Charcot-Marie-Tooth DiseasePhase 2NCT03124459
Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
A Phase 2 study testing ACE-083 in people with Charcot-Marie-Tooth Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 16 sites in United States.
Trial summary
This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (CMT1 and CMTX), to be conducted in two parts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Charcot-Marie-Tooth Disease
- What is being tested?
- ACE-083
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 16 sitesUnited States
- Study dates
- 31 Jul 2017to 11 Mar 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Diagnosis of CMT1 or CMTX confirmed by:
- Clinical presentation and electrodiagnostics
- Genetically-confirmed CMT1 or CMTX for the patient or first-degree relative
- Part 1:
- Six-minute walk distance (6MWD) of at least 150 meters (without a brace or walker)
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- Independent ambulation for at least 10 meters, without a brace
- Left and right ankle plantar flexion MRC grade 4+ to 5, inclusive
- Part 2:
- 6MWD ≥ 150 and ≤ 500 meters (without a brace or walker); a maximum of 20% of enrolled patients with 6MWD ≥ 450 meters will be included
- Left and right ankle plantar flexion MRC grade 4- to 5, inclusive
- Left and right ankle dorsiflexion Medical Research Council (MRC) manual muscle testing (MMT) grade 3 to 4+ inclusive. No more than 12 of the 40 subjects may have a grade of 3 or 3+ on one or both sides.
- Females of childbearing potential must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods during study participation and for 8 weeks following the last dose of ACE-083. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if he has undergone a successful vasectomy.
- Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
- Signed written informed consent
Who cannot join
- History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- Symptomatic cardiopulmonary disease, significant functional impairment, significant orthopedic or neuropathic pain, or other co morbidities that in the opinion of the investigator would limit a patient's ability to complete strength and/or functional assessments on study
- Type 1 or type 2 diabetes mellitus
- Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study
- Renal impairment (serum creatinine ≥ 2 times the upper limit of normal (ULN])
- Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
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- Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of any anticoagulation/platelet modifying therapies up to 2 weeks prior to Study Day 1 and for duration of study; low dose aspirin [≤ 100 mg daily] is permitted)
- Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength
- Major surgery within 4 weeks prior to Study Day 1
- Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for duration of study; intra-articular/topical/inhaled/intranasal physiologic doses of systemic corticosteroids are permitted
- Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted
- Any change in medications potentially affecting muscle strength or function within 4 weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic beta-adrenergic agonists)
- Previous exposure to any investigational agent potentially affecting muscle volume, muscle strength, or muscle or nerve function within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks prior to Study Day 1 if half-life is unknown)
- Any previous or current exposure to ACE-083
- Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study
- Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the lower leg, as applicable (e.g., knee/hip replacement metallic implants)
- Known active substance abuse, including alcohol
- History of sensitivity to protein pharmaceuticals
- Female that is lactating/breast-feeding
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
University of Colorado
Aurora, Colorado, 80045
University of Vermont
Burlington, Vermont, 05401
Carolinas Healthcare System Neurosciences Institute
Charlotte, North Carolina, 28203
University of Florida
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Kansas Medical Center - Neurology Department
Kansas City, Kansas, 66160
University of Minnesota, Neurology Department
Minneapolis, Minnesota, 55455
Columbia University
New York, New York, 10032
University of California-Irvine
Orange, California, 92868
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Rochester Medical Center, Neurology
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X
This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (CMT1 and CMTX), to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.
Read the detailed description
Part 1 (non-randomized, open-label, dose-escalation)
Part 1 will consist of up to 3 cohorts of 6 patients each and will evaluate multiple ascending dose levels of ACE-083 administered bilaterally once every 3 weeks for up to 5 doses in the tibialis anterior (TA) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment.
Part 2 (randomized, double-blind, placebo-controlled) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted by the Safety Review Team (SRT) to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 40 new patients may be enrolled and randomized (1:1 randomization) to receive either ACE 083 (n=20) or placebo (n=20) bilaterally by injection into both TA muscles once every 3 weeks for up to 17 doses.
Study duration for Parts 1 and 2 for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.
Study duration for Part 2 will be 15 months, including 4-week screening, 6 months double blind placebo-controlled, 6 months open-label and 8 week follow-up.
- Conditions
- Charcot-Marie-Tooth Disease
- Being tested
- ACE-083, Placebo
- Keywords
- CMT1 / CMTX
- Medical subject headings
- Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth disease, X-linked, 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE-083Drug
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.
PlaceboDrug
Recombinant fusion protein or buffer solution
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Cohort 1 | Experimental | ACE-083 150 mg intramuscular (IM) (tibialis anterior muscle), once every 3 weeks for up to 5 doses. Receives: Drug: ACE-083 |
| Part 1 Cohort 2 | Experimental | ACE-083 200 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses. Receives: Drug: ACE-083 |
| Part 1 Cohort 3 | Experimental | ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses. Receives: Drug: ACE-083 |
| Part 2 (double-blind placebo controlled) | Experimental | ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses Receives: Drug: ACE-083; Drug: Placebo |
| Part 2 (open label) | Experimental | ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 8 doses Receives: Drug: ACE-083 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Frequency of Adverse Events
Number of subjects with at least one adverse event related to treatment intervention from Part 1 of this study. Since this outcome measure was only pre-specified for Part 1, only data from the Part 1 participants is reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).
Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study.
The percent change from baseline in volume of injected muscle, by MRI compared to the Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Secondary outcomes (9)
Part 2: Absolute Change in Amount of Intramuscular Fat Tissue to the End of the Double-blind Placebo-controlled Portion of the Study
The absolute change from baseline in intramuscular fat fraction of the injected muscle, by MRI compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Strength to the End of the Double-blind Placebo-controlled Portion of the Study
Percent change from baseline in strength of the injected muscle, by Quantitative Muscle Testing (QMT) compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Function - Walk/Run Time to the End of the Double-blind Placebo-controlled Portion of the Study
The percent change from baseline in functional assessments, as measured by 10-meter walk/run time when compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Function - Walk Distance Assessed at the End of the Double-blind Placebo-controlled Portion of the Study
Percent change from baseline in functional assessments, as measured by 6-minute walk distance when compared to Day 190 Assessment, is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period for the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Balance and Fall Risk at the End of the Double-blind Placebo-controlled Portion of the Study.
Change from baseline in static and dynamic balance, as measured by the Berg Balance Scale, a 14-item scoring system to assess balance and fall risk in adults. The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function. Total scores are used for reporting, with a range of 0-56, with higher scores mean a better demonstration of function. A score of 56 indicates functional balance. A score of < 45 indicates individuals may be at greater risk of falling. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Balance and Fall Risk From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
Percent change was calculated for the difference from baseline and Day 190 Assessment scores on the Berg Balance Scale. The Berg Balance Scale, is a 14-item scoring system to assess balance and fall risk in adults. The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function. Total scores are used for reporting, with a range of 0-56, with higher scores mean a better demonstration of function. A score of 56 indicates functional balance. A score of < 45 indicates individuals may be at greater risk of falling. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Clinical Examination Score From Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Change from baseline in the Charcot-Marie-Tooth (CMT) Examination Score, version 2 (CMTES2), a composite scoring system to assess sensory and motor impairment in subjects with CMT. The total score is a subset of the following items from the CMT neuropathy score instrument: Sensory symptoms, Motor symptoms (legs), Motor symptoms (arms), Pinprick Sensibility, Vibration, Strength (legs), and Strength (arms). Each individual item is assessed using a rating from 0 to 4 inclusive. The range of CMTES2 scores is from 0 to 28 inclusive. A higher score means a greater degree of symptom severity. The Baseline score and score on the Day 190 Assessment are reported. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Clinical Examination Score in Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Percent change was calculated for the difference in the Charcot-Marie-Tooth (CMT) Examination Score (CMTES2) from baseline and Day 190 Assessment scores. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Patient-reported Quality of Life From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
The absolute change from baseline in Charcot-Marie-Tooth Health Index (CMT-HI), a disease-specific, patient-reported health index score from baseline and Day 190 Assessment scores. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.
Measured: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start31 Jul 2017
- Primary completion11 Mar 2020
- Study completion11 Mar 2020
Why it stopped: (Investigation of ACE-083 for use in patients with CMT is being discontinued as it did not achieve functional secondary endpoints in the A083-03 trial.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Charcot-Marie-Tooth DiseaseStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jay Backstrom, MD, Study chair, Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03124459
- Sponsor's protocol ID
- A083-03
- Other IDs
- ACE-083
- Status last verified
- Sep 2022
- First submitted
- 12 Apr 2017
- Last updated
- 26 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Thomas FP, Brannagan TH 3rd, Butterfield RJ, Desai U, Habib AA, Herrmann DN, Eichinger KJ, Johnson NE, Karam C, Pestronk A, Quinn C, Shy ME, Statland JM, Subramony SH, Walk D, Stevens-Favorite K, Miller B, Leneus A, Fowler M, van de Rijn M, Attie KM. Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease. Neurology. 2022 Jun 6;98(23):e2356-e2367. doi: 10.1212/WNL.0000000000200325.
PubMed 35545446
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X
- ClinicalTrials.gov ID
- NCT03124459
- Acronym / sponsor ID
- A083-03
- Conditions
- Charcot-Marie-Tooth Disease
- Keywords
- CMT1 / CMTX
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: (Investigation of ACE-083 for use in patients with CMT is being discontinued as it did not achieve functional secondary endpoints in the A083-03 trial.
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2017 (actual)
- Primary completion
- 11 Mar 2020 (actual)
- Study completion
- 11 Mar 2020 (actual)
- First posted
- 21 Apr 2017 (actual)
- Results
- Posted 28 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (CMT1 and CMTX), to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.
Detailed description
Part 1 (non-randomized, open-label, dose-escalation)
Part 1 will consist of up to 3 cohorts of 6 patients each and will evaluate multiple ascending dose levels of ACE-083 administered bilaterally once every 3 weeks for up to 5 doses in the tibialis anterior (TA) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment.
Part 2 (randomized, double-blind, placebo-controlled) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted by the Safety Review Team (SRT) to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 40 new patients may be enrolled and randomized (1:1 randomization) to receive either ACE 083 (n=20) or placebo (n=20) bilaterally by injection into both TA muscles once every 3 weeks for up to 17 doses.
Study duration for Parts 1 and 2 for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.
Study duration for Part 2 will be 15 months, including 4-week screening, 6 months double blind placebo-controlled, 6 months open-label and 8 week follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1 Cohort 1 | Experimental | Drug: ACE-083ACE-083 150 mg intramuscular (IM) (tibialis anterior muscle), once every 3 weeks for up to 5 doses. |
| Part 1 Cohort 2 | Experimental | Drug: ACE-083ACE-083 200 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses. |
| Part 1 Cohort 3 | Experimental | Drug: ACE-083ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses. |
| Part 2 (double-blind placebo controlled) | Experimental | Drug: ACE-083, Drug: PlaceboACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses |
| Part 2 (open label) | Experimental | Drug: ACE-083ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 8 doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 years
- Diagnosis of CMT1 or CMTX confirmed by:
- Part 1:
- Left and right ankle dorsiflexion Medical Research Council (MRC) manual muscle testing (MMT) grade 3 to 4+ inclusive. No more than 12 of the 40 subjects may have a grade of 3 or 3+ on one or both sides.
- Females of childbearing potential must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods during study participation and for 8 weeks following the last dose of ACE-083. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if he has undergone a successful vasectomy.
Key exclusion criteria (19 listed)
- History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- Symptomatic cardiopulmonary disease, significant functional impairment, significant orthopedic or neuropathic pain, or other co morbidities that in the opinion of the investigator would limit a patient's ability to complete strength and/or functional assessments on study
- Type 1 or type 2 diabetes mellitus
- Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study
- Renal impairment (serum creatinine ≥ 2 times the upper limit of normal (ULN])
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 |
|---|---|---|
| ACE-083Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution. | Drug | Part 1 Cohort 1, Part 1 Cohort 2, Part 1 Cohort 3, Part 2 (double-blind placebo controlled), Part 2 (open label) |
| PlaceboRecombinant fusion protein or buffer solution | Drug | Part 2 (double-blind placebo controlled) |
Primary outcome
Part 1: Frequency of Adverse Events
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).
Number of subjects with at least one adverse event related to treatment intervention from Part 1 of this study. Since this outcome measure was only pre-specified for Part 1, only data from the Part 1 participants is reported.
Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study.
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
The percent change from baseline in volume of injected muscle, by MRI compared to the Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
9 secondary outcomes
Part 2: Absolute Change in Amount of Intramuscular Fat Tissue to the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Strength to the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Function - Walk/Run Time to the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Muscle Function - Walk Distance Assessed at the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period for the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Balance and Fall Risk at the End of the Double-blind Placebo-controlled Portion of the Study.
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Balance and Fall Risk From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Clinical Examination Score From Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Percent Change in Clinical Examination Score in Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Part 2: Change in Patient-reported Quality of Life From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35545446Thomas FP, Brannagan TH 3rd, Butterfield RJ, Desai U, Habib AA, Herrmann DN, Eichinger KJ, Johnson NE, Karam C, Pestronk A, Quinn C, Shy ME, Statland JM, Subramony SH, Walk D, Stevens-Favorite K, Miller B, Leneus A, Fowler M, van de Rijn M, Attie KM. Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease. Neurology. 2022 Jun 6;98(23):e2356-e2367. doi: 10.1212/WNL.0000000000200325.
- Individual participant dataSharing planned: Undecided
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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.
Jay Backstrom, MD study chair
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACE-083 in people with Charcot-Marie-Tooth Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 16 sites 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 15 inclusion and 19 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: stopped early, as of the sponsor's last update on 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites 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. 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 28 Jul 2021). 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?
Part 1: Frequency of Adverse Events (time frame: From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).). 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?
On the ClinicalTrials.gov record for NCT03124459, which also lists 1 linked publication.
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 26 Sep 2022.