Study Evaluating ABCL635 for Vasomotor Symptoms of Menopause

A First-in-Human Phase 1/2 Study of ABCL635 in Healthy Participants and in Postmenopausal Women With Moderate-to-Severe Vasomotor Symptoms

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers; Vasomotor Symptoms Associated With Menopause
• Intervention / Treatment: Biological: ABCL635; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4L7
      • CaRe Clinics
    • Red Deer, Alberta, Canada, T4P 1K4
      • CaRe Clinics
  • British Columbia
    • Vancouver, British Columbia, Canada, V5T 3N4
      • Mount Saint Joseph Hospital Clinical Trials Phase 1 Unit
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • Centricity Research
    • Toronto, Ontario, Canada, M4W 4L6
      • Centricity Research
  • Quebec
    • Lévis, Quebec, Canada, G6V 0C9
      • Alpha Recherche Clinique
    • Montreal, Quebec, Canada, H1Y 3H5
      • GCP Research
    • Mount Royal, Quebec, Canada, H3P 3P1
      • Altasciences Company Inc.
    • Québec, Quebec, Canada, G1V 4T3
      • Diex Recherche Québec
    • Québec, Quebec, Canada, G1V 3M8
      • Clinique RSF Inc.
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke
    • Trois-Rivières, Quebec, Canada, GSA 4P3
      • Diex Recherche Trois-rivieres
    • Victoriaville, Quebec, Canada, G6P 3Z8
      • Diex Recherche Victoriaville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABCL635 Part A; Part A: healthy male and female participants will receive a single dose of ABCL635 administered by subcutaneous (SC) injection	Biological: ABCL635; Participants will receive SC administrations of ABCL635
Placebo Comparator: Placebo Part A; Part A: Healthy male and female participants will receive a single dose of placebo (dextrose 5% solution) administered by SC injection	Biological: Placebo; Participants will receive SC administration of placebo (5% dextrose solution)
Experimental: ABCL635 Part B; Part B: healthy postmenopausal women with or without VMS will receive up to 3 doses of ABCL635 administered by SC injection	Biological: ABCL635; Participants will receive SC administrations of ABCL635
Placebo Comparator: Placebo Part B; Part B: healthy postmenopausal women with or without VMS will receive up to 3 doses of placebo (dextrose 5% solution) administered by SC injection	Biological: Placebo; Participants will receive SC administration of placebo (5% dextrose solution)
Experimental: ABCL635 Part C; Part C: postmenopausal women with moderate to severe VMS will receive a single dose of ABCL635 administered by SC injection	Biological: ABCL635; Participants will receive SC administrations of ABCL635
Placebo Comparator: Placebo Part C; Part C: postmenopausal women with moderate to severe VMS will receive a single dose of placebo (dextrose 5% solution) administered by SC injection	Biological: Placebo; Participants will receive SC administration of placebo (5% dextrose solution)
Experimental: ABCL635 Part C OLE; Part C open label extension (OLE): postmenopausal women with moderate to severe VMS will receive a single dose of ABCL635 administered by SC injection upon completion of 12-week assessment.	Biological: ABCL635; Participants will receive SC administrations of ABCL635

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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).	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	up to day 141 (Part C)
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	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.	up to day 141 (Part C)
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.	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.	up to day 141 (Part C)
Frequency of Patient Global Impression of Change in VMS (PGI-C VMS) responses at weeks 2, 3, 4, 5, 9, and 13.	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.	up to day 141 (Part C)
Mean change from baseline to each study week in the total hot flash score (HFTotal).	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.	up to day 141 (Part C)

Other Outcome Measures

Outcome Measure	Time Frame
Physiological PD parameters; change over time from baseline in LH and FSH (men and women), testosterone in men only, and estradiol in women only	Day 0 to day 197
PK-PD; Relationship between selected PK endpoints and relevant physiological and behavioral PD endpoints	Day 0 to day 197

Collaborators and Investigators

• Sponsor: AbCellera Biologics Inc.
• Investigators: Principal Investigator: Eric Sicard, Altasciences Company Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: July 16, 2025
• First Submitted That Met QC Criteria: August 5, 2025
• First Posted (Actual): August 12, 2025

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ABCL635-101; 297103 (Other Identifier: Health Canada CTA control number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes