Chronic DiarrheaPhase 2NCT05130047
Aldafermin (NGM282) for Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)
A Phase 2 study testing Aldafermin in people with Chronic Diarrhea and Irritable Bowel Syndrome With Diarrhea, run by Michael Camilleri, MD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea, Bile Acid Malabsorption
- What is being tested?
- Aldafermin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 8 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- Osmotic laxative agents including lactulose, sorbitol or PEG solutions as Miralax and Glycolax
- Prokinetic agents including tegaserod, metoclopramide, prucalopride, domperidone, erythromycin, clarithromycin and azithromycin.
- 5-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
- Systemic antibiotics and antibiotics directed at colonic flora including rifaximin and metronidazole
- Use of CNS stimulant medications, including methylphenidate, atomoxetine, modafinil, amphetamines or phentermine.
- Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 Screen and throughout the duration of the study
- Any colonic or major abdominal surgery including bariatric surgery, gastric banding, stomach surgery and intestinal or colonic surgery. Procedures such as appendectomy, cholecystectomy, hysterectomy, caesarean section, or polypectomy are allowed as long as they have occurred at least 3 months prior to Visit 1 Screen.
- .History of colorectal cancer, inflammatory bowel disease, diverticulitis, ischemic colitis, microscopic colitis or celiac disease
- History of organic abnormalities of the GI tract, intestinal obstruction, stricture, toxic megacolon, GI perforation, or impaired intestinal circulation.
- Other GI diseases such as GI bleeding or ulcerations
- History of cerebrovascular disease including stroke, TIA, acute coronary syndrome, myocardial infarction or unstable angina
- Clinically significant cardiac history or presence of electrocardiogram (ECG) findings at Visit 1 Screen:
- Abnormal heart rate < 40 or > 100 beats per minute
- QTc interval > 470 milliseconds (ms)
- QRS interval ≥ 110 ms
- PR interval ≥ 220 ms
- Hepatic dysfunction including abnormal serum alanine aminotransferase [ALT] or aspartate transaminase [AST] > 3 × upper limit of normal [ULN]); total direct bilirubin > 2 × ULN, or alkaline phosphatase > 2 × ULN at Visit 1 Screen
- Clinically significant renal insufficiency including serum creatinine > 2.5 mg/dL at Visit 1 Screen
- History of severe head injury or history of seizures
- History of suicide attempt or a hospitalization for a major psychiatric condition within 1 year prior to Visit 1 Screen. At Visit 1 Screen or during the optional remote consent and eligibility review, participants will complete the Hospital Anxiety and Depression questionnaire. If either score for anxiety or depression individually exceeds 8, the score will be discussed. The patient will be and advised whether to participate or whether to see their primary care physician.
- History of alcohol use disorder or substance use disorder within 2 years of Visit 1 Screen.
- Significant history or clinical manifestation of any endocrine, allergic, dermatological, hepatic, renal, hematological, pulmonary, GI, neurological or psychiatric disorder, malignancy (with the exception of treated basal cell carcinomas), or any other condition that would prevent the individual from participating in the study due to risk to the scientific validity of study assessments or to personal well-being of the patient.
- Participated in another clinical study that includes an investigational drug or a biologic therapy within 30 days or 5 half-lives, whichever time period is longer, prior to Visit 1 Screen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo Controlled Trial of Aldafermin (NGM282) for Treatment of Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)
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).
Read the detailed description
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). Thirty patients will receive either aldafermin (NGM282) or placebo, not both. The study includes a 7 to 28-day long prescreen period and a 28-day long treatment period for a maximum study duration of 56 days. Bowel pattern will be assessed by patient-recorded daily bowel pattern diaries. Serum 7-alpha C4 (C4) and fibroblast growth factor 19 (FGF-19) and fecal bile acids will be measured at baseline and Day 14 and Day 28 of treatment. Safety will be assessed through regular monitoring of adverse events, clinical laboratory results, 12-lead ECGs, physical examinations, and vital signs.
- Conditions
- Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea, Bile Acid Malabsorption, Bile Acid Diarrhea, Bile Acid Malabsorption Syndrome Type II, Functional Diarrhea
- Being tested
- Aldafermin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AldaferminDrug
Also called NGM282
1 mg solution
PlaceboDrug
Aldafermin placebo solution
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fasting Serum C4 Levels
Fasting serum C4 is measured by liquid chromatography-mass spectrometry.
Measured: 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.
Measured: Baseline, 28 days
Secondary outcomes (7)
Stool Consistency
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.
Measured: 14 days, 28 days
Abdominal Pain Score
Abdominal pain rated by patient using an 11-point scale, 0 to 10 inclusive with 0 as none and 10 as worst imaginable abdominal pain.
Measured: baseline, 28 days
Bowel Movements
The total number of bowel movements per day reported by the participant in the daily bowel pattern diary.
Measured: baseline, 28 days
Proportion of Fecal Secretory (CDCA + DCA) Bile Acid as Measured in a Random Stool Sample by a Validated Laboratory Assay.
Fecal secretory bile acids are expressed as a percentage of the total bile acids as measured by high performance liquid chromatography-mass spectrometry.
Measured: 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.
Fecal primary bile acids are expressed as a percentage of the total bile acids as measured by high performance liquid chromatography-mass spectrometry.
Measured: Baseline,14 days, 28 days
Total Fecal Bile Acid Concentration in a Random Stool Sample as Measured by a Validated Laboratory Assay.
Total fecal bile acids concentration in micromoles of bile acid per gram stool as measured by high performance liquid chromatography-mass spectrometry.
Measured: baseline,14 days, 28 days
Total Aldafermin Concentration in Serum as Measured by a Validated Laboratory Assay
Validated aldafermin concentration (PK) laboratory assay
Measured: baseline, 14 days, 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2021
- Study start1 Dec 2021
- Primary completion8 Nov 2022
- Study completion8 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Camilleri, MD
- Sponsor type
- University, hospital or other
- Collaborators
- NGM Biopharmaceuticals, Inc
- Responsible party
- Sponsor-investigator, Michael Camilleri, MD, Mayo Clinic
- Investigators
- Michael Camilleri, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05130047
- Sponsor's protocol ID
- 21-009348
- Status last verified
- Sep 2023
- First submitted
- 10 Nov 2021
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo Controlled Trial of Aldafermin (NGM282) for Treatment of Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)
- ClinicalTrials.gov ID
- NCT05130047
- Acronym / sponsor ID
- 21-009348
- Conditions
- Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea, Bile Acid Malabsorption, Bile Acid Diarrhea, Bile Acid Malabsorption Syndrome Type II, Functional Diarrhea
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Michael Camilleri, MDUniversity, hospital or other
- Collaborators
- NGM Biopharmaceuticals, Inc
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 8 Nov 2022 (actual)
- Study completion
- 8 Nov 2022 (actual)
- First posted
- 22 Nov 2021 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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). Thirty patients will receive either aldafermin (NGM282) or placebo, not both. The study includes a 7 to 28-day long prescreen period and a 28-day long treatment period for a maximum study duration of 56 days. Bowel pattern will be assessed by patient-recorded daily bowel pattern diaries. Serum 7-alpha C4 (C4) and fibroblast growth factor 19 (FGF-19) and fecal bile acids will be measured at baseline and Day 14 and Day 28 of treatment. Safety will be assessed through regular monitoring of adverse events, clinical laboratory results, 12-lead ECGs, physical examinations, and vital signs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aldafermin (NGM282) | Experimental | Drug: AldaferminAldafermin (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. |
| Placebo | Placebo comparator | Drug: PlaceboA 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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
Key exclusion criteria (35 listed)
- 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
- Use of CNS stimulant medications, including methylphenidate, atomoxetine, modafinil, amphetamines or phentermine.
- Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 Screen and throughout the duration of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AldaferminAlso: NGM2821 mg solution | Drug | Aldafermin (NGM282) |
| PlaceboAldafermin placebo solution | Drug | Placebo |
Primary outcome
Fasting Serum C4 Levels
Time frame: 28 days
Fasting serum C4 is measured by liquid chromatography-mass spectrometry.
Change in Stool Consistency From Baseline to Day 28
Time frame: Baseline, 28 days
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.
7 secondary outcomes
Stool Consistency
Time frame: 14 days, 28 days
Abdominal Pain Score
Time frame: baseline, 28 days
Bowel Movements
Time frame: baseline, 28 days
Proportion of Fecal Secretory (CDCA + DCA) Bile Acid as Measured in a Random Stool Sample by a Validated Laboratory Assay.
Time frame: 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.
Time frame: Baseline,14 days, 28 days
Total Fecal Bile Acid Concentration in a Random Stool Sample as Measured by a Validated Laboratory Assay.
Time frame: baseline,14 days, 28 days
Total Aldafermin Concentration in Serum as Measured by a Validated Laboratory Assay
Time frame: baseline, 14 days, 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Camilleri, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aldafermin in people with Chronic Diarrhea and Irritable Bowel Syndrome With Diarrhea, run by Michael Camilleri, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fasting Serum C4 Levels (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.