Safety and Efficacy Study of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-I/rhIGFBP-3) In Myotonic Dystrophy Type 1

Participants were administered 75 grams (g) glucose solution prior to administration of the first dose of IPlex™ and after administration of the last dose. A 2-hour oral glucose tolerance test (OGTT) was performed under fasted conditions.

Time frame: Baseline - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution; Week 24 - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

Participants were administered 75 g glucose solution prior to administration of the first dose of IPLEX™ and after administration of the last dose. A 2-hour OGTT was performed under fasted conditions.

Time frame: Baseline - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution; Week 24 - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The BPI contains 15 questions that assess the severity of pain and its impact or interference on functions of daily life. Pain interference is measured as the mean of 7 items on an 11-point scale where 0 indicates no interference and 10 indicates complete interference. A higher score indicates greater impairment due to pain. Change from baseline scores were measured where a positive change from baseline indicates a worsening of interference due to pain.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The BPI contains 15 questions that assess the severity of pain and its impact or interference on functions of daily life. Pain severity was measured as the mean of 7 items of the questionnaire on an 11-point scale where 0 indicates no pain and 10 indicates the worst pain. A higher score indicates greater pain. Categories assessed include worst pain in 24 hours and average pain. Change from baseline scores were measured where a positive change from baseline indicates a worsening in pain.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The number of steps taken per day was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a negative change from baseline indicates a decrease in the number of daily steps.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The GSFQ contains 6 questions that assess the frequency of certain GERD symptoms and their impact on daily life. Scores were converted and reported out of 100 with higher scores indicative of more frequent and intense GERD symptoms. Change from baseline scores were measured where a negative change from baseline indicates less frequent and intense GERD symptoms.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The GSRS-IBS has 13 questions aimed at identifying the frequency and intensity of IBS symptoms during the past week. Answers are given a score from 1 (no discomfort at all) to 7 (very severe discomfort). A total score was calculated and ranged from 0 to 78. A lower score indicates less discomfort from IBS symptoms. Change from baseline scores were measured where a positive change from baseline indicates increased discomfort from IBS symptoms.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The ISI-Matsuda is based on the average glucose and insulin values obtained during the entire oral glucose tolerance test and are calculated using the following equation: ISI = 10,000 / √ \[ fasting glucose (mg/dL) x fasting insulin(uU/mL) x mean glucose x mean insulin \]

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The LNS test from the Welchsler Adult Intelligence Scale-III was used to assess working memory. The test required that participants recall, in order, numbers and letters presented in an unordered sequence. The number of items is 21. With each item being marked 0 if reported incorrectly or 1 if reported correctly, the maximum score is 21. Raw scores were converted into T-scores using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.

Time frame: Baseline and Week 24

Population: Intention to treat (ITT) population: all enrolled participants who had at least one dose of IPLEX™ or placebo and had at least one post-baseline efficacy assessment. Only participants with data available for analysis are reported.

The MMT was used to assess muscle strength in the distal muscles and the proximal muscles. Distal muscles assessments included wrist extension, wrist flexion, ankle dorsiflexion and plantarflexion. Proximal muscle assessments included shoulder abduction, elbow extension, elbow flexion, hip extension, hip abduction, hip flexion, knee extension and knee flexion. In MMT, each muscle assessment was given a score of 0 to 5, where 0 indicated 'no contraction palpable' and 5 indicated 'normal strength'. The scores from each muscle were summed and the maximum overall score of all measured muscles was 140, the maximum distal score was 40 and the maximum proximal score was 80. Higher scores indicated higher muscle strength. Change from baseline scores were measured where a positive change from baseline indicates an improvement in muscle strength.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The Purdue Pegboard Test consists of a board with two sets of 25 holes, 4 concave cups, and a number of small metal pins. Participants were required to pick up the pins from a holder and place them in the holes as quickly as possible over 30 seconds with their dominant hand. The score was calculated as the number of pins placed into holes in 30 seconds and was measured at baseline and Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of pins placed in the board.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The QUICKI is based on fasting glucose and insulin measurements and are calculated using the following equation: QUICKI = 1/\[ log(fasting glucose in mg/dL) + log (fasting insulin in uU/mL) \]

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The Rey Complex Figure Test (RCFT) assesses visuospatial construction ability and visual memory through four different tests: copy (copying a complex geometric figure), immediate recall of the figure (drawing figure from memory at 3 minutes), delayed recall (drawing figure at 30 minutes after initial copy), and recognition score (selecting individual parts of the figure from sketches provided). Copy performances are divided into 18 components with a maximum score of 2 each. The maximum score for each figure is 36.

Time frame: Baseline and Week 24

Population: Modified Per Protocol Population

The Selective Reminding Test measures verbal learning and memory and involves remembering a verbal list of 12 words. Participants were required to recall the 12 words presented. Words that were missed on recall were presented again, and the process is repeated until all 12 words were correctly recalled. The cued recall scores ranged from 0-11 and multiple choice recognition scores ranged from 0-12. Change from baseline scores were measured where a positive change from baseline indicates an improvement in verbal recall and memory.

Time frame: Baseline and Week 24

Population: Modified Per Protocol Population

The Selective Reminding Test measures verbal learning and memory and involves remembering a verbal list of 12 words. Participants were required to recall the 12 words presented. Words that were missed on recall were presented again, and the process was repeated until all 12 words were correctly recalled. The total word list recall and delayed recall were calculated as T-scores. Raw scores were converted to T-score using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.

Time frame: Baseline and Week 24

Population: Modified Per Protocol Population:

The SF-36 is a 36-item questionnaire that evaluates quality of life through physical and mental health across eight scales, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Change from baseline scores were measured where a positive change from baseline indicates an improvement in quality of life.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The SDQ had 15 questions relating to the oral phase and pharyngeal phase of swallowing. Answers for 14 questions were assigned a number (0-3) based on a 4-point verbal scale (never, seldom, frequently, very frequently) and the last question was a yes or no question about respiratory infections. A higher score is indicative of greater swallowing issues with 44.5 as the highest possible score. A total score of ≥ 11 suggests impairment. Change from baseline scores were measured where a positive change from baseline indicates increased swallowing impairment.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

Change from baseline scores were measured where a negative change from baseline indicates less time spent inactive.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The Stroop Color Word Test measures selective attention and cognitive flexibility. The test has three parts, the Word test (reading words), the Color test (naming the ink color in which words are displayed) and the Color-Word test (saying the ink color not reading the word). An interference score was calculated from the Color, Word and Color-Word scores and is an indication of how well a person can complete a task while disregarding interfering information. Raw scores were converted into T-scores using available normative data. Scores range from 0 to 100. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.

Time frame: Baseline and Week 24

Population: Modified Per Protocol Population

Participants were timed on their ability to climb up 4 stairs and timed separately to climb down 4 stairs at baseline and at week 24. The stairs were free-standing or the same flight of stairs was used at each assessment. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the time taken for paticipants to ascend or descend 4 stairs.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

Participants were timed on their ability to travel 30 feet on the same surface at each assessment at baseline and at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the time taken to travel 30 feet.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

A negative change from baseline indicates a decrease in total blood cholesterol level.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

A negative change from baseline indicates a decrease in total blood HDL level.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

A positive change from baseline indicates an increase in total blood LDL level.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

A negative change from baseline indicates a decrease in total blood triglycerides level.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The TMT assesses executive function, sequencing, mental flexibility, visual spanning speed and motor function. In TMT Part A, the participant had to draw lines in the correct order between 25 numbers randomly arranged on the page. In TMT Part B, the participant had to draw lines between 25 numbers and letters in alternating order (e.g., 1-A-2-B...etc). Times for Part A and Part B were used to derive T-scores which can range from a minimum of 0 and a maximum of 100. Raw scores were converted into T-scores using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.

Time frame: Baseline and Week 24

Population: Modified Per Protocol Population

The 6MWT measured the distance in meters that participants were able to walk over a total of six minutes. After a 10 minute resting period, the participants completed the 6MWT on a hard, flat surface at baseline and at Week 24.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression. Lower scores indicate no or minimal depression, with a maximum total score of 63.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The peak activity index measures the number of steps walked in the 30 minutes of fastest walking that occurred in a 24 hour period. This was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of steps walked during the 30 minute period of fastest walking.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.

The sustained activity index measures the highest number of steps sustained over a continuous 20 minute period. This was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of steps walked over 20 minutes of activity.

Time frame: Baseline and Week 24

Population: Per protocol (PP) population: all enrolled participants who were at least 80% compliant with study dosing, had no more than 21 days interruption in therapy at any one time, had efficacy assessments required at the Week 24 study visit, met all inclusion and exclusion criteria, and were not major protocol violators. Only participants with data available for analysis are reported.