 to 10), physical (items 11 to 26), and sexual (items 27 to 29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a 0 (not bothersome) to 6 (extremely bothersome) scale. The mean change in the MENQOL domain scores will be assessed from Baseline to each week measured. A negative change in the score from Baseline to each week measured indicates an improvement in quality of life. |
| Mean change in the Patient-Reported Outcomes Measurement Information System Sleep Disturbance 8b Short Form (PROMIS-SD-SF-8b) total score from baseline to weeks 1, 2, 3, 4, 5, 9, and 13. | up to day 141 (Part C) | The PROMIS-SD-SF-8b assesses the perception of sleep quality, sleep depth, and any perceived difficulties related to getting and staying asleep. Questions are scored using the following scale: 1 (very much), 2 (quite a bit), 3 (somewhat), 4 (a little bit), and 5 (not at all). The mean change in the PROMIS-SD-SF-8b score will be assessed from Baseline to each week measured. A positive change in the score from Baseline to each week measured indicates a reduction in sleep disturbance. |
| Frequency of Patient Global Impression of Change in VMS (PGI-C VMS) responses at weeks 2, 3, 4, 5, 9, and 13. | up to day 141 (Part C) | The Patient Global Impression of Change (PGI-C) for vasomotor symptoms (VMS) rates the perception of their hot flashes and night sweats at each designated timepoint compared to the start of the study. The response is a seven-point scale ranging from "much better" to "much worse." The frequency of each PGI-C VMS score will be reported at each scheduled timepoint. |
| Plasma concentrations of ABCL635 | Day 0 to day 197 | — |
| Incidence of anti-ABCL635 antibodies | Day 0 to day 197 | — |
| PK parameters; maximum plasma concentration (Cmax) | Day 0 to day 197 | — |
| PK parameters; time to maximum plasma concentration (Tmax) | Day 0 to day 197 | — |
| PK parameters; area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC0-T) | Day 0 to day 197 | — |
| PK parameters; area under the plasma concentration-time curve from zero to hour 672 (AUC0-672) | Day 0 to day 197 | — |
| PK parameters; area under the plasma concentration-time curve from zero to infinity (AUC0-∞) | Day 0 to day 197 | — |
| PK parameters; percent of AUC obtained by extrapolation (%AUCextrap) | Day 0 to day 197 | — |
| PK parameters; terminal rate constant (λz) | Day 0 to day 197 | — |
| PK parameters; apparent plasma clearance of drug after extravascular administration (CL/F) | Day 0 to day 197 | — |
| PK parameters; apparent volume of distribution after extravascular administration (Vz/F) | Day 0 to day 197 | — |
| PK parameters; half-life (Thalf) | Day 0 to day 197 | — |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATOREric Sicard
Altasciences Company Inc.
Outcome results
None listed