A Study of the Safety and Effect of Repeated Administration of G-CSF on Hot Flashes in Postmenopausal Women

NCT03640754 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: MNGX-1021R43AG056209-01A1
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the efficacy and safety of repeated administration of G-CSF for the treatment of hot flashes and vasomotor symptoms in women with naturally-occurring or surgically induced menopause. G-CSF will be administered three times at 28 day intervals to postmenopausal women, ages 40 to 65, suffering at least 49 moderate to severe hot flashes per week.

Conditions

Postmenopausal Symptoms

Keywords

Hot Flashes; Vasomotor Symptoms; Menopause

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Adverse Events

  An adverse event (AE) is any untoward medical occurrence, including the exacerbation of a pre-existing condition, in a subject or clinical investigation subject administered a pharmaceutical product. This does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect, or precaution. This includes any experience that results in death; is acutely life-threatening; requires inpatient hospitalization or prolongs the existing hospitalization; results in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; is a congenital anomaly/birth defect; or requires medical or surgical intervention to prevent one of the outcomes listed above.

  From first dose date up to 30 days after last dose (up to 16 weeks)

• Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 0

  Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 0. Blood samples were collected 24 hours after adminstration of G-CSF on day 0.

  Baseline and day 1

• Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 28

  Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 28. Blood samples were collected 24 hours after adminstration of G-CSF on day 28.

  Baseline and day 29

• Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 56.

  Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 56. Blood samples were collected 24 hours after adminstration of G-CSF on day 56.

  Baseline and day 57

• Change From Baseline in White Blood Cell Counts on Day 84 (28 Days After Last Administration of G-CSF or Palcebo)

  Change from baseline in white blood cell counts on day 84. Blood samples were collected 24 hours after adminstration of G-CSF on day 84.

  Baseline and day 84

• Change From Baseline in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes at Week 4

  The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 4

• Change From Baseline in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes at Week 12

  The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 12

• Change From Baseline in the Mean Composite Daily Severity of Hot Flashes (CDS) at Week 4

  CDS (Composite Daily Hot Flash Severity) was calculated as follows: \[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)\]. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 4

• Change From Baseline in the Mean Composite Daily Severity of Hot Flashes (CDS) at Week 12

  CDS (Composite Daily Hot Flash Severity) was calculated as follows: \[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)\]. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 12

• Change From Baseline in the Mean Daily Severity of Hot Flashes (HFSS) at Week 4

  HFSS (Daily Hot Flash Severity Score) was calculated as follows: \[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)\]/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 4

• Change From Baseline in the Mean Daily Severity of Hot Flashes (HFSS) at Week 12

  HFSS (Daily Hot Flash Severity Score) was calculated as follows: \[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)\]/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

  Baseline and week 12

Secondary Outcomes (9)

• Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12

  Weeks 1-12

• Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12

  Weeks 1-12

• Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12

  Weeks 1-12

• Percent Change in M+S at 12 Weeks in Demographic Subgroups

  Baseline and Week 12

• Net Change in HFSS at 12 Weeks in Demographic Subgroups

  Baseline and Week 12

Study Arms (2)

Experimental: G-CSF

ACTIVE COMPARATOR

Intervention: G-CSF given by subcutaneous injection repeated 3 times (Days 0, 28, 56) Other name: Filgrastim

Biological: G-CSF

Comparator: Placebo/Saline

PLACEBO COMPARATOR

Intervention: Placebo/saline given by subcutaneous injection repeated 3 times (Days 0, 28, 56) Other name: Saline

Other: Placebo/Saline

Interventions

G-CSF BIOLOGICAL

G-CSF injected subcutaneously 3 times (Days 0, 28, 56)

Also known as: Filgrastim

Experimental: G-CSF

Placebo/Saline OTHER

Placebo/saline injected subcutaneously 3 times (Days 0, 28, 56)

Also known as: Saline

Comparator: Placebo/Saline

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, aged 49 to 65 for natural postmenopausal or aged 40 to 65 for surgical postmenopausal
• Body Mass Index (BMI) 18 to 35
• At least 7 moderate to severe hot flashes per day on average (or at least 49 moderate to severe hot flashes per week)
• Naturally postmenopausal or surgically postmenopausal women:
• Naturally postmenopausal is defined as having no menstrual periods for at least 12 months prior to study entry; with a biochemical criteria of menopause (FSH \>40 IU/L)
• Surgically postmenopausal is defined as at least 3 months after documented bilateral salpingo oophorectomy
• Normal pelvic exam and pap smear within 2 years
• Signed informed consent

You may not qualify if:

• Radiation or chemotherapy-induced (including gonadotropin-releasing hormone (GnRH) agonist) menopause
• Prior chemotherapy or radiation therapy for cancer
• Prior diagnosis of hematologic malignancy
• Type 1 diabetics or Type 2 diabetics with HbA1c \> 7.0%
• Use of hormone replacement therapy or oral contraceptives within the past three months
• Use of alternative or complementary medicines or herbs for menopausal symptoms within 30 days (refer to Appendix 2)
• Use of any selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) within 30 days
• Use of selective estrogen receptor modulators within 30 days
• Use of gabapentin within 30 days
• Use of clonidine within 30 days
• Use of megestrol acetate (Megace) within 30 days
• Use of, prescription corticosteroids within 30 days (nasal or other inhaled corticosteroids and over-the-counter (OTC) hydrocortisone ointment or cream excepted)
• Current use of lithium therapy (related to possible risk of G-CSF)
• History (in the past year) or presence of drug or alcohol use which, in the opinion of the Investigator, might compromise the study or confound the study results
• History of use of any anti-inflammatory biologics

Sponsors & Collaborators

• MenoGeniX, Inc.: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Site 2

Aurora, Colorado, 80045, United States

Location

Site 1

Denver, Colorado, 80209, United States

Location

MeSH Terms

Conditions

Hot Flashes

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Sodium Chloride

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Debra Duke
• Organization: MenoGeniX

debra.duke@menogenix.com

303-995-7979

Study Officials

• Richard C Duke, PhD

  MenoGeniX, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 21, 2018
• Study Start: August 6, 2018
• Primary Completion: January 21, 2022
• Study Completion: February 22, 2022
• Last Updated: November 28, 2023
• Results First Posted: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)