Aldafermin (NGM282) for Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)

NCT05130047 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 21-009348
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, randomized, double-blind, placebo-controlled study is designed to compare effects of aldafermin, (NGM282), 1 mg, and placebo given daily by subcutaneous injection on bowel functions and hepatic synthesis and fecal excretion of bile acids in patients with diarrhea associated with bile acid malabsorption (BAM).

Conditions

Chronic Diarrhea; Irritable Bowel Syndrome With Diarrhea; Bile Acid Malabsorption; Bile Acid Diarrhea; Bile Acid Malabsorption Syndrome Type II; Functional Diarrhea

Outcome Measures

Primary Outcomes (2)

• Fasting Serum C4 Levels

  Fasting serum C4 is measured by liquid chromatography-mass spectrometry.

  28 days

• Change in Stool Consistency From Baseline to Day 28

  Stool consistency as reported by the patient in daily bowel pattern diaries. Stool consistency is based on Bristol Stool Form Scale (BSFS) 1: Hard lumps; 2:Lumpy sausage; 3: Cracked sausage; 4: Smooth sausage; 5: Soft lumps; 6: Mushy; 7: Watery. spectrometry.

  Baseline, 28 days

Secondary Outcomes (7)

• Stool Consistency

  14 days, 28 days

• Abdominal Pain Score

  baseline, 28 days

• Bowel Movements

  baseline, 28 days

• Proportion of Fecal Secretory (CDCA + DCA) Bile Acid as Measured in a Random Stool Sample by a Validated Laboratory Assay.

  Baseline, 14 days, 28 days

• Proportion of Fecal Primary (CDCA + CA) Bile Acid as Measured in a Random Stool Sample by a Validated Laboratory Assay.

  Baseline,14 days, 28 days

Study Arms (2)

Aldafermin (NGM282)

EXPERIMENTAL

Aldafermin (NGM282) is an investigational medication. It is an engineered analog of FGF-19 which reduces synthesis of bile acids and diarrhea caused by elevated bile acids. Participants receive aldafermin (NGM282) 1 mg given by subcutaneous injection once daily for 28 days.

Drug: Aldafermin

Placebo

PLACEBO COMPARATOR

A placebo looks exactly like the study drug but contains no active ingredients. It is used to learn if the effects seen are truly from the study drug. Participants receive placebo solution matching aldafermin (NGM282) given by subcutaneous injection once daily for 28 days.

Drug: Placebo

Interventions

Aldafermin DRUG

1 mg solution

Also known as: NGM282

Aldafermin (NGM282)

Placebo DRUG

Aldafermin placebo solution

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years, inclusive at Visit 1 Screen.
• Clinical diagnosis of functional diarrhea or IBS with diarrhea according to Rome III or IV criteria at Visit 1 Screen.
• Clinical laboratory evidence of BAM (20-22), with at least one of the following results recorded in their past medical history:
• Serum C4 ≥ 52 ng/mL
• Fecal BA \> 2337 µmoles / 48 hours
• Total fecal BA \> 1000 µmoles / 48 hours + 4 % primary BA
• Fecal primary BA \> 10% / 48 hours
• Body mass index (BMI) 18.0 to 45.0 kg/m2, inclusive at Visit 1 Screen
• Understands the study procedures, is willing and able to comply with the study procedures, and is able to give informed consent
• If treated with any of the following medications, dosing must be stable for 30 days prior to Visit 1 Screen. Patient must agree to maintain the same dose of medication throughout the study:
• Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs).
• Bile acid sequestrants such as colestipol, cholestyramine and colesevelam.
• Participants must use one highly effective method of contraception for 30 days before the study through 90 days after study completion for males and through 30 days after study completion for females. Highly effective methods of contraception include: Oral, implantable, transdermal or injectable hormonal contraceptives; standard intrauterine device or vaginal ring; Male or female condoms and diaphragms used with spermicide; abstinence from heterosexual intercourse; female partners exclusively sexually active with a surgically sterilized male partner. Females who are surgically sterile having experienced a prior hysterectomy, bilateral salpingectomy, or bilateral oophorectomy or postmenopausal (defined as12 consecutive months with no menses) are not considered to be of childbearing potential.

You may not qualify if:

• Pregnant or lactating
• Structural or metabolic diseases/conditions that affect the gastrointestinal system
• Use of the following medications at least 14 days prior to Visit 1 throughout the duration of the treatment period
• Patients may elect to withdraw from bile acid sequestrants such as colestipol, cholestyramine and colesevelam or they may continue but they must continue at the same dose throughout the study.
• GI medications including:
• Anti-nausea agents including trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine
• Osmotic laxative agents including lactulose, sorbitol or PEG solutions as Miralax and Glycolax
• Prokinetic agents including tegaserod, metoclopramide, prucalopride, domperidone, erythromycin, clarithromycin and azithromycin.
• HT3 antagonists including alosetron, ondansetron, tropisetron
• Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors including tegaserod, ondansetron, granisetron and tropisetron
• All narcotics including codeine, morphine, and propoxyphene, either alone or in combination
• Anti-cholinergics including dicyclomine, hyoscyamine, propantheline.
• Antimuscarinics
• Tramadol
• Peppermint oil

Sponsors & Collaborators

• Michael Camilleri, MD: lead
• NGM Biopharmaceuticals, Inc: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

aldafermin

Results Point of Contact

• Title: Michael Camilleri, M.D., D.Sc.
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-284-2687

Study Officials

• Michael Camilleri, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 30 participants with diarrhea and laboratory confirmed BAM will be randomized 1:1 to either aldafermin (NGM282), 1 mg, or placebo given daily by subcutaneous injection. Participants and investigators are blinded to the treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Pharmacology and Physiology, Atherton and Winifred W. Bean Professor, College of Medicine, Consultant, Division of Gastroenterology and Hepatology.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 22, 2021
• Study Start: December 1, 2021
• Primary Completion: November 8, 2022
• Study Completion: November 8, 2022
• Last Updated: October 12, 2023
• Results First Posted: October 12, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)